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Research
The Department
of Biostatistics maintains an active research program both in the
development of new statistical methodology and in the collaboration
on important research projects in public health and the biomedical
area. Since 1995 the faculty in the Department have co-authored
more than 600 publications in a variety of research areas. This
includes papers in statistical methodology, as well as collaborative
research papers in the areas of cancer treatment and prevention,
cardiovascular disease, transplantation, AIDS, childhood disease,
health services and outcomes research, evaluation of diagnostic imaging systems and evaluation of treatment
for psychiatric problems. Currently members of the Department are
responsible for the statistical analysis of more than 100 million
dollars of funding to conduct research in the public health and
biomedical areas.
The Department
of Biostatistics is nationally and internationally recognized for
its contributions to the investigation of public health concerns
associated with urban and industrial environments. These efforts
are exemplified by the department's research into the evaluation
of disease risk among workers exposed to potentially toxic substances.
To date, large-scale follow-up studies have evaluated the health
risks of more than 250,000 workers in a wide variety of industries
including steel, coal mining, automobile manufacturing, chemical,
fiberglass, nickel, and pharmaceutical. The methodologic approaches
developed in these studies have served as models for national and
international investigations involving large-scale occupational
cohorts. Biostatistics faculty have also contributed to environmental
quantitative risk assessment, emphasizing the use of statistical
models to quantify cancer risks and the development of methodologies
to facilitate the use of epidemiologic data for setting environmental
standards. Statistical models developed by faculty members within
the department include improved models for carcinogenesis, models
to estimate reproductive risk and models to predict carcinogenicity
of chemicals. Faculty members have developed a software package,
the Occupational Cohort Mortality Analysis Program (OCMAP), that
is used as a primary analytic tool for statistical/epidemiological
research by over 300 institutions in the US and abroad. They also
developed a large data base repository and retrieval system for
detailed mortality data provided by the National Center for Health
Statistics and the U.S. Census Bureau, called the Mortality and
Population Data System (MPDS). MPDS is used regularly by the Department
and outside researchers as a unique source of standard population
data for comparative mortality analyses with OCMAP or other software.
Departmental faculty
collaborate closely with the faculty in other GSPH departments as
well as with various departments within the School of Medicine,
the Pittsburgh Cancer Institute, and the VA Pittsburgh Healthcare System. Since 1975 faculty from the
Department have directed the Biostatistical Center and provided
biostatistical expertise for the National Surgical Adjuvant Breast
and Bowel Project (NSABP). The NSABP is an internationally recognized,
multidisciplinary, clinical trial research organization. The physicians
and their support personnel are affiliated with major medical centers,
community hospitals, and physician groups in 49 states and in 6
Canadian provinces. Since 1971, the NSABP has enrolled more than
100,000 participants in over 50 large-scale, community-based randomized
clinical trials that are designed to assess treatments for breast
and colorectal cancers. The Biostatistical Center is the statistical
and data management coordinating center for all the NSABP treatment
trials. The Center is responsible for the statistical aspects of
protocol design and implementation, centralized randomization, data
collection and management of patient treatment and follow-up information,
and analysis of study results. The NSABP Biostatistical Center is
also the statistical and data management coordinating center for
the Breast Cancer Prevention Trial, a randomized double-blinded
trial of 13,000 women at increased risk of breast cancer. The primary
aim of this trial was to test the worth of the oral drug, tamoxifen,
as a preventive for breast cancer. The trial demonstrated that tamoxifen
resulted in a 50% reduction in breast cancer incidence. Recently
the NSABP completed accrual of over 19,000 women into the STAR Trial which randomized
women at high risk for breast cancer to receive either tamoxifen
or raloxifene as chemotherapy to reduce their risk of developing breast cancer. The goal of this study is to determine if raloxifene will be as effective as tamoxifen in reducing breast cancer risk with the additional benefit of having fewer side effects than tamoxifen. It is anticipated that the final results of this trial will be available by the Spring of 2006.
Additional collaborative
research in which the department supplies the quantitative component
include evaluation of diagnostic imaging systems, evaluation of
the etiology and treatment of ear disease in children, evaluation
of treatment and survival of patients with organ transplants, development
of learning tools to study tumor growth and evaluation of treatment
for psychiatric patients. In addition to collaborative research
the department is active in the development of new statistical methodology.
The current faculty has more than 150 publications related to the
development of new statistical methodology or innovative improvements
in the design of biomedical studies. Active areas of methodological
research include survey research, exploratory data analysis, survival analysis, missing data analysis, copulas,
ROC analysis, sequential analysis and designs, case cohort studies
and statistical genetics. More information on specific types of
research areas in which the department is involved can be found
under the categories listed below. Select a category or scroll
through this document.
NSABP - Breast Cancer Treatment
The Biostatistics
Department began collaboration with the National Surgical Adjuvant
Breast and Bowel Project (NSABP) in 1974. Since that time there
have been more than 50,000 breast cancer patients randomized to
one of more than 40 clinical trials to evaluate various treatment
modalities for women with Stage I and Stage II breast cancer. Treatment
modalities evaluated in these trials include chemotherapy, radiation,
immunotherapy and hormonal therapy, as well as differing surgical
procedures. The NSABP is internationally recognized as one of the
premier clinical trials groups in the evaluation of new treatments
for women with operable breast cancer. Notable accomplishments by
the NSABP and in which members of the Biostatistics Department provided
the primary statistical analysis include being one of the first
two groups to demonstrate the efficacy of chemotherapy in the treatment
of women with Stage II breast cancer (Protocol B-05), one of the
first groups to demonstrate the equivalence in terms of survival
of patients receiving more conservative surgery to those receiving
more aggressive surgery (Protocols B-04, B-06), the first group
to demonstrate the efficacy of tamoxifen in addition to chemotherapy
for patients with Stage II breast cancer (Protocol B-09), and among
the first groups to demonstrate the efficacy of chemotherapy for
Stage I breast cancer patients with negative nodes who are estrogen
receptor negative (Protocol B-13) and the efficacy of tamoxifen
alone for Stage I breast cancer patients with positive nodes who
are estrogen receptor positive (Protocol B-14). The observation
in Protocol B-14 that tamoxifen reduced the incidence of cancer
recurrence in the opposite breast was one of the major factors leading
to the evaluation and subsequent demonstration of efficacy of tamoxifen
as a prophylactic for breast cancer treatment.
The finding that
even negative node patients benefit from more aggressive treatment
and animal experiments suggesting that surgery may accelerate metastasis
led NSABP to consider protocols where chemotherapy was given prior
to surgery. Protocol B-18 demonstrated that preoperative chemotherapy
results in the same survival as postoperative chemotherapy but often
results in more conservative surgery.
Selected Publications:
Swain SM, Wilson JW, Mamounas EP, Bryant J, Wickerham DL, Fisher B, Paik S, Wolmark N. Estrogen receptor status of the primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer. Journal of the National Cancer Institute, 96:516-523, 2004.
Bear HD, Anderson
S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret
H, Soran A, Wickerham DL and Wolmark N. The Effect on Tumor Response
of Adding Sequential Preoperative Docetaxel (Taxotere) to Preoperative
Doxorubicin and Cyclophosphamide (AC): Preliminary Results from
National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol
B-27. Journal of Clinical Oncology, 21:4165-4174, 2003.
Jeong J,
Jung S, Wieand S. A parametric model for long-term follow-up
data from phase III breast cancer clinical trials. Statist
Med, 22:339-352, 2003.
Smith RE, Bryant
J, DeCillis A, and Anderson S. Acute myeloid leukemia
and myelodysplastic syndrome following doxorubicin-cyclophosphamide
adjuvant therapy for operable breast cancer: The NSABP experience.
Journal of Clinical Oncology, 21(7), 1195-1204, 2003.
Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, Margolese RG, Wolmark N. Tamoxifen, Radiation Therapy or Both for Prevention of Ipsliateral Breast Tumor Recurrence After Lumpectomy in Women with Invasive Breast Cancers of Less Than or Equal 1 cm. Journal of Clinical Oncology, 20:4141-4149, 2002.
Fisher ER, Wang J, Bryant J, Fisher B, Mamounas E, Wolmark N. Pathobiology of preoperative chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18. Cancer, 95:681-695, 2002.
Costantino JP.
The impact of Hormonal treatment on quality of life of patients
with metastatic breast cancer. Clin Therapeutics 24; Suppl
C:26-42, 2002.
Smith RE, Anderson
SJ, Brown A, Scholnik AP, Desai AM, Kardinal CG, Lembersky
BC, and Mamounas EP. Phase II trial of a doxorubicin, docetaxel,
and cyclophosphamide triplet for locally advanced and metastatic
breast cancer: results from NSABP trial BP-58. Clinical Breast
Cancer, 3(5), 333-340, 2002
Fisher B, Anderson
S, Bryant J, Margolese RG, Deutsch J, Fisher ER, Jeong
JH and Wolmark N. Twenty-year follow-up of a randomized trial
comparing total mastectomy, lumpectomy, and lumpectomy followed
by irradiation for the treatment of invasive breast cancer. The
New England Journal of Medicine, 347(16), 1233-1241, 2002.
Fisher B, Jeong
JH, Anderson S, Bryant J, Fisher ER and Wolmark
N. Twenty-five-year follow-up of a randomized trial comparing
radical mastectomy, and total mastectomy followed by irradiation.
The New England Journal of Medicine, 347(8), 567-575, 2002.
Paik S, Bryant
J, Tan-Chiu E, Romond E, Park K, Browm A, Yother G, Anderson
S, Smith R, Wickerham DL, Wolmark N. Real World Performance
of HER2 Testing - National Surgical Adjuvant Breast and Bowel
Project Experience. J Natl Cancer Inst, (94):852-854, 2002.
Singletary
SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, Borgen
PI, Clark G, Edge SB, Hayes DF, Hughes LL, Hutter RVP, Morrow
M, Page DL, Recht A, Theriault RL, Thor A, Weaver DL, Wieand
HS, Greene FL. Revision of the American Joint Committee on
Cancer Staging System for Breast Cancer. J
Clin Oncol, 20:3628-3636, 2002.
Fisher, ER, Anderson,
S, Tan-Chiu, E, Fisher, B, Eaton, L and Wolmark, N Fifteen
year prognostic discriminants for invasive breast cancer: NSABP
Protocol B-06. Cancer, 91(8): 1679-1687, 2001.
Fisher, B, Anderson,
S, Tan-Chiu, E., Wolmark, N, et al. Tamoxifen and chemotherapy
for axillary node negative, estrogen receptor-negative breast
cancer: findings from the National Surgical Breast and Bowel Project
B-23. Journal of Clinical Oncology, 93(4): 931-942, 2001.
Fisher, B, Anderson,
S, Decillis, D, Dimitrov, N, et al. Further evaluation of
intensified and increased total dose of cyclophosphamide for the
treatment of primary breast cancer: findings from National Surgical
Adjuvant Breast and Bowel Project B-25. Journal of Clinical
Oncology, 17(5): 3374-3388, 1999.
Bryant J,
Fisher B, Gunduz N, Costantino JP, Emir B. S-Phase Fraction
Combined with Other Patient and Tumor Characteristics for the
Prognosis of Node-Negative, Estrogen-Receptor Positive Breast
Cancer. Breast Cancer Research and Treatment, 51: 239-253,
1998.
Dignam J, Bryant
J, Wieand HS, Fisher B, Wolmark N. Early Stopping of
a Clinical Trial When There Is Evidence That the Treatment will
Ultimately Not Prove Beneficial: Protocol B-14 of the National
Surgical Adjuvant Breast and Bowel Project. Controlled Clinical
Trials, 19: 575-588, 1998.
Paik S, Bryant
J, Park C, Fisher B, et al. ErbB-2 and Response to Doxorubicin
in Patients with Axially Lymph Node Positive, Hormone Receptor
Negative Breast Cancer. Journal of the National Cancer Institute,
90(18): 1361-70, 1998.
Fisher B, Bryant
J, Wolmark N, Mamounas E, Brown A, Fisher E, Wickerham DL,
Begovic M, DeCillis A, Robidoux A, Margolese R, Cruz A, Hoehn
J, Lees A, Dimitrov N, Bear H. The Effect of Preoperative Chemotherapy
on the Outcome of Women with Operable Breast Cancer. Journal
of Clinical Oncology,16(8): 2672-2685, 1998.
Dignam JJ, Redmond
CK, Fisher B, Costantino JP, Edwards BK. Prognosis
among black women and white women with node-negative breast cancer:
findings from two randomized clinical trials of the national surgical
adjuvant breast and bowel project (NSABP). Cancer 80(1):
80-90, 1997.
Fisher, B, Anderson,
S, Wickerham, DL, Decillis, A, et al. Increased intensification
and increased total dose of cyclophosphamide in a doxorubicin-cyclophosphomide
regimen for the treatment of primary breast cancer: findings from
NSABP B-22. Journal of Clinical Oncology, 15(5): 1858-1869,
1997.
Fisher B, Anderson
S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM:
Reanalysis and results after 12 years of follow-up in a randomized
clinical trial comparing total mastectomy with lumpectomy with
or without irradiation in the treatment of breast cancer.
NEJM 333:1456-61, 1995.
Fisher ER, Anderson
S, Redmond CK et al: Pathologic findings from the National
Surgical Adjuvant Breast Project Protocol B-06: 10-year pathologic
and clinical prognostic discriminants. Cancer 71:2507-2514,
1993.
Fisher ER, Anderson
S, Redmond CK and Fisher B: Ipsilateral breast tumor
recurrence and survival following lumpectomy and irradiation:
Pathologic findings from NSABP Protocol B-06. Seminars in
Surgical Oncology 8:161-166, 1992.
Fisher ER, Costantino
JP, Fisher B, Redmond CK et al: Pathologic findings
from the National Surgical Adjuvant Breast Project (Protocol 4):
Discriminants for 15-year survival. Cancer 71:2142-2150,
1992.
Fisher B, Anderson
S, Redmond CK, Wickerham DL, Wolmark N, Mamounas EP,
Deutsch M and Margolese R: Significance of ipsilateral breast
tumor recurrence after lumpectomy. Lancet 338:327-331,
1991.
Fisher ER, Leeming
R, Anderson S, Redmond CK, Fisher B and collaborating
NSABP investigators: Conservative management of intraductal carcinoma
(DCIS) of the breast. Journal of Surgical Oncology 47:139-147,
1991.
Fisher B,
Redmond CK, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham
DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A,
Foster R, Caplan R and Others: A randomized clinical trial evaluating
sequential methotrexate and fluorouracil in the treatment of patients
with node-negative breast cancer who have estrogen-receptor-negative
tumors. New England Journal of Medicine 320(8):473-478,
1989.
Fisher B, Costantino
JP, Redmond CK, Poisson R, Bowman D, Couture J, Dimitrov
NV, Wolmark DL, Wickerham DL, Fisher ER, Margolese R, Robidoux
A, Shibata H, Terz J, Paterson AHG, Feldman MI, Farrar W, Evans
J, Lickley HL, Ketner M and Others: A randomized clinical trial
evaluating tamoxifen in the treatment of patients with node-negative
breast cancer who have estrogen-receptor-positive tumors.
New England Journal of Medicine 320(8):479-484, 1989.
Fisher B, Bauer
M, Poisson R, Margolese R, Redmond C, et al: Five-Year
results of a randomized clinical trial comparing total mastectomy
and segmental mastectomy with or without radiation in the treatment
of breast cancer. New England Journal of Medicine 312:665-673,
1985.
Fisher B, Redmond
CK, Fisher ER, et al: Ten year results of a randomized clinical
trial comparing radical mastectomy and total mastectomy with or
without radiation. New England Journal of Medicine 312:674-681,
1985.
Redmond CK,
Fisher B, Wieand HS. The methodologic dilemma in retrospectively
correlating the amount of chemotherapy received in adjuvant therapy
protocols with disease free survival: A commentary. Cancer
Treatment Reports 67: 519-526, 1983.
Rockette HE,
Redmond CK, Fisher B, and participating NSABP investigators.
Impact of randomized clinical trials on therapy of primary breast
cancer: The NSABP overview. Controlled Clinical Trials
3:209-225, 1982.
Fisher B, Redmond
C, et al. The treatment of primary breast cancer with chemotherapy
and tamoxifen. N Engl J Med 305:1-6, 1981.
Fisher B, Redmond
CK, Fisher ER, and Participating NSABP Investigators. The
contribution of recent NSABP clinical trials of primary breast
cancer therapy to an understanding of tumor biology - an overview
of findings. Cancer 46:1009-1025, 1980.
Fisher B, Sherman
B, Rockette H, Redmond CK et al. Phenylalanine mustard
(L-PAM) in the management of premenopausal patients with primary
breast cancer: Lack of association of disease-free survival with
depression of ovarian function. Cancer 44:847-857, 1979.
Fisher B, Carbone
P, Economou SG, Frelick R, Glass A, Lerner H, Redmond CK,
Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER: L-phenylalanine
mustard (L-Pam) in the management of primary breast cancer. A
report of early findings. N Engl J Med 292:227-22, 1975.
Fisher ER, Gregorio
R, Redmond CK, Vellios F, Sommers SC, Fisher B: Pathologic
findings from the National Surgical Adjuvant Breast Project (Protocol
No. 4) I. Observations concerning the multicentricity of mammary
cancer. Cancer 35:247-54, 1975.
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NSABP - Colorectal Cancer Treatment Trials
The National Surgical
Breast and Bowel Project (NSABP) began accrual into colo-rectal
cancer trials in 1977. Since the initiation of these trials, faculty
in the Biostatistics Department have been responsible for the data
management and analysis and have participated in the interpretation
and publication of results for these clinical trials. To date more
than 12,000 patients have been randomized to eight colon cancer
trials and four rectal cancer trials. The primary aim of the majority
of these studies was to improve the disease free survival and survival
for colorectal cancer patients undergoing a potentially curable
resection of the colon or rectum. Treatment modalities evaluated
included systemic chemotherapy, portal vein infusion, immunotherapy
and radiation. The NSABP was one of the first groups to demonstrate
that adjuvant chemotherapy could improve disease free survival and
survival for patients with operable colorectal cancer, and one of
the first groups to demonstrate the efficacy of leucovorin-5 FU
as an effective adjuvant therapy. Leucovoren 5FU remains one of
the more effective chemotherapeutic regimens for the treatment of
operable colorectal cancer. The NSABP has also demonstrated in numerous
trials of rectal cancer that radiation as an adjuvant to surgery
controls local disease but does not improve survival.
Selected Publications:
Fisher E, Colangelo
L, Wieand S, Fisher B, Wolmark N. Lack of influence of
cytokeratin-positive nimi micrometastases in "negative node"
patients with colorectal cancer: findings from the NSABP protocols
R-01 and C-01. Diseases of the Colon and Rectum, 46:1021-1025, 2003.
Allegra CJ, Paik
S, Colangelo LH, Parr AL, Kirsch I, Kim G, Klein P, Johnston PG,
Wolmark N, Wieand S. Prognostic value of thymidylate synthase,
Ki-67 and p53 in patients with Dukes' B and C colon cancer: an
NCI-NSABP collaborative study. J Clin Oncol, 21: 241-250,
2003.
Dignam JJ, Ye
Y, Colangelo L, Smith R, Mamounas E, Wieand S, Wolmark
N. Prognosis after rectal cancer in Blacks and Whites participating
in adjuvant therapy randomized trials. J Clin Oncol, 21:413-420,
2003.
Wolmark N, Rockette
H, Mamounas E, Jones J, Wieand S, Wickerham L, Bear
HD, Atkins JN, Dimitrov NV, Glass AG, Fisher ER, Fisher B: A clinical
trial to assess the relative efficacy of 5-FU + leucovorin, 5-FU
+ Levamisole, and 5-FU + Leucovorin + Levamisole in patients with
dukes B and C carcinoma of the colon: Results from NSABP C-04.
J Clin Oncol 17:(11) 3553-3559, Nov 1999.
Wolmark, N.,
Bryant, J., Smith, R., et al. Adjuvant 5-Flourouracil and
Leucovorin With or Without Interferon A 1 fa-2a In Colon Carcinoma:
NSABP Protocol C-05. Journal Natl Cancer Inst 90:1810-1816,
1998.
Hyams DM, Mamounas
EP, Petrelli N, Rockette HE, Jones J, Wieand HS,
Deutsch M, Wickerham DL, Fisher B, Wolmark N: A clinical trial
to evaluate the worth of preoperative multimodality therapy in
patients with operable carcinoma of the rectum: A progress report
of NSABP protocol R-03. Diseases of the Colon and Rectum
40(2): 131-139,1997.
Mayberry RM,
Coates RJ, Hill HA, Click LA, Chen VW, Astin DF, Redmond CK,
et al.: Determinants of Black/White Differences in Colon Cancer
Survival. JNCI, 87(22), 1686-1693, 1995.
Johnston PG,
Fisher ER, Rockette HE, Fisher B, Wolmark N, Drake JC,
Chabner BA and Allegra CJ: The role of thymidylate synthase expression
in prognosis and outcome of adjuvant chemotherapy in patients
with rectal cancer. Journal of Clinical Oncology, Vol.
12, No. 12: 2640-2647, 1994.
Wolmark N, Rockette
HE, Fisher B, Wickerham DL, Redmond CK, Fisher ER,
Jones J, Eleftherios PM, Ore L et al: The benefit of leucovorin-modulated
5-FU as postoperative adjuvant therapy for primary colon cancer:
Results from NSABP protocol C-03. Journal of Clinical Oncology,
Vol. 11, No. 10: 1879-1887, 1993.
Wolmark N,
Rockette HE, Wickerham DL, Fisher B, Redmond CK, Fisher
ER, Potvin M, Darres RJ, Jones J, Robidoux A, Wexler M, Gordon
P, Cruz AB, Horsley S, Nims TA, Thurwell M, Phillips WA, Prager
D, Stern HS, Lerner HJ, Frazier TG: Adjuvant therapy of dukes'
A, B and C adenocarcinoma of the colon with portal vein 5- FU
hepatic infusion: preliminary results of NSABP protocol C0-2.
J Clin Oncol Vol 8, No 9, 1466-1475, Sept. 1990.
Fisher ER, Park
SM, Rockette H, Jones J, Caplan R, and Fisher B: Prognostic
Significance of Eosinophils and Most Cells in Rectal Cancer: Findings
From the National Surgical Adjuvant Breast and Bowel Project (Protocol
R-01). Hum Path 20: 159-163, 1989.
Fisher B, Wolmark
N, Rockette H, Redmond C, Deutsch M, Wickerham D,
Fisher E, Caplan R, Lerner H, Gordon P, Feldman M, Cruz A, Legault-Poisson
S, and Other NSABP Investigators: Postoperative adjuvant chemotherapy
or radiation therapy for rectal cancer: results from NSABP Protocol
R-01. J Nat Cancer Inst. Vol 80, March 2, :21-29, 1988.
Wolmark N, Fisher
B, Rockette H, Redmond C, Wickerham D, Fisher E,
Jones J, Lerner H, Lawrence W, Prager D, Wexler M, Evans R, and
Other NSABP Investigators: Postoperative adjuvant chemotherapy
or BCG for colon cancer: Results from NSABP Protocol C-01. Journal
of the National Cancer Institute, 80, 30-36, March 2, 1988.
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NSABP - Prevention Trials
In 1992 the National
Surgical Adjuvant Breast and Bowel Project initiated the Breast
Cancer Prevention Trial (BCPT). The specific aim of this large-scale,
randomized clinical trial was to test the hypothesis that long-term
treatment with tamoxifen is effective in preventing invasive breast
cancer. Breast cancer risk profiles were generated for more than
98,000 women of whom more than 57,000 met the eligibility criteria
for the trial. Ultimately, more than 13,000 women at high risk from
breast cancer were randomized to receive either tamoxifen or a placebo.
Faculty in the Biostatistics Department had a major role in the
design, conduct and analysis of this clinical trial. Since participants
at the time of entry into the study are healthy and do not have
disease, there is a need to have a more refined method of risk assessment
than is required in most treatment trials. The results of the trial
indicated almost a 50% reduction in the incidence of invasive breast
cancer in the groups randomized to tamoxifen when compared to the
group randomized to placebo. Not only did the findings from BCPT
provide an additional option for women at high risk from breast
cancer, but it contributed to the improvement of the methodology
related to the assessment and implementation of prevention trials
where there is the potential that risk of treatment may out weigh
the benefit of treatment for some subgroups of patients.
Recently the NSABP
completed accrual of over 19,000 women into the STAR Trial which randomized women at
high risk from breast cancer to receive either tamoxifen or raloxifene as chemotherapy to reduce their risk of developing breast cancer. The goal of this study is to determine if raloxifene will be as effective as tamoxifen in reducing breast cancer risk with the additional benefit of having fewer side effects than tamoxifen. It is anticipated that the final results of this trial will be available by the Spring of 2006. In addition, in mid 2004, the NSABP initiated a trial to evaluate Celebrex as a therapy to prevent colon cancer by reducing the incidence of colon polyps.
Selected Publications:
Wang J, Costantino JP, Tan-Chiu E, Wickerham DL, Paik S, Wolmark N. Lower-category benign breast disease and the risk of invasive breast cancer. J National Cancer Institute, 96:616-629, 2004.
Wickerham DL, Costantino JP. Breast cancer prevention: the U.S.A. viewpoint.
In: Breast Cancer Management: Application of Evidence to Patient
Care, 2nd Ed. Lippincott Williams & Wilkins, Philadelphia,
PA p.535-547, 2003.
Tan-Chiu E, Wang
J, Costantino JP, Paik S, Butch C, Wickerham DL, Wolmark N.
The effect of tamoxifen on benign breast disease in women at high
risk for breast cancer: Findings from the National Surgical Adjuvant
Breast and Bowel Project's Breast Cancer Prevention Trial (BCPT).
J Natl Cancer Inst 95:302-7, 2003.
Vogel VG, Costantino
JP, Wickerham DL, Cronin WM. NSABP update: prevention trials
and endocrine therapy for DCIS. Clin Cancer Res 9:495s-501s,
2003.
Cushman M, Costantino
JP, Bovill EG, Wickerham DL, Buckley L, Roberts JD, Krag DN.
Effect of tamoxifen on venous thrombosis risk factors in women
without cancer: The breast cancer prevention trial. Brit. J.
Haematol 120:109-116, 2003.
Vogel VG, Costantino
JP, Wickerham DL, Cronin WM. Tamoxifen for the prevention
of breast cancer: report of the National Surgical Adjuvant Breast
and Bowel Project P-1Study. J Natl Cancer Inst 94(19):1504,
2002.
Vogel VG, Costantino
JP, Wickerham DL, Cronin WM, and Wolmark N. The study of tamoxifen
and raloxifene: Preliminary enrollment data from a randomized
breast cancer risk reduction trial. Clin Breast Cancer 3(2):153-159,
2002.
Cushman M, Costantino
JP, Tracy RP, Song K, Buckley L, Roberts JD, Krag DN. Tamoxifen
and cardiac risk factors in healthy women: suggestion of an anti-inflammatory
effect. Arterioscler, Thromb and Vasc Biol 2001; 21:255-261.
Costantino,
JP, Vogel VG. Results and Implications of the Royal Marsden
and Other Trials Tamoxifen chemoprevention trials: An Alternative
view. Clinical Breast Cancer 2(1):41-46, 2001.
Costantino,
JP. Benefit/Risk assessment. In: Biostatistics in Clinical
Trials Redmond, C., Colton, T., Ed Wiley, pg. 18-25, 2001
Gail, M.,
Costantino, JP. Validating and improving models for projecting
the absolute risk of breast cancer. J National Cancer Institute
93:334-335, 2001.
Cushman, M.,
Costantino, JP, Tracey R.P., Song, K., Buckey, L., et al.
Tamoxifen and novel cardiac risk factors in healthy women: evidence
for an anti-inflammatory effect. Arterosder Thromb and Vasc
Bio 21:255-261, 2001.
Reis, S.E., Costantino,
JP, Wickerham, D.L., Tan-Chiu, E., Wang, J., et al.
Cardiovascular effects of tamoxifen in women with and without
heart disease. J National Cancer Institute 93:16-21, 2001.
Gail MH, Costantino
JP, Bryant J, Croyle R, Freedman L, Helzlsouer and
Vogel V. Weighing the risks and benefits of tamoxifen for preventing
breast cancer. J Natl Cancer Inst 91:1829-46, 1999.
Costantino
JP, Gail MH, Pee D, Anderson S, Redmond CK,
Benichou J. Validation studies for models to project the risk
of invasive and total breast cancer incidence. J Natl Cancer
Inst 91:1541-48, 1999.
Day R, Ganz PA,
Costantino JP, Cronin WM, Wickerham DL, Fisher B. Health-related
quality of life and tamoxifen in breast cancer prevention: A report
from the National Surgical Adjuvant breast and bowel project P-1
study. J Clin Oncol 17:2659-2669, 1999.
Fisher, B., Costantino,
J., Wickerham, D.L., et al. Tamoxifen for Prevention of Breast
Cancer: Report of the National Adjucant Breast and Bowel Project
Pl Study. Journal National Cancer Inst. 90:1371-1388, 1998.
Ganz, P.A., Day,
R., Costantino, J., Compliance with Quality of Life
Data Collection in the National Surgical Adjuvant Breast and Bowel
Project Breast Cancer Prevention Trial. Statistics In Medicine
17:613-622, 1998.
Fisher B, Costantino
J. Highlights of the NSABP Breast Cancer Prevention Trial.
Cancer Control 4:78-86, 1997.
Redmond CK,
Costantino JP. Design and Current Status of NSABP Breast
Cancer Prevention Trial. Recent Results Cancer Research,
140:309-317, 1996.
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Statistical Methododology
The Department of Biostatistics has been active in the development of new statistical procedures for use in the public health and medical areas. The current faculty has more than one hundred publications in peer reviewed statistical journals. This number does not include the more than fifty additional methodological papers appearing in medical journals and book chapters written to familiarize various disciplines with statistical concepts and procedures. General methodological areas of interest include survival analysis, multivariate methods, sequential methods, missing data analysis, ROC curve analysis and regression diagnostics. Often the methodological research has developed from applied research in which the faculty is participating . This is particularly true in the area of clinical trials and occupational and environmental biostatistics.
Parametric survival models have related mostly to the lognormal (1) and Weibull models (2-5). Considerable work has also been done on more general approaches such as the log rank test (6), the proportional hazards model (7-11), and extensions to multivariate failure time data (12) or nonproportional hazards models (13-14). In some cases methodological work in survival analysis was motivated by the collaborative research in which the faculty participates (15-17).
Developmental work has also been done on sequential methods as they relate both to Phase II (18, 19) and Phase III clinical trials (20-23). Additional related work includes the design of a Phase II trial within a Phase III trial (24), two stage designs for both binary outcomes (25) and survival (26-27). Members of the Department have also been active in the development of methods useful in the design of experiments. These include the previously mentioned sequential methods and two stage designs as well as methods for multiple comparisons (28-30) and sample size estimation (31-32).
The range of interest in methodological problems has varied over time as well as over individual faculty members. Thus, there are publications on more classical areas such as estimation theory (7, 8, 33-36), nonparametric statistics (37-41), multivariate methods (42-65) and linear models (46-48) as well as more recently developed areas such as frailty models (49-50), smoothing splines (51-53), missing data analysis (54-56), semiparametric models (56-57), computer intensive methods (58-60), microarrays (61-62), machine learning (63), copulas (64), and neural networks (65).
Additional areas of activity include regression diagnostics, ROC curve analysis and meta analysis. Regression diagnostics include methods to assess multicollinearity (66, 67, 69) influence diagnostics for various models (2, 10, 68) and residual analysis (70). Several recent papers apply to regression diagnostics for the Cox model (69, 71, 72). ROC curve methodology is being increasingly applied to the evaluation of diagnostic imagining systems and the predictive capability of a statistical model in the clinical setting. There are several papers related to various aspects of these problems (73-78). Meta analysis is a set of procedures and methods which can be used to combine multiple studies. Members of the department have been active in addressing some of the methodological and conceptual issues in meta analysis (79, 80) as well as applying it to a variety of areas of research (81-84).
References
1. Schneider H, and Weissfeld A. Interval Estimation for Accelerated Life Tests Based on the Lognormal Model. Journal of Quality Technology, 21(1):24-31, 1989.
2. Weissfeld LA, and Schneider H. Influence Diagnostics for the Normal Linear Model with Censored Data. Statistics and Probability Letters, 9:67-73, 1990.
3. Schneider H, and Weissfeld LA. Interval Estimation Based on Censored Samples for the Weibull Distribution. Journal of Quality Technology, 21(3):19-186, 1989.
4. Rockette HE, Antle CE, Klimko LA. Maximum likelihood estimation with the Weibull model. J Amer Stat Assn, 1974.
5. Klimko LA, Rockette HE, Antle CE, Rademaker FA. Upper bounds for the power of invariant tests for the exponential distribution with Weibull alternatives. Technometrics, 1975.
6. Jeong J. Efficiency of log-rank test under dependent censorship. Communications in Statistics: Theory and Methods, 32:1197-1211, 2003.
7. Jeong J, and Oakes D. On the asymptotic relative efficiency of estimates from Cox’s model. Sankhya, 65:411-421, 2003.
8. Jeong J, and Oakes D. Effects of different hazards ratios on asymptotic relative efficiency of estimates from Cox’s model. Communications in Statistics - Theory and Methods, in press.
9. Liu K, Mazumdar S, Stone R, Dew MA, Houck PR, and Reynolds CF. Accounting for covariate measurement error in a Cox model and analysis of recurrence depression. Journal of Psychiatric Research, 35:177-185, 2001.
10. Weissfeld LA. Influence Diagnostics for the Proportional Hazards Model. Statistics and Probability Letters, 10:411-417, 1990.
11. Liu K, Stone RA, Mazumdar S, Houck PR, Reynolds CF. Covariate measurement error in the Cox model: a simulation study. Communications in Statistics, in press.
12. Wei LJ, Lin DY, and Weissfeld LA. Regression Analysis of Multivariate Incomplete Failure Time Data by Modeling Marginal Distributions. Journal of the American Statistical Association, 84:1065-1073, 1989.
13. Lee EC, and Weissfeld LA. Assessment of Covariate Effects in Aalen’s Additive Hazard Model. Statistics in Medicine, 17:983-998, 1998.
14. Valenta Z, and Weissfeld LA. Estimation of the Survival Function for Gray’s Piecewise-Constant Time-Varying Coefficients Models. Statistics in Medicine, 21:717-727, 2002.
15. Jeong J, Jung S, Wieand S. A parametric model for long-term follow-up data from phase III breast cancer clinical trials. Statist Med, 22:339-352, 2003.
16. Mazumdar S, Berhane Z, Weissfeld L, Begley A, Dew MA, Houck PR, and Reynolds CF. Survival models with time-varying coefficients: A flexible approach to the analysis of psychiatric survival data. Psychopharmacology Bulletin, 36(4):84-91, 2002.
17. Roberts MS, Angus DC, Bryce CL, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States. A disease-specific analysis of the UNOS database. To appear in Liver Transplantation.
18. Chang MN, Therneau TM, Wieand HS, Cha SS. Designs for group sequential phase II clinical trials. Biometrics, 43:865-874, 1987.
19. Chang MN, Wieand HS, and Chang VT. The bias of the sample proportion following a group sequential phase II clinical trial. Statist in Med, 8:563-570, 1989.
20. Therneau TM, Wieand HS, Chang MN. Optimal designs for a grouped sequential binomial trial. Biometrics, 46:771-781, 1990.
21. Wieand HS, Schroeder G, O’Fallon JR. Stopping when the experimental regimen does not appear to help. Statist in Med, 13:1453-1458, 1994.
22. Dignam J, Bryant J, Wieand S, Fisher B, Wolmark N. Early stopping of a clinical trial when there is evidence of no treatment benefit: Protocol B-14 of the National Surgical Adjuvant Breast and Bowel Project. Controlled Clinical Trials, 19:575-588, 1998.
23. Mor MK, and Anderson S. A Bayesian Group Sequential approach for multiple endpoints. To appear in The Sequential Analysis Journal, 2004.
24. Schaid DJ, Ingle JN, Wieand HS, Ahmann DL. A design for phase II testing of anti-cancer agents within a phase III clinical trial. Controlled Clinical Trials 9:107-118, 1988.
25. Wieand HS, Therneau T. A two-stage design for randomized trials with binary outcomes. Controlled Clinical Trials 8:20-28, 1987.
26. Schaid DJ, Wieand HS, Therneau TM. Optimal two-stage screening designs for survival comparisons. Biometrika, 77:507-513, 1990.
27. Wahed A and Tsiatis AA. Optimal estimator for the survival distribution and related quantities for treatment policies in two-stage randomization designs in clinical trials. Biometrics, Vol. 60, No. 1, pp 124-133, 2004.
28. Bryant J, Fox G. Some Comments on a Class of Simultaneous Inference Procedures in ANCOVA. Communications in Statistics, 14:2511-2530, 1985.
29. Bryant J, Bruvold N. Multiple Comparison Procedures in the Analysis of Covariance. Journal of the American Statistical Association, 75:874-880, 1980.
30. Bryant J, Paulson A. An Extension of Tukey’s Method of Multiple Comparisons to Experimental Designs with Random Concomitant Variables. Biometrika, 63:631-638, 1976.
31. Ahnn S, and Anderson SJ. Sample size determination in complex clinical trials comparing more than two groups for survival endpoints. Statistics in Medicine, 17:2525-2534, 1998.
32. Ahnn S, and Anderson SJ. Sample size calculations for comparing k survival distributions. Statistics in Medicine, 14:2273-2282, 1995.
33. Sinha BK, Wieand HS. Admissibility and minimaxity of a MVUE when the parameter space is restricted to integers. Calcutta Statist Assoc Bulletin, 25:165-168, 1975.
34. Wieand HS. On a condition under which the Pitman and Bahadur approaches to efficiency coincide. Ann Statist, 4:1003-1011, 1976.
35. Sinha BK, Wieand HS. Admissibility and inadmissability of the MLE when the parameter space is restricted to integers. Calcutta Statist Assoc Bulletin, 26:113-116, 1977.
36. Ghosh JK, Sinha BK, Wieand HS. Second order efficiency of the MLE with respect to any bounded, bowl-shaped loss function. Ann Statist, 8:506-521, 1980.
37. Sinha BK, Wieand HS. Multivariate nonparametric tests for independence. J Multi Anal, 7:572-583, 1977.
38. Sinha BK, Wieand HS. Bounds on the efficiencies of four commonly used nonparametric tests of location. Sankhya, Ser B, 39:121-129, 1977.
39. Bush JR, Wieand HS. An asymptomatically optimal nonparametric statistic optimal for testing equality of two normal population means and variables. Communications in Statist A, 11:1-12, 1982.
40. Weissfeld L, Wieand HS. Bounds on the efficiencies of some commonly used nonparametric tests. Communications in Statist A, 13:1741-1758, 1984.
41. Wieand HS, Gail MH, James B, James K. Nonparametric procedures for comparing diagnostic tests with paired or unpaired data. Biometrika, 76:585-592, 1989.
42. Miller B, Mazumdar S. Estimation of parameters of a polynomial model under intra class correlation structure for incomplete longitudinal data. Communications in Statistics, Theory and Methods, 15(5):1549-1559, 1986. [Errata (1987), 16, 1541].
43. Sinha BK, Wieand HS. Union-intersection test fo the mean vector when the covariance matrix is totally reducible. J Am Statist Assoc, 74:340-343, 1977.
44. Tate RL, Bryant JL. Parameter Sensitivity for Discriminant Analysis. Multivariate Behavioral Research, 21:411-427, 1986.
45. Tian W, and Anderson SJ. Markov chain models fo multivariate repeated binary data analysis. Communications in Statistics, Simulation and Computation, 29(4), 2000.
46. Schneider H, and Weissfeld LA. Estimation in Linear Models with Censored Data. Biometrika, 73:741-745, 1986.
47. Weissfeld LA, and Schneider H. Inferences Based on the Buckley-James Procedure. Communications in Statistics - Theory Methods, 16(6):1773-1788, 1987.
48. Mazumdar S, Li CC, Bryce GR. Correspondence between a Linear Restriction and a Generalized Inverse in Linear Model Analysis. American Statistician, 34(2):103-105, 1980.
49. Day R, Bryant J, Lefkopoulou M. Adapting Bivariate Frailty Models for Prediction with Application to Biological Markers as Prognostic Indicators. Biometrika, 84:45-56, 1997.
50. Oakes D, and Jeong J. Frailty models and rank tests. Lifetime Data Analysis, 4:209-228, 1998.
51. Berhane K, and Weissfeld LA. Inference in spline based models fo the multiple time-to-event data: with applications to a breast cancer prevention trial. To appear in Biometrics, 2003.
52. Anderson SJ, and Jones RH. Smoothing splines for longitudinal data. Statistics in Medicine, 14:1235-1248, 1995.
53. Anderson SJ, Jones RH, and Swanson GD. Smoothing polynomial splines for bivariate data. SIAM Journal of Scientific and Statistical Computing, 11(4), 1990.
54. Tang G, Little RJA, and Raghunathan TE. Analysis of Multivariate Missing Data with Nonignorable Nonresponse. Biometrika, 90(4):747-764, 2003.
55. Mazumdar S, Liu K, Houck PR, and Reynolds CF. Intent-to-treat analysis for longitudinal clinical trials: coping with the challenge of missing values. Journal of Psychiatric Research, 33:87-95, 1999.
56. Zhang Z, Rockette HE. On maximum likelihood estimation in parametric regression with missing covariates. Journal of Statistical Planning and Inference, (in press) 2004.
57. Kong L, Jianwen C and Sen PK. Weighted estimating equations for semiparametric transformation models with censored data from a case-cohort design. Biometrika, 2004, in press.
58. Sussman NB, Arena VC, Yu S, Mazumdar S, Thampatty BP. Decision tree SAR models for developmental toxicity based on an FDA/TERIS database. SAR and QSAR in Environmental Research, 14(2):83-96, 2003.
59. Arena VC, Sussman NB, Mazumdar S, Yu S, Macina OT. The utility of structure-activity relationship (SAR) models for prediction and covariate selection in developmental toxicity: comparative analysis of logistic regression and decision tree models. SAR and QSAR in Environmental Research, 15(1):1-18, 2004.
60. Tseng GC, and Wong WH. Tight Clustering: A Resampling-based Approach for Identifying Stable and Tight Patterns in Data. Biometrics, 2004 (in press).
61. Tseng GC, Oh M-K, Rohlin L, Liao JC, and Wong WH. Issues in cDNA microarray analysis : quality filtering, channel normalization, modes of variations and assessment of gene effects. Nucleic Acids Research, 29:2549-2557, 2001.
62. Hwang J-J, Allen PD, Tseng GC, Lam C-W, Fananapazir L, Dzau VJ, and Liew C-C. Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiological Genomics, 10:31-44, 2002.
63. Shen X, Tseng GC, Zhang X, and Wong WH. On psi-Learning. Journal of American Statistical Association, 98:724-734, 2003.
64. Phelps A, and Weissfeld LA. AA Comparison of Dependence Estimators in Bivariate Copula Models. Communications in Statistics - Simulation and Computation, 26(4): 1583-1598, 1997.
65. Landsittel D, Singh H, Arena VC and Anderson SJ. Null distribution of the likelihood ratio statistic for feed-forward neural networks. The Journal of Modern Applied Statistical Methods, 1(2):333-342, 2002.
66. Weissfeld LA. A Multicollinearity Diagnostic for Models Fit to Censored Data. American Statistical Association, 18:2073-2085, 1989.
67. Weissfeld LA, and Sereika S. A Multicollinearity Diagnostic for Discrete Response Models. Communications in Statistics, 20(4):1183-1198, 1991.
68. Weissfeld LA, and Schneider H. Influence Diagnostics for the Normal Linear Model with Censored Data. Australian Journal of Statistics, 32:11-20, 1990.
69. Lee KY, and Weissfeld LA. A Collinearity Diagnostic for the Cox Proportional Hazards Model with Time Dependent Covariate. Communications in Statistics - Simulation and Computation, 25(1): 41-59, 1996.
70. Weissfeld LA, and Schneider H. Residual Analysis for Parametric Models Fit to Censored Data. Communications in Statistics - Theory and Methods, 23(8):2283-2298, 1994.
71. Jung S, Wieand HS. Analysis of goodness-of-fit test for Cox regression model. Statistics and Probability Letters, 41:379-382, 1999.
72. Chang CC, and Weissfeld LA. Normal Approximation Diagnostics for the Cox Model. Biometrics, 55(4):1114-1119, 1999.
73. Beam CA and Wieand HS. A statistical method for the comparison of a discrete diagnostic test with several continuous diagnostic tests. Biometrics, 47:907-919, 1991.
74. Jung SH, Wieand HS, Cha SS. A statistic for comparing two correlated markers which are prognostic for time to an event. Statist in Med, 14:2217-2225, 1995.
75. Emir B, Wieand S, Su J, Cha S. Analysis of Repeated Markers Used to Predict Progression of Cancer. Statist in Med, 17:2563-2578, 1998.
76. Emir B, Wieand S, Jung S, Ying Z. Comparison of diagnostic markers with repeated measurements: a non-parametric approach. Statist in Med, 19:511-523, 2000.
77. Obuchowski NA, Rockette HE. Hypothesis testing of diagnostic accuracy for multiple readers and multiple tests: An ANOVA approach with dependent observations. Commun Statistics, 24(2):285-308, 1995.
78. Rockette HE, Li W, Brown ML, Britton CA, Towers JT, Gur D. A statistical test to assess rank order ROC imaging studies. Academic Radiology, 8(1):24-30, 2001.
79. Sankey SS, Weissfeld LA, Fine MJ, Kapoor WN. An Assessment of the Continuity Correction for Sparse Data in Meta-Analysis. Communications in Statistics - Simulation and Computation, 25(4): 1031-1056, 1996.
80. Rockette HE, Redmond CK. Issues related to combining data from multiple randomized clinical trials. Presented at “Medical Statistics: Design and Analysis of Clinical Trials”, Institute of Mathematics, Oberwolfach, Germany, February 1987. Published in Recent Results Cancer Research, 99-104, 1988.
81. Miles PG, Vig PS, Weyant RJ, Forrest TD, and Rockette HE. Craniofacial structure and obstructive sleep apnea syndrome - a qualitative analysis and meta-analysis of the literature. Orthod Dentofac Orthop, 109:163-172, 1996.
82. Rockette HE, Gur D, Campbell WL, Thaete FL. Utilization of meta analysis in the evaluation of imaging systems. Academic Radiology, 1:63-69, 1994.
83. Fine MJ, Smith MA, Carson CA, Meffe F, Sankey SS, Weissfeld LA, Detsky AS, Kapoor WN. Efficacy of Pneumococcal Vaccination in Adults: A Meta-Analysis of Randomized Controlled Trials. Archives of Internal Medicine, 154(23):2666-2677, 1994.
84. Nowell PD, Mazumdar S, Buysse DJ, Dew MA, Reynolds CF, and Kupfer DJ. Benzodiazepines and Zolpidem for Chronic Insomnia: A Meta-Analysis of Treatment Efficacy. Journal of the American Medical Association, 278(24):2170-2177, 1997.
85. Starr TB, Gause CK, Youk AO, Stone RA, Marsh GM, Collins JJ. A risk assessment for occupational acrylonitrile exposure using epidemiology data. Risk Analysis 2004;24:587-601.
86. Youk AO, Stone RA, Marsh GM. A method for imputing missing data in longitudinal studies. Annals of Epidemiology 2004;14:354-361.
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Health Outcomes/Health Services Research
Health outcomes/health services research is a pragmatic, multidisciplinary approach for assessing clinical decision making, access to care, cost containment, resource allocation, quality of care, and patient-centered medical outcomes and patient satisfaction. Health services research also includes observational studies to document the role of patient, provider and site characteristics in delivery of medical care, as well as intervention studies to improve the performance of recommended processes of care. The department currently conducts health services research in diverse settings including the Veteran's Administration (VA) Healthcare System, the UPMC Healthcare System, local health insurance providers, pediatric trauma centers and the manufacturing industry. At the Center for Health Equity Research and Promotion at the Pittsburgh VA , multiple studies are planned or ongoing to improve care for vulnerable populations of veterans. In collaboration with the UPMC Healthcare System and other sites, the Pneumonia Patient Outcomes Research Team study documented current practices and developed a medical practice guideline for patients with community acquired pneumonia (CAP). A series of subsequent studies evaluated interventions to improve the delivery of care, including the admission decision, choice and duration of antibiotics, length of stay, and the discharge decision. The department has been involved in the identification of under- and over-users of health resources in a managed care setting, reliability studies on medical record abstraction, survey methods to characterize health care providers, and assessment of patient satisfaction. Research areas include pediatric trauma and registry development. Identification and evaluation of risk factors and treatment of pediatric trauma; such as developing pediatric trauma scoring systems for survival and disability. Registry development projects include a designing a national trauma registry for children (NTRC) and a project to develop, maintain and analyze an occupational medical claims registry.
Selected Publications:
Aujesky DA, Stone RA, Obrosky DS, Yealy DM, Auble TE, Meehan TP, Graff LG, Fine JM, Fine MJ. How good is the agreement between retrospectively and prospectively collected data comprising the pneumonia severity index? Journal of Clinical Epidemiology (to appear).
Aujesky DA, Auble TE, Yealy DM, Obrosky DS, Stone RA, Fine MJ. Prospective comparison of three validated prediction rules for prognosis in community-acquired pneumonia. Am J Med (to appear).
Yealy DM, Auble TE, Stone RA, Lave JR, Meehan TP, Graff LG, Fine JM, Obrosky DS, Edick SM, Hough LJ, Tuozzo K, Fine MJ. The emergency department community-acquired pneumonia trial: methodology of a quality improvement intervention. Annals of Emergency Medicine 2004; 43(6):1-13.
Fine MJ, Stone RA, Lave JR, Hough LJ, Obrosky DS, Mor MK, Kapoor WN. Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia. American Journal of Medicine 2003; 115:343-351.
Cassidy LD, Marsh GM, Holleran MK, Ruhl LS. Methodology to improve data quality from chart review in the managed care setting. American Journal of Managed Care 2002; 8:787-793.
Lear D, Schall LC, Marsh GM, Liu KS , Yao Y. Identification and case management in an HMO of patients at risk of preterm labor. American Journal of Managed Care 1998; 4:865-871.
Fine MJ, Stone RA, Singer DE, Coley CM, Marrie TJ, Lave JR, Hough LJ, Obrosky DS, Schulz R, Ricci EM, Rogers JC, Kapoor WN. Processes and outcomes of care for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study. Archives of Internal Medicine 1999; 159: 970-980.
Gleason PP, Kapoor WN, Stone RA, Lave JR, Obrosky DS, Schulz R, Singer DE, Coley CM, Marrie TJ, Fine MJ. Medical outcomes and antimicrobial costs with the use of the American Thoracic Society guidelines for outpatients with community-acquired pneumonia. JAMA 1997; 278:32-39.
Fine MJ, Medsger AR, Stone RA, Marrie TJ, Coley CM, Singer DE, Akkad H, Hough LJ, Lang W, Ricci EM, Polenik DM, Kapoor WN. The hospital discharge decision for patients with community-acquired pneumonia. Results from the Pneumonia Patient Outcomes Research Team cohort study. Archives of Internal Medicine 1997; 157:47-56.
Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN . A prediction rule to identify low-risk patients with community-acquired pneumonia. New England Journal of Medicine 1997;336:243-250
Fine MJ, Hanusa BH, Lave JR, Singer DE, Stone RA, Weissfeld LA, Coley CM, Marrie TJ, Kapoor WN. Comparison of a disease-specific and a generic severity of illness measure for patients with community-acquired pneumonia. Journal of General Internal Medicine 1995; 10:359-368.
Stone RA, Obrosky DS, Singer DE, Kapoor WN, Fine MJ. Propensity score adjustment for pretreatment differences between hospitalized and ambulatory patients with community-acquired pneumonia. Pneumonia Patient Outcomes Research Team (PORT) Investigators. Medical Care 1995; 33(4 Suppl):AS56-66.
Cassidy LD, Potoka DA, Ford HR. “ Development of a Novel Method to Predict Disability Following Head Trauma in Children.” J Ped Surgery. 38(3): 482-485, Mar 2003.
Schall LC, Potoka DA, Ford HR. Journal of Trauma . 52(2):235-41, Feb 2001. “A New Method for Estimating Probability of Survival in Pediatric Patients Using Revised TRISS Methodology Based on Age-Adjusted Weights”.
Potoka DA, Schall LC, Ford HR. "Development of a Novel Age-Specific Pediatric Trauma Score." Journal of Pediatric Surgery . 2000; 36(1):106-112.
Potoka DA, Schall LC, Gardner M, Stafford P, Peitzman AB , Ford HR."Impact of Pediatric Trauma Centers on Mortality in a Statewide System." Journal of Trauma. August 2000.
Potoka DA, Schall LC, Ford HR. “Risk factors for splenectomy in children with blunt splenic trauma”. J. Ped Surgery. 37(3):294-9, Mar 2002.
Potoka DA, Schall LC, Ford HR et al. “Improved Functional Outcome and Decreased Length of Stay for Severely Injured Children Treated at Pediatric Trauma Centers.” Journal of Trauma . 51(5):824-32, Nov 2001
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Statistical Genetic Research
The Department has a long history of research in statistical genetics in
collaboration with the Division of Statistical Genetics in the Department of
Human Genetics. Focuses include linkage analysis for mapping susceptibility
genes in complex diseases (1, 2, 3) and methods for mapping genes for quantitative traits using selected sibships (4, 5). Another recent focus has
moved to the rapidly evolving field of bioinformatics. It includes
statistical modelling and hypothesis esting for differentially expressed
genes (6, 7), gene-gene interaction (8), cluster analysis (9, 10) and
machine learning (11) in large scale genomic or proteomic data such as those
from microarray, serial analysis of gene expression (SAGE) and mass
spectrometry (12) experiments.
Related research also includes exploring a mechanism to find gene markers
that are associated with survival outcome and applying those in cancer
clinical trials (13).
1. Mukhopadhyay N, Finegold DN, Larson MG, Cupples LA, Myers RH, Weeks DE (2003) A genome-wide scan for loci affecting normal adult height in the
Framingham Heart Study. Hum Hered 55:191-201.
2. Weeks DE, Conley YP, Tsai HJ, Mah TS, Schmidt S, Postel EA, Agarwal A,
Haines JL, Pericak-Vance MA, Rosenfeld PJ, Paul TO, Eller AW, Morse LS,
Dailey JP, Ferrell RE, Gorin MB (2004) Age-related maculopathy: A genomewide
scan with continued evidence of susceptibility loci within the 1q31, 10q26,
and 17q25 regions. Am J Hum Genet 75:174-189.
3. Zondervan KT, Weeks DE, Colman R, Cardon LR, Hadfield R, Schleffler J,
Trainor AG, Coe CL, Kemnitz JW, Kennedy SH (2004) Familial aggregation of
endometriosis in a large pedigree of rhesus macaques. Hum Reprod 19:448-455.
4. Szatkiewicz JP, Feingold E. A powerful and robust new linkage statistic
for discordant sibling pairs. American Journal of Human Genetics,
75:906-909, 2004.
5. Szatkiewicz JP, Feingold E. QTL mapping with discordant and concordant
sibling pairs - new statistics and new design strategies. Genetic
Epidemiology, in press.
6. George C. Tseng, Min-Kyu Oh, Lars Rohlin, James C. Liao, and Wing Hung
Wong. (2001) Issues in cDNA microarray analysis: quality filtering, channel
normalization, models of variations and assessment of gene effects. Nucleic
Acids Research. 29: 2549-2557.
7. Lin Y, Reynolds P, Feingold E. An Empirical Bayesian Method for
Differential Expression Studies Using One-Channel Microarray Data.
Statistical Applications in Genetics and Molecular Biology, 2(1):Article 8,
2003.
8. "Weakest Link Models for Detecting Small Groups of Genes to Predict Lung
Cancer Survival, CAMDA'03 (Critical Assessment of Microarray Data Analysis",
Richards TJ, Day RS, Kaminski N. Durham, North Carolina, November 2003.
9. George C. Tseng. (2004) A Comparative Review of Gene Clustering in
Expression Profile. 8th International Conference on Control, Automation,
Robotics and Vision (ICARCV). 1320-1324.
10. George C. Tseng and Wing H. Wong. (2005) Tight Clustering: A
Resampling-based Approach for Identifying Stable and Tight Patterns in Data.
Biometrics. 61:10-16.
11. Xiaotong Shen, George C. Tseng, Xuegong Zhang, and Wing H. Wong. (2003)
On psi-Learning. Journal of American Statistical Association. 98:724-734.
12. Yingying Huang, Joseph M. Triscari, George C. Tseng, Ljiljana
Pasa-Tolic, Mary S. Lipton, Richard D. Smith, Vicki H. Wysocki. (2005)
Statistical Characterization of Charge State and Residue Dependence of Low
Energy CID Peptide Dissociation Patterns. (submitted to Analytical
Chemistry).
13. Soonmyung Paik, Steven Shak, Gong Tang, Chungyeul Kim, Joffre Baker,
Maureen Cronin, Frederick L. Baehner, Michael G. Walker, Drew Watson,
Taesung Park, William Hiller, Edwin R. Fisher, D. Lawrence Wickerham, John
Bryant, and Norman Wolmark. New England Journal of Medicine 2004;
351:2817-26.
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Occupational & Environmental Epidemiology
The Department
of Biostatistics has a long history of conducting studies that investigate
the relationship of occupational exposure to elevated risks of cancer.
Often such studies entailed the formation of industry-wide cohort
studies of occupational groups with the exposures of interest. The
Department has conducted more than two dozen occupational cohort
studies totaling more than 250,000 workers. Occupational studies
conducted include asbestos workers, coal miners, steel workers,
aluminum reduction plant workers, chemical workers, man-made vitreous
fiber (fiber glass and rock/slag wool) workers, nickel workers,
workers in copper smelting and pharmaceutical workers. Faculty members
also direct a bladder cancer screening program for workers at high
risk of bladder cancer from prior occupational exposure to the potent
carcinogen, beta-naphthylamine (BNA).
Previous studies
conducted by faculty in the Department of Biostatistics (1) were
among the first to demonstrate the relationship of lung cancer to
asbestos exposure; (2) characterized the mortality patterns of coal
miners; (3) provided the scientific information necessary to set
standards for coke oven emissions; (4) characterized the mortality
patterns for a wide range of jobs within the steel industry; (5)
better delineated the relationship of lung cancer to exposure from
arsenic; and (6) characterized the exposure-response relationships
for respirable man-made vitreous fibers and malignant and non-malignant
respiratory disease, formaldehyde and nasopharyngeal and lung cancer,
and acrylonitrile and lung and brain cancer. Often the early studies
conducted by the Department in these areas led to improvement in
the methods used to conduct, quality control and analyze this type
of epidemiological study. Faculty have also been involved in the
re-analysis of large scale occupational cohort studies conducted
by the National Cancer Institute (NCI) and the National Institute
for Occupational Safety and Health (NIOSH).
In addition, Department
faculty members have developed software programs and data base systems
to facilitate the conduct of these studies. Examples of these tools,
the Occupational Cohort Mortality Analysis
Program (OCMAP) and the Mortality and Population
Data System (MPDS) are described in other sections.
Relating general
environmental exposures to excess risk is more difficult than risk
assessment in an occupational group since exposures in the general
environment are more difficult to characterize. Studies done by
faculty in the Department of Biostatistics in the area of environmental
epidemiology have related to estimating the effects of air pollution
on mortality, identifying cancer risks in communities surrounding
industrial plants, development of models to assess reproductive
risks in animal studies, and assessment of the excess risk of cardiovascular
disease resulting from smoking and alcohol usage. Examples of environmental
studies include health effects investigations of communities with
potential environmental exposures due to residing near point sources
of pollution. These sources include, Arizona copper smelters, chemical
plants in the Kanawha River valley of WV, and U.S. Environmental
Protection Agency (EPA) PA Superfund sites, such as a PA chemical
plant that used BNA.
Faculty in the Biostatistics Department collaborated with the faculty members in the Department of Environmental and Occupational Health in the area of computational toxicology, one of the research areas of the EOH Department. This effort has been mostly in addressing methodological issues, developing methods and related software.
Stone RA, Youk AO, Marsh GM, Buchanich JM, Smith TJ. Historical cohort study of U.S. Man-made vitreous fiber production workers IX: summary of 1992 mortality follow up and analysis of respiratory system cancer among female workers. J Occup Environ Med 2004;46:55-67.
Wei L, Mazumdar S, Arena VC and Sussman N. A resampling approach for adjustment in prediction models for covariate measurement error. Computer Methods and Programs in Biomedicine (in press).
Arena VC, Sussman NB, Mazumdar S, Yu S, Macina OT. The utility of structure-activity relationship (SAR) models for prediction and covariate selection in developmental toxicity: comparative analysis of logistic regression and decision tree models. SAR and QSAR in Environmental Research, 15(1), 1-18, 2004.
Li W, Arena VC, Sussman NB, and Mazumdar S. Model validation software for classification models using repeated partitioning:MVREP. Computer Methods and Programs in Biomedicine, 72 (2003) 81-87.
Sussman NB, Arena VC, S. Yu , Mazumdar S, Thampatty BP. Decision tree SAR models for developmental toxicity based on an FDA/TERIS database . SAR and QSAR in Environmental Research, 2003, 14(2), 83-96.
Marsh GM,
Gula MJ, Roggli V, Churg A. The Role of Smoking and Asbestos Exposure
in a Questionable Case of Mesothelioma. Industrial Health,
2003 (In Press).
Cassidy LD,
Youk AO, Marsh GM. The Drake Health Registry Study:
Cause-Specific Mortality among Workers with Probable Past Exposure
to Beta-naphthylamine. American Journal of Industrial Medicine,
2003 (In Press)
Bloemen LJ, Youk
AO, Bradley TD, Bodner KM, Marsh GM, Collins JJ. Lymphohematopietic
Cancer among Chemical Workers Exposed to Benzene. Occupational
and Environmental Medicine, 2003 (In Press).
Marsh GM,
Cassidy LD. The Drake Health Registry Study: Findings from
Fifteen Years of Continuous Bladder Cancer Screening. American
Journal of Industrial Medicine, 43:142-148, 2003.
Talbott EO, YOUK
AO, Pemu-McHugh K, Zoborowski J. Long Term Follow-Up of the
Residents of the Three Mile Island Area: 1979-1998. Environmental
Health Perspectives, 11(3):341-348, 2003.
Schall LC,
Marsh GM, Holleran MK, Ruhl LS. Methodology to Improve
Data Quality from Chart Review in the Managed Care Setting. American
Journal of Managed Care, 8:787-793, 2002.
Marsh GM, Youk AO, Stone RA, Buchanich JM,
Gula MJ, Smith TJ, Churg A, Colby T. Does Fiber Glass Pose a Respiratory
Cancer Risk in Man? Findings from the Latest Update of the U.S.
Cohort Study of Man-Made Vitreous Fiber Workers. Annals of
Occupational Hygiene, 46(Supp.1): 110-114, 2002.
Marsh GM, Gula MJ, Youk AO, Cassidy LD. Bladder
Cancer among Chemical Workers Exposed to Nitrogen Products and
Other Substances. American Journal of Industrial Medicine,
42:286-295, 2002.
Marsh GM,
Youk AO, Stone, RA, Buchanich JM, Gula MJ, Smith
TJ, Quinn MM: Historical Cohort Study of U.S. Man-Made Vitreous
Fiber Production Workers. I. 1992 Fiber Glass Cohort Follow-Up-
Initial Findings. Journal of Occupational and Environmental
Medicine 43:741-756, 2001.
Marsh GM,
Youk AO, Collins J: A Reevaluation of Lung Cancer Risk
in the NCI/NIOSH Acrylonitrile Cohort Study. Scandinavian Journal
of Work, Environment and Health 27:5-13, 2001.
Schall LC,
Buchanich, JM, Marsh GM, Bittner G: Utilizing Multiple
Vital Status Tracing Services Optimizes Mortality Follow-Up in
Large Cohort Studies. Annals of Epidemiology 11:292-296,
2001.
Marsh GM,
Gula MJ, Youk AO, Buchanich JM, Churg A, Colby TV: Historical
Cohort Study of U.S. Man-Made Vitreous Fiber Production Workers.
II. Mortality from Mesothelioma. Journal of Occupational and
Environmental Medicine 43:757-766, 2001.
Youk AO,
Marsh GM, Stone RA, Buchanich JM, Smith TJ: Historical
Cohort Study of U.S. Man-Made Vitreous Fiber Production Workers.
III. Analysis of Exposure-Weighted Measures of Respirable Fibers
and Formaldehyde in the Nested Case-Control Study of Respiratory
System Cancer. Journal of Occupational and Environmental Medicine
43:767-778, 2001.
Stone RA,
Youk AO, Marsh GM, Buchanich JM, McHenry MB, Smith
TJ: Historical Cohort Study of U.S. Man-Made Vitreous Fiber Production
Workers. IV. Quantitative Exposure-Response Analysis of the Nested
Case-Control Study of Respiratory System Cancer. Journal of
Occupational and Environmental Medicine 43:779-792, 2001.
Buchanich JM,
Marsh GM, Youk AO: Historical Cohort Study of U.S.
Man-Made Vitreous Fiber Production Workers. V. Tobacco Smoking
Habits. Journal of Occupational and Environmental Medicine
43:793-802, 2001.
Marsh GM,
Buchanich JM, Youk AO: Historical Cohort Study of U.S.
Man-Made Vitreous Fiber Production Workers. VI.Respiratory System
Cancer SMRs Adjusted for the Confounding Effect of Cigarette Smoking.
Journal of Occupational and Environmental Medicine 43:803-808,
2001.
Smith TJ, Quinn
MM, Marsh GM, Youk AO, Stone RA, Buchanich
JM, Gula MJ: Historical Cohort Study of U.S. Man-Made Vitreous
Fiber Production Workers. VII. Overview of the Exposure Assessment.
Journal of Occupational and Environmental Medicine 43:809-823,
2001.
Quinn MM, Smith
TJ, Youk AO, Marsh GM, Stone, RA, Buchanich
JM, Gula MJ: Historical Cohort Study of U.S. Man-Made Vitreous
Fiber Glass Production Workers VIII. Exposure-Specific Job Analysis.
Journal of Occupational and Environmental Medicine 43:824-834,
2001.
Mazumdar S,
XU Y, Mattison DR, Sussman NB, and Arena VC. Statistical
Methods For Reproductive Risk assessment. Hand Book of Statistics,
Vol. 18. Bio-environmental and Public Heath Statistics. Editors:
P. K. Sen and C.R. Rao. 2000 Elsiever Science, PP 649-671.
Arena VC,
Costantino JP, Sussman NB, Redmond CK: Issues and
Findings in the Evaluation of Occupational Risk in Women: The
High Nickel Alloys Cohort. American Journal of Industrial Medicine,
36, 114-121, 1999.
Marsh GM,
Gula MJ, Youk AO, Schall LC: Mortality Among Chemical
Plant Workers Exposed to Acrylonitrile and Other Substances. American
Journal of Industrial Medicine, 36, 423-436, 1999.
Marsh GM,
Lucas L, Youk AO, Schall LC: Mortality Patterns
Among Workers Exposed to Acrylamide: 1994 Follow-Up. Occupational
and Environmental Medicine, 56, 181-190, 1999.
Esmen NA, Hall
TA, Stone RA, Marsh GM, Gula MJ, Gause CK: An Investigation
of Secondary Exposure Misclassification Effects of Lifelong Occupational
History in Exposure Estimation. American Industrial Hygiene
Association Journal, 60, 175-181, 1999.
Mazumdar S,
Xu Y, Mattison DR, Sussman N, and Arena VC. Reproductive
Risk Assessment with Longitudinal data. The Journal of Applied
Statistical Sciences IV 59-75, 1999.
Mattison DR,
Mazumdar S, XU Y, Sussman N, and Arena VC. Characterizing
reproductive risks using biological markers of reproductive toxicity:
In Biomarkers: Medical and Workplace Applications. Editors: Mendelsohn
ML, Mohr LC and Peeters JP. Joseph Henry Press: A publication
of the National Academy of Sciences. Washington D.C. Pages 323-33,
1998.
Arena VC,
Sussman NB, Redmond CK, Costantino JP, Trauth JM:
Using Alternative Comparison Populations to Assess Occupational
Related Mortality Risk: Results for High Nickel Alloys Workers
Cohort. Journal of Occupational and Environmental Medicine,
40, 907-916, 1998.
Marsh GM,
Youk AO, Stone RA, Sefcik S, Alcorn C: OCMAP-PLUS,
A New Program for the Comprehensive Analysis of Occupational Cohort
Data. Journal of Occupational and Environmental Health,
40, 351-362, 1998.
Rockette HE:
Occupational Biostatistics. Chapter 6 in Environmental and Occupational
Medicine, Little, Brown and Company, Boston MA (William N. Rom
ed) 3rd edition, 1998.
Marsh GM,
Stone RA, Esmen NA, Gula MJ, Gause CK, Petersen NJ, Meaney
FJ, Rodney S, Prybylski D. A Case-Control Study of Lung Cancer
Mortality in Four Rural Arizona Smelter Towns. Archives of
Environmental Health 1998; 53:15-28.
Marsh GM,
Stone RA, Esmen NA, Gula MJ, Gause CK, Petersen NJ, Meaney
FJ, Rodney S, Prybylski D. A Case-Control Study of Lung Cancer
Mortality in Six Gila Basin, Arizona Smelter Towns. Environmental
Research 1997; 75:56-72.
Mazumdar SM,
Mattison DR and Damaraju CV: Temporal issues in reproductive risk
assessment. Inhalation Toxicology, 7, 837-862, 1995.
Mazumdar S,
Mattison DR and Damaraju CV. Issues and Approaches for assessing
risks from reproductive toxicants: DBCP as a case study. SANKHYA,
57, series B, Pt. 2, 223-236, 1995.
Gitelman JH,
Alderman FR, Kurs Lasky M, Rockette HE: Serum and urinary
aluminum levels of workers in the aluminum industry. Ann Occup
Hyg Vol 39, No 2, PP 181-191, 1995.
Marsh GM,
Stone RA, Esmen NA, Henderson VL: Mortality Among Chemical
Plant Workers Exposed to Formaldehyde and Other Substances. Journal
of the National Cancer Institute, 86, 384-385, 1994.
Redmond CK,
Mazumdar S: Design, Analysis and Interpretation of Long-term
Mortality Studies of Coke Oven Workers. International Statistical
Review, 61, 2, 207-221, 1993.
Rockette HE:
What evidence is needed to link lung cancer and second-hand smoke?
Chance 1993, Vol. 6, No. 4: 15-18.
Marsh GM,
Stone RA, Henderson V: Lung Cancer Mortality among Industrial
Workers Exposed to Formaldehyde: A Poison Regression Analysis
of the National Cancer Institute Study. American Industrial
Hygiene Association Journal, 53, 681-691, 1992.
Zhou SYJ, Mazumdar
S, Redmond CK, Dong MH, Costantino JP: Computations
of Adjusted Rates and Lifetime Risks from Occupational Cohort
Data: A Program Package using FORTRAN and GLIM. Computers and
Biomedical Research, 24, 29-46, 1991.
Mazumdar S,
Redmond CK, Costantino JP, Patwardhan RN, Zhou SYJ:
Recent Developments in the Multistage Modeling of Cohort Data
for Carcinogenic Risk Assessment. Environmental Health Perspective,
90, 271-277, 1991.
Marsh GM,
Leviton LC, Talbott E, Callahan C, Pavlock D, Hemstreet G, Logue
JN, Fox J, Schulte, P: The Drake Chemical Workers Health Registry
Study: I. Notification and Medical Surveillance of a Group of
Workers at High Risk of Developing Bladder Cancer. American
Journal of Industrial Medicine, 19, 291-302, 1991.
Marsh GM,
Enterline PE, Stone RA, Henderson VL: Mortality
Among a Cohort of US Man-made Mineral Fiber Workers: 1985 Follow-upJournal
of Occupational Medicine, 32, 594-604, 1990.
Rao BR, Marsh
GM: Simultaneous Statistical Inference Concerning the SMR's
of Several Strata in an Epidemiologic Study. Biometrical Journal,
32, 107-123, 1990.
Mazumdar S,
Redmond CK, Enterline PE, Marsh GM, Costantino
JP, Zhou SYJ, Patwardhan RN: Multistage Modeling of Lung Cancer
Mortality Among Arsenic Exposed Copper-Smelter Workers. Risk
Analysis, 9, 551-563, 1989.
Rao BR, Marsh
GM, Winwood J: Asymptotic Interval Estimation of Some Cause-Specific
Mortality Risk Measures in Epidemiologic Studies. Biometrical
Journal, 31, 461-475, 1989.
Marsh GM,
Co-Chien H, Rao BR, Ehland J: OCMAP: Module 6 - A New Computing
Algorithm for Proportional Mortality Analysis. American Statistician,
43, 127-128, 1989.
Dong MH, Redmond
CK, Mazumdar S, Costantino JP: A Multistage
Approach to the Cohort Analysis of Lifetime Lung Cancer Risk Among
Steelworkers Exposed to Coke Oven Emissions. American Journal
of Epidemiology, 128, 4, 860-873, 1988.
Marsh GM,
Costantino JP, Lyons EE, Logue JN, Fox JM: Health Effects
of Exposure to the Drake Chemical Company Superfund Site: Morbidity
Patterns Among Former Employees. Journal of Environmental Health,
50-389-394, 1988.
Rockette HE,
Arena VC: An Evaluation of the Proportionate Mortality
Index in the Presence of Multiple Comparisons. Statistics in
Medicine 6(1):71-77, 1987.
Enterline
PE, Marsh GM, Henderson V, Callahan C: Mortality Update
of a Cohort of U.S. Man-Made Mineral Fiber Workers. The Annals
of Occupational Hygiene, 31, 625-656, 1987.
Marsh GM,
Winwood J, Rao BR: Prediction of the Standardized Risk Ratio Via
Proportional Mortality Analysis. Biometrical Journal, 29,
355-368, 1987.
Marsh GM,
Caplan RJ: Evaluating Health Effects of Exposure to Hazardous
Waste Sites: A Review of the State-of-the-Art with Recommendations
for Future Research. In Health Effects from Hazardous Waste
Sites, Editors: J.B. Andelman and D.W. Underhill, Lewis Publishers,
Inc., Chelsea, MI, 1987.
Marsh GM,
Winwood J, Rao BR: Prediction of the Standardized Risk Ratio Via
Proportional Mortality Analysis. Biometrical Journal, 29,
355-368, 1987.
Marsh GM,
Caplan RJ: The Feasibility of Conducting Epidemiologic Studies
of Populations Residing Near Hazardous Waste Disposal Sites. In
Environmental Epidemiology, Editors: F.C. Kopfler and G.F.
Craun, Lewis Publishers, Inc., Chelsea, MI, 1986.
Matanoski G,
Fishbein L, Redmond C, Rosenkranz H, Wallace L: Contribution
of organic particulates to respiratory cancer. Environmental
Health Perspectives 70:37-49, 1986.
Rao BR, Marsh
GM, Winwood J: Sidak-Type Simultaneous Confidence Intervals
for the Measures RSMRi in Proportional Mortality Analyses
Involving Competing Risks of Death. Communications in Statistics-Theory
and Methods, 15, 515-536, 1986.
Marsh GM,
Ehland J, Paik M, Preininger M, Caplan R: OCMAP/PC: A User Oriented
Cohort Mortality Analysis Program for the IBM PC. The American
Statistician, 40, 308-309, 1986.
Savitz DA, Redmond
CK: Screening for geographic heterogeneity of disease rates:
application to cancer incidence in Allegheny County, Pennsylvania,
1969-71. Journal of Chronic Diseases 38:145-156, 1985.
Rockette HE:
Contributed Chapter 3 to 1985 Report to Surgeon General: Smoking
Related Cancer and Chronic Lung Disease in the Workplace: Evaluation
of Smoking Related Cancers in the Workplace, PP 97-135.
Fisher B, Rockette
HE, Fisher ER, Wickerham DL, Redmond C, Brown A: Leukemia
in breast cancer patients following adjuvant chemotherapy or post-operative
radiation. The NSABP experience. Journal of Clinical Oncology
3(12):1640-1658, 1985.
Rockette HE,
Redmond CK: Selection, followup and analysis in the coke
oven study. National Cancer Institute. Monogr 67:89-94,
1985.
Deutscher S,
Rockette HE, Krishnaswami V: Evaluation of habitual excessive
alcohol consumption on myocardial infarction risk in coronary
disease patients. Journal of Chronic Diseases, Vol 37,
No. 5, PP 407-415, 1984.
Deutscher S,
Rockette HE, Krishnaswami V: Correlations between habitual
excessive drinking, cigarette smoking and myocardial infarction.
American Heart Journal 108(4) Part 1, 988-995, 1984.
Ellakkani M,
Alaire Y, Weyel D, Mazumdar S, Karol M: Pulmonary Reactions
to Inhaled Cotton Dust: Animal Model for Byssinosis. Journal
of Toxicology and Applied Pharmacology, 74, 267-284, 1984.
Miller B, Mazumdar
S: MVSPEC: A User-Oriented Multivariate Spectral Analysis
Program. The American Statistician. 88, 4, 319, 1984.
Rockette HE,
Arena VC: Mortality studies of aluminum reduction plant
workers: Potroom and carbon department. JOM Vol 25, No.
7:549-557, 1983.
Redmond CK:
Cancer Mortality Among Coke Oven Workers. Environmental Health
Perspectives, 52, 67-73, 1983.
Mazumdar S,
Sussman N: Relationships of Air Pollution to Health: Results from
the Pittsburgh Study. Archives of Environmental Health,
38, 1, 17-24, 1983.
Mazumdar S,
Schimmel H, Higgins I: Relation of Daily Mortality to Air Pollution:
Analysis of 14 London Winters. 1958/59 1971/72. Archives of
Environmental Health, 37, 4, 213-220, 1982.
Marsh GM:
Computerized Approach to Verifying Study Population Data in Occupational
Epidemiology. Journal of Occupational Medicine, 24, 596-601,
1982.
Enterline
PE, Marsh GM: Cancer Among Workers Exposed to Arsenic
and other Substances in a Copper Smelter. American Journal
of Epidemiology, 116, 895-911, 1982.
Redmond CK:
Sensitive Population Subsets in Relation to Effects of Low Doses.
Environmental Health Perspectives, 42, 137-140, 1981.
Marsh GM,
Preininger ME: OCMAP: A User-Oriented Occupational Cohort Mortality
Analysis Program. American Statistician, 34, 245-246, 1980.
Mazumdar S,
Sussman N: Evidence of Possible Acute Health Effects of Ambient
Air Pollution: Results Based on Pittsburgh Area Daily Mortality
and Morbidity. Proceedings of the Park City Environmental Health
Conference: Park City, Utah, April 4-7, 1979.
Rockette HE:
Mortality studies of coal miners. Proceedings of Conference on
the Health Implications of New Energy Technologies, Park City,
Utah, April 1979.
Redmond CK,
Emes J, Mazumdar S, Magee PC, Kamon E: Mortality of Steelworkers
Employed in Hot Jobs. Journal of Environmental Pathology and
Toxicology, 2, 75-96, 1979.
Marsh GM,
Enterline PE: A Method for Verifying the Completeness of
Cohorts Used in Occupational Mortality Studies. Journal of
Occupational Medicine, 21, 665-670, 1979.
Mazumdar S,
Redmond C: Evaluating Dose-Response Relationships Using
Epidemiological Data on Occupational Groups. Proceedings of a
Conference on Environmental Health, Alta, Utah, June 26-30, 1978.
Sponsored by SIAM Institute for Mathematics and Society.
Emes J, Mazumdar
S, Redmond C, Kamon E: Models for Estimating Worksite
WBGT. American Industrial Hygiene Association Journal, 39, 592-597,
1978.
Wong O, Rockette
H, Redmond CK, Heid M: Evaluation of Multiple Causes
of Death in Occupational Mortality Studies. Journal of Chronic
Diseases, 31, 183-193, 1978.
Rockette HE:
Cause specific mortality of coal miners covered by the UMW Health
and Retirement Funds. J Occup Med Vol 19, No. 12, pp 795-801,
December 1977.
Collins J, Redmond
CK: The Use of Retirees to Evaluate Occupational Hazards.
Journal of Occupational Medicine, 18, 595-602, 1976.
Rockette,
H, Redmond CK: Long-term Mortality Experience of Steelworkers,
X. Mortality Patterns Among Masons. Journal of Occupational
Medicine, 18, 541-545, 1976.
Redmond CK,
Breslin PP: Comparison of Methods for Assessing Occupational Hazards.
Journal of Occupational Medicine, 17, 313-318, 1975.
Mazumdar S,
Redmond C, Sollecito W, Sussman N: An Epidemiological Study
of Exposure to Coal Tar Pitch Volatiles Among Coke Oven Workers.
Journal of the Air Pollution Control Association, 25, 4,
382-389, 1975.
Mazumdar S,
Lerer T, Redmond, C: Long-Term Mortality Study of Steelworkers
IX. Mortality Patterns Among Sheet and Tin Mill Workers. Journal
of Occupational Medicine, 17,12, 751-755, 1975.
Redmond CK,
Ciocco A, Lloyd JW, Rush HW: Long-term Mortality Study of Steelworkers,
VI. Mortality from Malignant Neoplasms Among Coke Oven Workers.
Journal of Occupational Medicine, 14, 621-629, 1972.
Redmond CK,
Smith EM, Lloyd JW, Rush HW: Long-term Mortality Study of Steelworkers,
III. Follow-up. Journal of Occupational Medicine, 11, 513-521,
1969.
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Occupational Cohort Mortality Analysis Program (OCMAP)
Faculty members
in the Department have also been active in the development of software
packages and data base systems for use in the occupational and environmental
epidemiology research program. The Occupational Cohort Mortality
Analysis Program (OCMAP) began in 1980 as a unified set of FORTRAN
programs for the comprehensive editing and analysis of data from
the Department's many occupational health related research projects
(Marsh and Preininger, 1980). A particular advantage of the original
OCMAP was its unique ability, compared with other programs at that
time, to relate mortality outcomes to a number and variety of exposure
metrics computed directly from detailed work service histories of
study subjects. Due to the high demand for such a comprehensive
and generalized computing resource, the Department began to distribute
and market copies of OCMAP to outside researchers in academia, government
and the private sectors. Funds obtained from sales of the program
were used for continued research and development.
In the 1980's,
OCMAP-PC, the first microcomputer version of OCMAP was created (Marsh
et al., 1986), and new analytic modules were developed by Biostatistic's
students as part of their Master's thesis requirement (Caplan et
al., 19984; Marsh et al., 1989). In the 1990's, OCMAP was redesigned
for optimal microcomputer use and extended to include many new computing
algorithms (Marsh et al., 1998). The new program, OCMAP-PLUS, offered
a comprehensive, flexible and efficient analysis of incidence or
mortality rates and standardized measures in relation to multiple
and diverse work history and exposure measures. New features included
executable code, minimization of memory requirements, disk file
storage of person-day arrays, stratified analyses by geographic
area, employment status and up to eight exposure variables, a data
imputation algorithm for study members with unknown race and enhanced
algorithms for constructing several time-dependent exposure measures.
New modules create grouped data files for Poisson and logistic regression
and risk sets files for use in relative risk regression models.
Currently, faculty
members are working on a version of OCMAP-Plus that operates efficiently
under the MS Windows ® graphical interface, and plan to release
a beta test version in early 2002. While the OCMAP programs were
designed primarily for occupational mortality studies, applications
generalize easily to studies of other health endpoints such as cancer
incidence, and to studies in non-occupational settings. OCMAP is
now in use by more than 300 institutions in the United States and
abroad. OCMAP has been referenced in more than 180 peer-reviewed
journal articles based on a review of the Science Citations Index
data base (Institute for Science Information, 1999). Further information
about OCMAP can be found in the cited articles or on the dedicated
web site: ocmap.biostat.pitt.edu.
Selected Publications
(for OCMAP section):
Marsh
GM,
Youk AO, Stone RA, Sefcik S, Alcorn C. OCMAP-Plus: A
program for the comprehensive analysis of occupational cohort data.
Journal of Occupational and Environmental Medicine 1998;40:351-362.
Marsh
GM, Co-Chien H, Rao BR, Ehland J. OCMAP: Module 6-A new computing
algorithm for proportional mortality analysis. American Statistician
1989;43:127-128.
Marsh
GM, Ehland J, Paik M, Preininger M, Caplan R. A user oriented
cohort mortality analysis program for the IBM PC. American Statistician
1986;40:308-309.
Caplan
RJ, Marsh GM, Enterline PE. A generalized effective
exposure modeling program for assessing dose-response in epidemiologic
investigations. Comput Biomed Res. 1984;16:587-596.
Marsh
GM, Preininger ME. OCMAP: A user-oriented occupational cohort
mortality analysis program. American Statistician 1980;34:
245-246.
Mortality and Population Data System (MPDS)
Also since 1980,
faculty members in the Department of Biostatistics have developed
and maintained a data repository and retrieval system for detailed
mortality data provided by the National Center for Health Statistics
and the U.S. Census Bureau. This Mortality and Population Data System
(MPDS) contains the underlying cause of death code (using International
Classification of Diseases (ICD) four-digit codes) for all persons
who died in the U.S. between 1950 and 1994 (limited to deaths from
malignant neoplasms for the 1950-61 period). Individual death records
include codes for sex, race, age of death, year of death and geographic
location (county and state of residence at time of death).
In MPDS, individual
death records are categorized and linked with the corresponding
population data to form death rates specific for five-year age groups,
five-year time periods, race (white and non-white), sex, geographic
location and cause of death. Cause of death can be defined by any
individual ICD code or combination of ICD codes. The OCMAP/MPDS
web site ocmap.biostat.pitt.edu. provides a listing of the standard
63 cause of death categories that are suitable for most cohort analyses.
The listing shows the ICD codes for the sixth through ninth revisions,
and indicates which categories can be made comparable to any one
revision using comparability ratios (CR) provided by the NCHS. This
approach, in which death rates are "adjusted" to a specific
base ICD revision, is appropriate for studies that code all deaths
to the base revision. MPDS death rates are also available in unadjusted
form. Such rates are appropriate for studies that code all deaths
to the revision of the ICD in effect at the time of death.
The MPDS standard
death rate files can be written to OCMAP-Plus format specifications
and input directly as standard population data in comparative mortality
analyses. Because of this useful feature, many users of the OCMAP
programs also request MPDS rate files for use as standard populations
in historical cohort analyses. Funds generated from sales of the
MPDS rate files are also used for continued research and development
of MPDS and OCMAP. The MPDS data base is updated annually as new
NCHS data are released. The MPDS is the most comprehensive and accessible
data repository and retrieval system of its kind in use today. Further
information about MPDS can be found in the cited articles or on
the dedicated web site: ocmap.biostat.pitt.edu.
(at this time there
are no publications for this section.)
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Radiological Imaging Systems
The Biostatistics
Department has a long standing relationship with the Department
of Radiology in studies to compare the accuracy of different diagnostic
imaging systems. The biostatistical component usually addresses
issues relative to the design, analysis and interpretation of the
study. To date, there has been collaboration on five large scale
clinical studies involving more than 20 different radiologists and
200,000 different images. These studies have included evaluating
the effects of pixel size, resolution, brightness, compression and
clinical history on the diagnostic accuracy of different imaging
modalities.
In addition to
participating in the analysis and interpretation of specific studies,
the Biostatistics Department has contributed to the improvement
of design, analysis, and interpretation of diagnostic imaging studies.
Design issues which have been addressed include the role of subtle
cases, the effect of "easy" controls, the role of stratification
in imaging studies, methods to estimate sample size, and the advantages
of a continuous scoring scale. Contributions to the improvement
in the analysis of imaging studies include methods of analyzing
studies stratified by subtlety of the case, a method of analyzing
studies with multiple readers, and a rank order method to analyze
studies with an underlying ordered parameter.
Several faculty members in the Biostatistics Department are collaborating with the PET methodology researchers in the Radiology Department in several studies involving design, analysis and interpretation of results. Special emphasis is given to methodological research for the analysis of neuroimaging data. Graduate students get opportunities to work as graduate student researchers and develop their theses.
Selected Publications:
Meltzer CC, Price JC, Mathis CA, Butters MA, Ziolko SK, Moses-Kolko E, Mazumdar S, Mulsant BH, Houck PR, Lopresti BJ, Weissfeld LA, and Reynolds CF. Serotonin 1A receptor binding and treatment response in late-life depression. Neuropsychopharmacology (in press).
Price JC, Kelley DE, Ryan CM, Meltzer CC, Drevets WC, Mathis CA , Mazumdar S, and Reynolds CF. Evidence of increased serotonin-1A receptor binding in type 2 diabetes: a positron emission tomography study. Brain Research, 2002; 927:97-103.
Price JC, Drevets WC, Ruszkiewicz J, Greer PJ, Villemagne VL, Xu L, Mazumdar S, Cantwell MN, Mathis CA.Sequential H 2 [ 15 O] pet studies in baboons: before and after amphetamine. The Journal of Nuclear Medicine, 43(8): 1090-1100, 2002.
Gur D, Rockette
HE, Armfield DR, Blachar A, Bogan JK, Brancatelli G, Britton
CA, Brown ML, Davis PL, Ferris JV, Fuhrman CR, Golla S, Katyal
S, Lamomis JM, McCook B, Thaete FL, Warfel TE. The Prevalence
Effect in a Laboratory Environment. Radiology, 228: 10-14,
2003.
Fuhrman CR, Britton
CA, Bender T, Sumkin JH, Brown ML, Holbert JM, Chang TS, Rockette
HE, Gur D: Observer Performance Studies: Detection of single
vs. multiple abnormalities of the chest. American Journal of
Roentgenology, 179(6): 1551-3, 2002.
Rockette HE,
Li W, Brown ML, Britton CA, Towers JT, Gur D. A Statistical Test
to Assess Rank Order ROC Imaging Studies. Academic Radiology
8(1):24-30, 2001.
Herron JM, Bender
T, Campbell WL, Sumkin JH, Rockette HE and Gur D: Effects
of luminance and resolution on observer performance. Radiology
215:169-174, 2000.
Good WF, Sumkin
JH, Dash N, Johns CM, Zuley ML, Rockette HE, Gur D: Observer
sensitivity to small differences: A multipoint rank-order experiment.
AJR 173: 275-278,1999.
Rockette HE,
Campbell WL, Britton CA, Holbert JM, King JL, Gur D: Empirical
assessment of parameters that affect the design of multireader
ROC studies. Academic Radiology Vol 6:723-729, 1999.
Rockette HE,
King JL, Medina JL, Eisen HB, Brown ML, Gur D: Imaging systems
evaluation: Effect of subtle cases on the design and analysis
of receiver operating characteristic studies. American Journal
of Roentgenology Vol. 165(3), 679-683, 1996.
Oliver JH, Baron
RL, Federle MP, Rockette HE: Detecting hepatocellular carcinoma:
value of unenhanced or arterial phase CT imaging or both used
in conjunction with conventional portal venous phase contrast-enhanced
CT imaging. Amer J Roentgenology 167(1):71-77, 1996.
Rockette HE,
Gur D, Kurs-Lasky M, King JL: On the generalization of the receiver
operating characteristic analysis to the population of readers
and cases with the jackknife method: An assessment. Academic
Radiology Vol 2, PP 66-69, 1995.
Obuchowski NA,
Rockette HE: Hypothesis testing of diagnostic accuracy
for multiple readers and multiple tests: An ANOVA approach with
dependent observations. Commun Statistics 24(2), 285-308,
1995.
Rockette HE,
Gur D, Campell WL, Thaete FL: Utilization of meta analysis in
the evaluation of imaging systems. Academic Radiology Vol.
1, PP 63-69, 1994.
Rockette HE:
An index for diagnostic accuracy in the multiple disease setting.
Academic Radiology Vol 1, PP 283-286, 1994.
Rockette HE,
Gur D and Metz CH: The use of continuous and discrete confidence
judgments in receiver operating characteristic studies of diagnostic
imaging techniques. Investigative Radiology 1992, 27: 169-172.
Gur D, Rockette
H, Good WF, Slasky BS, Cooperstein LA, Straub WH, Obuchowski
NA and Metz CE: Effect of Observer Instruction on ROC Study of
Chest Images. Invest Rad March 1990: Vol. 25, No. 3: 230-234.
Rockette HE,
Gur D, Cooperstein LA, Obuchowski NA, King JL, Fuhrman CR, Tabor
EK, Metz CE:iEffect of two rating formats in multi-disease ROC
study of chest images. Invest Rad March 1990: Vol. 25,
No. 3: 225-229.
Good BC, Cooperstein
LA, DeMarino GB, Miketic LM, Gennari RC, Rockette HE, Gur
D: Does knowledge of the clinical history effect the accuracy
of chest radiograph interpretation? AJR: 154, April 1990,
pg. 709-711.
Slasky BS, Gur
D, Good WF, Costa-Greco MA, Harris KM, Cooperstein LA, Rockette
HE: Receiver operating characteristic analysis of chest image
interpretation with conventional, laser printed, and high resolution
workstation images. Radiology 1990, 174: 775- 780.
Rockette HE,
Obuchowski NA, Gur D: Nonparametric estimation of degenerate ROC
data sets used for comparison of imaging systems. Invest Radiol
1990, 25: 835-837.
Gur D, King JL,
Rockette HE, Britton CA, Thaete FL, Hoy RJ: Practical issues
of experimental ROC: Selection of controls. Investigative Radiology
June 1990: Vol. 25, 583-586.
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Otolaryngology
Various manifestations
of ear disease are the most common reason (other than routine physical
examinations) that parents visit a pediatrician. Complications of
ear disease include potential hearing loss associated with fluid
in the ear which if present over long periods of time may impact
on language development. The Department of Biostatistics has a long
history of collaboration with the Department of Otolaryngology in
studies to better delineate the aetiology and treatment of ear disease
(otitis media) in children. This has entailed participation in the
design and analysis of more than two dozen studies of over 10,000
children. Studies conducted have included the evaluation of the
treatment effect of decongestant and antihistamine and various antibiotics
on the short term resolution of otitis media with effusion, the
effect of surgery and tube placement for the treatment of chronic
otitis media with effusion, and the effect of various antibiotics
on the treatment of acute otitis media (ear infection). Additional
studies have characterized both the demographic factors related
to the incidence of ear disease and the genetic component of the
disease.
The most recent
study entailed the follow-up and evaluation of more than 5,000 children
during the first two years of life of whom more than 400 children
with persistent ear disease were randomized to receive tubes immediately
or to delay for a short period to provide further opportunity for
clearance of fluid. The group with delayed tube placement had more
ear disease over the first three years but required significantly
less surgical procedures. Furthermore tests at three years of age
indicated no difference in the language development of the two groups.
Some of the collaborative
publications resulting from the effort with Children's Hospital
are as follows:
Campbell TF,
Dollaghan CA, Rockette HE, Paradise JL, Feldman HM, Shruberg
LD, Sabo D, Kurs-Lasky M. Risk Factors for Speech Delay in Three
Year Old Children. Child Development. Vol. 74 (2): 346-357,
March/April 2003.
Mandel EM, Casselbrant
ML, Rockette HE, Fireman P, Kurs-Lasky M, Bluestone CD.
Systemic Steroid For Chronic Otitis Media with Effusion in Children.
Pediatrics, 110(6): 1071-80, 2002
Paradise JL,
Feldman HN, Campbell TF, Dollagham CA, Calburen KD, Bernard BS,
Rockette HE, Janosky JE, Pitcairn DL, Sabo DL, Kurs-Lasky
M, Smith CG: Effect of Early or Delayed Insertion of Tympanostomy
Tubes for Persistent Otitis Media on Developmental Outcomes at
the Age of Three Years. New England Journal of Medicine
344(16):1179-1187, 2001.
Casselbrandt
ML, Mandel EM, Fall PA, Rockette HE, Kurs-Lasky M, Bluestone
CD, Ferrell RE: The heritability of otitis media: A twin and triplet
study. JAMA 282(22): 2125-2130, Dec 1999.
Paradise JL,
Rockette HE, Colborn DK, Bernard BS, Smith CG, Kurs-Lasky
M, and Janosky JE: Otitis media in 2253 Pittsburgh-area infants:
Prevalence and risk factors during the first two years of life.
Pediatrics 99(3):318-333, 1997.
Mandel EM, Casselbrandt
ML, Rockette HE, Bluestone CD, Kurs-Lasky M: Efficacy of
antimicrobial prophylaxis for recurrent middle ear effusion.
Pediatrics Infectious Dis J 15:1074-1082, 1996.
Casselbrandt
ML, Mandel EM, Kurs-Lasky M, Rockette HE, Bluestone CD:
Otitis Media in a population of Black American and White American
infants, 0-2 years of age. International Journal of Pediatric
Otorhinolaryngology 33, 1-16, 1995.
Mandel EM, Casselbrandt
ML, Rockette HE, Bluestone CD, Kurs-Lasky M: Efficacy of
20- vs 10-day antimicrobial treatment for acute otitis media.
Pediatrics 96, 5-13, 1995.
Casselbrant ML,
Kaleida PH, Rockette HE, Paradise JL, Bluestone CD, Kurs-Lasky
M, Nozza RJ and Wald ER: Efficacy of antimicrobial prophylaxis
and of tympanotomy tube insertion for prevention of recurrent
acute otitis media: results of a randomized clinical trial. Pediatr
Infect Dis J 11:278-286, 1992.
Mandel EM,
Rockette HE, Bluestone CD, Paradise JL and Nozza RJ: Efficacy
of myringotomy with and without tympanotomy tubes for chronic
otitis media with effusion. Pediatr Infect Dis J 11:270-277,
1992.
Mandel EM,
Rockette HE, Paradise JL, Bluestone CD and Nozza RJ: Comparative
efficacy of erythromycin-sulfisoxazole, cefaclor, amoxicillin
or placebo for otitis media with effusion in children. Pediatr
Infect Dis J 10:899-906, 1991.
Rosenfeld RM
and Rockette HE: Biostatistics in otolaryngology Journals.
Arch Otolaryngol Head Neck Surg 117:1172-1176, 1991.
Mandel EM, Rockette
HE, Bluestone CD, Paradise JL, Nozza RJ: Efficacy of Amoxicillin
with and without Decongestant/Antihistamine for Otitis Media with
Effusion in Children: Results of a Double-Blind, Randomized Trial.
New England Journal of Medicine 316:432-437, 1987.
Kaleida PH, Bluestone
CD, Rockette HE, Bass LW, Wolfson JH, Breck JM, Ubinger
EB, Rohn DD: Amoxicillin-Clavulanate Potassium Compared to Cefaclor
for Acute Otitis Media in Infants and Children. Pediatr Infect
Dis 6:265-271, 1987.
Cantekin EI,
Mandel EM, Bluestone CD, Rockette HE, Paradise JL, Stool
SE, Fria TJ, Rogers KD: Lack of efficacy of a decongestant-antihistamine
combination for otitis media with effusion ("Secretory Otitis
Media") in children: Results of a double-blind, randomized
trial. N England J of Med 308:297-30l, 1983.
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Psychiatric Research
Department of Biostatistics
started a collaboration with the Department of Psychiatry, School
of Medicine about ten years ago. Faculty members are involved in
psychiatric clinical trials in evaluating different intervention
strategies in mood disorders and sleep disorders. The biostatistical
component of the collaboration includes issues relative to the design,
analysis and interpretation of the studies. There has been participation
in the Mental Health Clinical Research Center in Late-life mood
Disorders and several NIH funded research protocol in the Departments
of Psychiatry and Radiology. Students in the Department of Biostatistics
have the opportunity of working as graduate student researchers
with psychiatric researchers and develop their thesis from research
needs in the psychiatric arena. The statistical methodologies needed
in this area are mostly: survival analysis, longitudinal data analysis,
factor analysis and structural equations modeling. Recent efforts
have started to develop the analysis of fMRI and PET data as they
are used in psychiatric clinical trials.
Selected Publications:
Liu K, Stone RA, Mazumdar S , Houck PR, Reynolds CF. Covariate measurement error in the Cox model: a simulation study. Communications in Statististics (in press) .
Houck PR, Mazumdar S , Sengul TK, Tang G, Mulsant BH, Pollock BG, Reynolds CF. Estimating treatment effects from longitudinal clinical trial data with missing values: comparative analyses using different approaches. Psychiatric Research (in press).
Mazumdar S , Dew MA, Houck PR, and Reynolds CF. Assessing intra-individual changes in health related quality of life data in psychiatric clinical trials. ENVIRONMETRICS , 15, 491-499, 2004.
Houck PR, Mazumdar S , Mulsant BH, Pollock BG, Dew MA, and Reynolds CF. An intent to treat method for enhancing analysis of clinical trials with rescue medication: a mixed-model approach. Psychopharmacology Bulletin. 2003-Vol 37(1), 79-89.
Mazumdar S , Houck PR, Liu KS , Mulsant BH, Pollock, BG, Dew MA and Reynolds CF. Intent-to-treat analysis for clinical trials: use of data collected after termination of treatment protocol. Journal of Psychiatric Research , 2002, 36, 153-164.
Mazumdar S, Berhane Z, Weissfeld L, Begley A, Dew MA, Houck PR and Reynolds CF. Survival models with time-varying coefficients: A flexible approach to the analysis of psychiatric survival data. Psychopharmacology Bulletin. Autumn 2002-Vol 36(4), pp. 84-91.
Kowalski J, Tu
XM, Begley A, Houck P, Mazumdar S, Miewald J, Buysse DJ,
and Kupfer DJ. Data recycling: a response to the changing technology
from the statistical perspective with application to psychiatric
sleep. Journal of the Royal Statistical Society, Series C (Applied
Statistics), 2001, 28(8):1029-1049..
Kastango KB,
Kim Y, Dew MH, Mazumdar S, Mulsant BH, Rosen J, Reynolds
CF, Pilkonis PA and Pollock BG. Verification of a scale sub-domain
in elderly patients with dementia: a confirmatory factor analytic
approach. American Journal of Geriatric Psychiatry, 2002, 10:706-14.
Liu K, Mazumdar
S, Stone RA, Dew MA, Houck PR and Reynolds CF. Accounting
for covariate measurement error in a Cox model analysis of recurrence
depression. Journal of Psychiatric Research, 35: 177-185,
2001.
Mazumdar S,
Houck PR and Reynolds CF. Statistics in Psychiatric Research.
Hand Book of Statistics, Vol. 18. Bio-environmental and Public
Heath Statistics. Editors: P. K. Sen and C.R. Rao. 2000 Elsiever
Science, pp 1005-1026.
Pollock BG, Ferrell
RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, Davis S,
Kirshner MA, Houck PR, Stack JA, Reynolds CF and Kupfer DJ. Allelic
Variation in the Serotonin Transporter Promoter Affects Onset
of Paroxetine Treatment Response in Late-Life Depression. Neuropsychopharmacology,
23(5), 587-590, 2000.
Mazumdar S,
Liu K, Ahnn S, Houck PR, and Reynolds CF. Transition (Markov)
models for the analysis of survival times in clinical psychiatric
research. Communications in Statistics-Simulations, 28(1),
165-176, 1999.
Mazumdar S,
Liu K, Houck PR, and Reynolds CF. Intent-to-treat analysis for
longitudinal clinical trials: coping with the challenge of missing
values. Journal of Psychiatric Research, 33, 87-95, 1999.
Mazumdar S,
Begley A, Houck PR Yang Y, Reynolds CF and Kupfer DJ. Residual
Analysis in Random Regression using SAS and S-PLUS. Computer
Methods and Programs in Biomedicine, 58, 281-282, 1999.
Reynolds CF,
Frank E, Perel J, Imber SD, Cornes Cleone, Miller MD, Mazumdar
S, Houck PR, Dew MA, Stack JA, Pollock BG, Kupfer DJ. Nortriptyline
and interpersonal psychotherapy as maintenance therapies for recurrent
major depression: a randomized controlled trial in patients older
than 59 years. Journal of the American Medical Association,
281(1), 1999.
Rosen J, Bobys
PD, Mazumdar S, Mulsant BH, Sweet RA, Yu K, Kollar M, and
Pollock BG. OBRA regulations and neuroleptic use: defining agitation
using the Pittsburgh Agitation Scale and the Neurobehavioral Rating
Scale. Annals of Long-term Care, 7(12) 429-436, 1999.
Reynolds CF,
Frank E, Perel JM, Mazumdar S, and Kupfer D. Maintenance
Therapies for Late-Life Recurrent Major Depression: Research and
Review Circa 1996. In: Geriatric Psychopharmacology (Ed. Nelson,
JC). Marcel Dekker, Inc, New York, 1998.
Mulsant BH, Mazumdar
S, Pollock BG, Sweet RA, Rosen J and Lo K. Methodological
issues in characterizing treatment response in demented patients
with behavioral disturbances. International Journal of Geriatric
Psychiatry, 12:537-547, 1997.
Nowell PD, Mazumdar
S, Buysse DJ, Mary Amanda Dew, Reynolds CF, and Kupfer DJ.
Benzodiazepines and Zolpidem for Chronic Insomnia: A Meta-Analysis
of Treatment Efficacy. Journal of the American Medical Association,
278 (24), 2170-2177, 1997.
Mazumdar S,
Reynolds CF, Houck PR, Frank E, Dew MA, and Kupfer DJ. Quality
of Life in elderly patients with recurrent major depression: A
Factor Analysis of the General Life Functioning (GLF) Scale. Psychiatry
Research, 63, 183-190, 1996.
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Oncology Thinking Cap (OncoTCap)
The Oncology Thinking
Cap (OncoTCap) computer program developed by Dr. Roger Day under
NCI grant R25-CA63548 represents the behavior of individual cancer
cells in heterogeneous tumors and calculates simulations of populations
of cancer patients treated with specific regimens. The modeling
architecture of the simulation engine supports integration of processes
at many scales, including molecular functional networks, micro-environmental
interactions, functioning of physiologic systems, measurement processes,
patient management plans, patient-doctor relations, and clinical
trials design and execution. In its current level of maturity, applications
to cancer professional education have been built, deployed and utilized
in settings from middle school through medical school, oncology
fellowship programs and a national cancer pharmacology workshop.
Currently in development
is a comprehensive software-based cancer model development and validation
facility, in which the simulation engine is at the core. The purpose
requires some explanation. In many areas of controversy in cancer
treatment, clinical research is inconclusive. Pre-clinical studies
could in principle contribute to clarifying the issues. However,
the relevant literature is voluminous and ever-growing, the number
of postulated mechanisms is large, and the relevance of pre-clinical
information is always suspect. Complicating interpretation further,
many observations suggest strong connections between the postulated
mechanisms and molecular networks affecting cell cycle regulation,
signal transduction, apoptosis, invasiveness, and angiogenesis.
Finally, tumor heterogeneity repeatedly appears as a key complication.
(In fact cancer mortality generally stems from metastasis, whose
essence is spatial heterogeneity). This puts great demands on the
intuition and interpretational powers of breast cancer scientists;
single tissue samples can mislead when clonal evolution, natural
selection prior to diagnosis, and selection by treatment cause spatial
and temporal shifts in cancer cell genotype and phenotype. All these
factors interfere with making the best use of all available research
information.
Given a cancer
management problem statement, the new system will support the gathering
and assessment of relevant research information, followed by translation
of some of this information into model-specification programming
statements, translation of others into validation suites of observations
with goodness-of-fit criteria. The simulation engine can then generate
predictions, the comparisons with observations in the validation
suite assessed, and the resulting goodness-of-fit measures assembled
into a validation report card. Suitable models would then be selected
based on the specific purpose in light of the report card. The ultimate
result will be the intelligent planning, design and selection of
new treatment regimens to test clinically. A longer term goal would
be the design of biologically individualized treatment plans.
Selected Publications:
Hmelo CE, Ramakrishnan,
Day RS, Shirey WE, Brufsky A, Johnson C, Baar J, Huang,
Q. The Oncology Thinking Cap: Scaffolded use of a simulation to
learn clinical trial design. Teaching and Learning Medicine,
13(3), 2001.
Hmelo CE, Nagarajan
A, and Day RS. Effects of high and low prior knowledge
on construction of a joint problem space. Journal of Experimental
Education 69:36-56, 2000.
Hmelo C and Day
R. Contextualized questioning to scaffold learning from simulations.
Computers & Education 32:151-164, 1999.
Day R,
Shirey W, Ramakrishnan S, Huang Q. Tumor biology modeling workbench
for prospectively evaluating cancer treatments. Proceedings
of the CESA '98 IMACS Multiconference. April 1998.
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Biostatistics Facility of the University of Pittsburgh Cancer Institute
The Biostatistics Facility provides clinical and basic-science investigators in the University of Pittsburgh Cancer Institute (UPCI) with statistical and computer-related expertise in design, execution, analysis, and reporting of cancer-related research studies. These cover basic-science studies; phase I and phase II oncology clinical trials; epidemiologic studies, including those related to cancer prevention and awareness; and investigations of behavioral and health sequelae of cancer treatment. Statisticians serve on UPCI's Clinical Research Oversight Committee, Protocol Review Committee, and Data and Safety Monitoring Committee. They support the training of students, fellows, and cancer researchers in biostatistics, clinical trials, and tumor dynamics. The Facility is also committed to applying statistical and computational methods to improve the manner in which clinical trials and translational research are performed at UPCI, and to developing statistical methodology that aids cancer research. Methodologic research in the Facility has focused on the analysis of biomarkers for prognosis and prediction of response to treatment; quality control in immunologic assay systems; adaptive dose-finding techniques for phase I trials; permutation tests for logistic regression, and for inference from small datasets with many covariates; stochastic modeling of tumor growth and metastasis; weakest-link modeling for studying cause-effect in biological and medical phenomena; meta-analysis; and evaluating quality of life, and behavioral and health outcomes, of patients undergoing cancer treatment.
The Biostatistics Facility is the home of the Educational Resource for Tumor Heterogeneity (ERTH), an NCI-funded project to develop a biomathematical modeling system for oncology: the Oncology Thinking Cap simulator (OncoTCap). This software simulates the evolution of heterogeneous tumors based on mathematical and stochastic modeling of mechanisms arising from molecular biology. The growth, metastasis, and differential response of cancer cells to various treatments can be simulated, thereby providing an assessment of the therapeutic potential of alternative treatment regimens.
The Biostatistics Facility of UPCI is complemented by the Biostatistical Center for the National Surgical Adjuvant Breast and Bowel Project, a cooperative clinical trials group that conducts randomized phase III clinical trials for the prevention and treatment of breast and colorectal cancer.
Selected References
Allegra CJ, Paik
S, Colangelo LH, Parr AL, Kirsch I, Kim G, Klein P, Johnston PG,
Wolmark N, Wieand S. Prognostic value of thymidylate synthase,
Ki-67 and p53 in patients with Dukes' B and C colon cacner: an
NCI-NSABP collaborative study. J Clin Oncol, 21:241-250,
2003.
Kunkel M, Reichert
TE, Benz P, Lehr HA, Jeong JH, Wieand S, Bartenstein
P, Wagner W, Whiteside T. Overexpression of Flut-1 and increased
glucose metabolism in the tumor are associated with poor prognosis
in oral squamous cell carcinoma. Cancer, 97:1015-1024,
2003.
Grumbach M, Biller
B, Braunstein G, Campbell K, Carney J, Godley P, Harris E, Lee
J, Oertel Y, Posner M, Schlechte J, Wieand H. Management
of the clinically inalpparent adrenal mass ("Incidentaloma").
Annals of Internal Medicine, 138:424-429, 2003.
Zarour HM, Maillere
B, Brusic V, Coval K, Willams E, Pouvelle-Moratille S, Castelli
F, Land S, Bennouna J, Logan T and Kirkwood JM. NY-ESO-1
119-143 is a promiscuous MHC class II T-helper epitope recognized
by Th1 and Th2-type tumor-reactive CD4+ T cells. Cancer Res.,
Jan 1; 62(1):213-8, 2002.
Muindi JR, Yibing
P, Potter DM, Tauch JS, Capozzoli MJ, Egorin MJ, Johnson
CD, Trump DL. Pharmacokinetics of High Dose, Oral Calcitriol:
Results Obtained During a Phase One Trial of Calcitriol and Paclitaxel.
Clinical Pharmacology and Therapeutics, 72:648-659, 2002.
Zamboni WC, Gervais
AC, Egorin MJ, Schellens JH, Hamburger DR, Delauter BJ, Grim A,
Zuhowski EG, Joseph E, Pluim D, Potter DM, Eisenman JL.
Inter- and intratumoral disposition of platinum in solid tumors
after administration of cisplatin. Clinical Cancer Research,
8(9):2992-2999, 2002.
Brissette-Storkus
CS, Kettel JC, Whitham TF, Giezeman-Smits KM, Villa LA, Potter
DM, Chambers WH. Flt-3 ligand (FL) driver differentiation
of rat bone marrow-derived dendritic cells expressing OX62 and/or
CD161 (NKR-P1). Journal of Leukocyte Biology, 71(6):941-949,
2002.
Kirkwood JM,
Richards T, Zarour HM, Sosman J, Ernstoff M, Whiteside T, Ibrahim
J, Blum R, Wieand S, Mascari R. Immunomodulatory Effects
of High- and Low-dose IFNalpha2b in Patients with High-risk Resected
Melanoma: The E2690 Laboratory Corollary of Intergroup Adjuvant
Trial E1690. Cancer, 95: 1101-1112, 2002.
Matin K, Egorin
MJ, Bellesteros MF, Smith DC, Lembersky B, Day RS, Johnson
CS, Trump DL. Phase I and Pharmacokinetic study of vinblastine
and high dose megestrol acetate. Cancer Chemotherapy &
Pharmacology, 50(3):179-85, 2002.
Rose C, Green
M, Webber S, Kingsley L, Day R, Watkins S, Reyes J, Rowe
D. Detection of Epstein-Barr virus genomes in peripheral blood
B cells from solid organ transplant recipients by fluorescent
in situ hybridization. Journal of Clinical Microbiology,
40(7):2533-44, 2002.
Hmelo CE, Nagarajan
A, and Day RS. It's harder than we thought it would be:
A comparative case study of expert-novice experimentation strategies.
Science Education, 219-243, 2003.
Reichert TE,
Scheuer C, Day R, Wagner W, Whiteside TL. The number of
intratumoral dendritic cells and zeta-chain expression in T cells
as prognostic and survival biomarkers in patients with oral carcinoma.
Cancer 91(11):2136-2147, 2001.
Zamboni
WC, Egorin MJ, Van Echo DA, Day RS, Meisenberg BR, Brooks
SE, Doyle LA, Nemieboka NN, Dobson JM, Tait NS, Tkaczuk KH. Pharmacokinetic
and pharmacodynamic study of the combination of codetaxel and topotecan
in patients with solid tumors. J Clin Oncol 18(18):3288-3294,
2000.
Bahri S, Agarwala
S, Cano E, Johnson J, Myers E, Jeong J et al. Phase II study
of concurrent carboplatin and paclitaxel with radiation therapy
in patients with locally advanced, inoperable squamous cell carcinoma
of the head and neck (HNSCC). Proceeding of the American Society
of Clinical Oncology (ASCO), 2000.
Ball ED, Wilson
J, Phelps V, Neudorf S. Autologous bone marrow transplantation
for acute myeloid leukemia in remission or first relapse using monoclonal
antibody-purged marrow: results of Phase II studies with long-term
follow-up. Bone Marrow Trans 25:823-829, 2000.
Wilson JW,
Kim HT. Biostatistics. In Practical Guide to Bone Marrow Transplantation
(Ball ED, Lister J, Law, P, eds., WB Saunders Co) 2000.
Faul C, Gerszten
K, Edwards R, Land S, D'Angelo G, Kelly III J, Price F. A
Phase I/II study of hypofractionated whole abdominal radiation therapy
in patients with chemoresistant ovarian carcinoma: impact on quality
of life. Int J Radiat Oncol Biol Phys 1:47(3), 749-754, 2000.
Konety BR, Nguyen
TT, Brenes G, Sholder A, Lewis N, Bastacky S, Potter DM,
Getzenberg RH. Clinical usefulness of the Novel Marker BLCA-4 for
the detection of bladder cancer. J Urology 164:634-639, 2000.
Smith DC, Johnson
CS, Freeman CC, Muindi J, Wilson JW, Trump DL. A Phase I
trial of calcitroil (1,25 Dihydroxycholecalciferol) in patients
with advanced malignancy. Clin Cancer Res 5:1339-1345, 1999.
DeMagalhaes-Silverman
M, Donnenberg AD, Lister J, Rybka W, Wilson J, Ball E. Factors
influencing mobilization and engraftment in patients with metastatic
breast cancer undergoing peripheral blood stem cell transplantation.
J Hematotherapy 8:167-172, 1999.
Martin JA, Slivka
A, Rabinovitz M, Carr BI, Wilson J, Silverman WB. ERCP and
stent therapy for progressive jaundice in hepatocellular carcinoma:
which patients benefit, which patients don't? Digestive Dis &
Sci 44:1298-1302, 1999.
Shpilberg O, Wilson
J, Whiteside TL, Herberman RB and the Pittsburgh PTLD study
group. Pre-transplant immunological profile and risk factor analysis
of post-transplant lymphoproliferative disease development: the
results of a nested matched case-control study. Leuk & Lymphoma
36:109-121, 1999.
Hmelo C and
Day R. Contextualized questioning to scaffold learning from
simulations. Computers & Educ 32:151-164, 1999.
Belani CP, Aisner
J, Ramanathan R, Jett J, Greenberger J, Day R, Capazolli
MJ, Hiponia D, Engstrom C. Paclitaxel and carboplatin with simultaneous
thoracic irradiation in regionally advanced non-small cell lung
cancer. Seminars Rad Oncol 7(2):S1-S11-S13-S14, 1999.
Belani CP, Luketich
JD, Landreneau RJ, Kim R, Ramanathan RK, Day R, Ferson PF,
Keenan RJ, Posner M, Seger J, Lembersky B. Efficacy if cisplatin,
5-fluorouracil, and paclitaxel regimen for carcinoma of the esophagus.
Seminars Rad Oncol 1998.
Adedoyin A, Stiff
DD, Smith DC, Romkes M, Bahnson RC, Day R, Hofacker J, Branch
RA, Trump DL. All-trans-retinoic acid modulation of drug-metabolizing
enzyme activities: Investigation with selective metabolic drug probes.
Cancer Chemo & Pharm 41:133-139, 1998.
Day R, Shirey
W, Ramakrishnan S, Huang Q. Tumor biology modeling workbench for
prospectively evaluating cancer treatments. Proc CESA 98 IMACS
Multiconference, April 1998.
Reichert TE, Day
RS, Wagner EM, Whiteside TL. Absent or low expression of the
zeta chain in T cells at the tumor site correlates with poor survival
in patients with oral carcinoma. Cancer Res 58(23):5344-5347,
1998.
Grandis JR, Melhem
MF, Gooding WE, Day R, Holst VA, Wagener MM, Drenning SD,
Tweardy DJ. Tumor levels of TGF and EGFR protein predict survival
in patients with head and neck squamous call carcinoma. J Natl
Cancer Inst 90(11):824-832, 1998.
Pitman KT, Johnson
JT, Edington H, Barnes EL, Day R, Wagner RL, Myers EN. Lymphatic
mapping with isoulfan blue dye in head and neck squamous cell carcinoma.
Arch Ontolaryn Head Neck Surg 124(7):790-793, 1998.
Kirkwood J, Bryant
J, Schiller JH, Oken MM, Borden EC, Whiteside TL. Immunomodulatory
function of interferon gamma in patients with metastatic melanoma:
Results of a Phase IIB trial in subjects with metastatic melanoma:
ECOG Study 4987. J Immunotherapy 20(2):146-157, 1997.
DeMagalhaes-Silverman
M, Lister J, Rybka W, Wilson J, Ball E. Busulfan and cyclophosphamide
(BU/CY2) as preparative regimen for patients with lymphoma. Bone
Marrow Trans 19:777-781, 1997.
Kirkwood JM, Wilson
JW, Whiteside TL, Donnelly SL, Herberman RB. Phase Ib trial
of Picibanil (OK-432) an as immunomodulator in patients with resected
high-risk melanoma. Cancer Immun Immunother 44:137-149, 1997.
DeMagalhaes-Silverman
M, Bloom E, Lembersky B, Lister J, Pincus S, Rybka W, Voloshin M,
Wilson J, Ball E. High dose chemotherapy and autologous stem
cell support followed by posttransplant doxorubicin as initial therapy
for metastatic breast cancer. Clin Cancer Res 3:193-197,
1997.
Kozii R, Wilson
J, Persichetti J, Phelps V, Ball SEB, Ball ED. THY-1 Expression
on blast cells from adult patients with acute myeloid leukemia.
Leukemia Res 21:381-85, 1997.
Trump DL, Smith
DC, Stiff D, Adedoyin A, Day R, Bahnson RR, Hofacker J, Branch
RA. A Phase II trial of all-trans-retinoic acid in hormone-refractory
prostate cancer: A clinical trial with detailed pharmacokinetic
analysis. Cancer Chemo & Pharm 39(4):349-356, 1997.
Belani CP, Luketich
JD, Landreneau RJ, Kim R, Ramanathan RK, Day R, Ferson PF,
Keenan RJ, Posner M, Seger J, Lembersky B. Efficacy if cisplatin,
5-fluorouracil, and paclitaxel regimen for carcinoma of the esophagus.
Seminars Oncol 24(6):S-19-89-S19-92, 1997.
Getzenberg RH,
Light BW, Lapco PI, Konety BR, Nangia AK, Acierno JS, Chir R, Shurin
Z, Day RS, Trump DL, Johnson CS. Vitamin D inhibition of
prostate adenocarcinoma growth and metastasis in the Dunning rat
prostate model system. Urology 50(6):999-1006, 1997.
Belani CP, Aisner
J, Bahri S, Jett J, Day R, Capazolli MJ, Hiponia D, Engstrom
C. Chemotherapy in non-small cell lung cancer: Pacitaxel/carboplatin/radiotherapy
in regionally advanced diseases. Seminars Oncol 23(6 Suppl
16):113-116, 1996.
Shpilberg O, Wilson
J, Green M, Nalesnik M, Day R, Herberman RB, Whiteside T.
The role of immunological effector-cells in the development of post-transplant
lymphoproliferative disorders (PTLD). Blood 86(10)[1]:1354,
1995.
Osborn JL, Schwartz
GG, Smith DC, Bahnson R, Day R, Trump DL. Phase II trial
of oral 1,25-dihydroxyvitamin d (calcitriol) in hormone refractory
prostate cancer. Urologic Oncol 1:195-198, 1995.
Nanmark U, Johansson
BR, Bryant JL, Unger ML, Hokland ME, Goldfarb RH, Basse PH.
Microvessel origin and distribution in pulmonary metastases of the
B16 melanoma: Implications for adoptive immunotherapy. Cancer
Res 55:4627-4632, 1995.
Appasamy R, Bryant
J, Hassanein T, Van Thiel DH, Whiteside TL. Effects of therapy
with alpha interferon on peripheral blood lymphocyte subsets and
their cytotoxicity in patients with chronic hepatitis C. Clin
Immun Immunopath 73(3):350-357, 1994.
Whiteside TL, Letessier
E, Hirabayashi H, Vitolo D, Bryant J, Barnes L, Snyderman
C, Johnson JT, Myers E, Herberman RB, Rubin J, Vlock DR. Evidence
for local and systemic activation of immune cells in the Phase Ib
trial of peritumoral injections of interleukin 2 in patients with
advanced squamous cell carcinoma of the head and neck. Cancer
Res 53:5654-5662, 1993.
Logan TF, Bryant
J, Shannon W, Kane P, Wolmark N, Posner M, Kirkwood JM, Ernstoff
M, Futrell JW, Dexter-Straw L, Iwatuski E, Bahnson R. Preparation
of viable tumor cell vaccine from human solid tumors: Relationship
between tumor and cell yield. Melanoma Res 3:451-455, 1993.
Goldberg J, Gryn
J, Raza A, Bennet J, Browman G, Bryant J, Grunwald H, Larson
R, Vogler R, Preisler H. Mitoxantrone and 5-azacytidine for refractory/relapsed
ANLL or CML in blast crisis: A leukemia intergroup study. Amer
J Hemat 43:286-290, 1993.
Gollin SM, Bruno
MA, Law J, Ferrell RE, Bryant JL, Johnson JT, Myers EN, Barnes
EL, Rossie KM. TP53 abnormalities in oral squamous cell carcinoma.
Amer J Human Gen 53(3):303, 1993.
Lese CM, Rossie
KM, Appel BN, Johnson JT, Myers EN, Bryant JL, Gollin SM.
Aneuploidy in oral squamous cell carcinoma. Amer J. Human Gen
53(3):322, 1993.
Kirkwood JM, Wilson
J, Whiteside TL, Bryant J, Vlock DR, Straw L, Herberman RG.
Antitumor and immunomodulatory effects of intradermal picibanil
(OK-432): Results of a Phase IB trial in high risk melanoma. Cancer
Invest 10:20-21, 1992.
Larson RA, Day
RS, Axarnia N, Bennett JM, Browman G, Goldberg J, Gottlieb A,
Grunwald H, Miller K, Raza A, Vogler R, Winto E, Preisler H. The
selective use of amsa following high-dose cytarabine in patients
with acute myeloid leukaemia in relapse. Brit J Hema 82:337-346,
1992.
Ernstoff MS, Gooding
W, Nair S, Bahnson RR, Miketic LM, Banner B, Day R, Whiteside
TL, Titus-Ernstoff L, Kirkwood JM. Immunological effects of treatment
with sequential administration of recombinant interferon gamma and
alpha in patients with metastatic renal cell carcinoma during a
phase I trial. Cancer Res 52:91-103, 1992.
Logan T, Kaplan
S, Bryant J, Ernstoff M, Krause M, Kirkwood J. Granulocytopenia
in cancer patients treated in a Phase I trial with recombinant human
tumor necrosis factor (TNF). J Immunotherapy 10:84-95, 1991.
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