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· Dynamic
treatment sequencing |
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Dynamic treatment sequencing ·
Skew-symmetric distributions ·
Bariatric
Surgery ·
Alzheimer’s
research |
· Invited · Others |
|
Treatment of complex diseases such as cancer, leukemia, AIDS and depression usually follows complex treatment regimes consisting of a sequence of pre- and post-remission therapies. An adaptive treatment strategy (ATS), sometimes referred to as a dynamic treatment regime is a sequence of individually tailored treatments. Under an ATS, during the treatment period individuals receive time-varying treatment based on their health status and other eligibility criteria specified prior to the start of the treatment. An example might be the cases where patients are treated with one of several available treatments (or different doses of same drug) for a fixed period of time and then based on the intermediate response are switched to a different treatment. Another example of the application of such dynamic treatment regime is where patients receive an induction therapy and among those who achieve remission receive some form of maintenance therapy.
While making treatment decisions at each stage, a physician looks at multiple factors including (i) treatments assigned in prior stages (ii) response to the treatments in prior stage (iii) health status (quality of life) of the patient and (iv) possible treatments the patient is eligible for at that particular stage. The goal at each stage is to decide on the treatment which will result in largest short/long-term benefit. If the number of stages and the number of treatment options at each stage are small, sequential multiple assignment randomization trials could be used to compare different treatment strategies. My main research interest is efficient estimation of survival distributions under treatment strategies and comparison of multiple treatment strategies based on observational or randomized studies.
In the year 2007, we have formed a reading group to accelerate our research in this area. Please visit the reading group website Adaptive Treatment Strategy Reading Group.
Feng, W and
Feng, Wentao and
Wahed, AS and Tsiatis, A. A (2004). Optimal estimator for the survival distribution and related quantities for treatment policies in two-stage randomization designs in clinical trials, Biometrics, March 2004, Vol. 60, No. 1. pp 124-133.
In review:
Feng, W and
In recent years, there has been considerable interest among
investigators in the construction of general class of skewed distributions
which includes the standard symmetric distributions such as the normal, t,
logistic and Cauchy distributions. The key is to introduce additional
parameters or parametric functions in the distributional form that accounts for
the skewness of the distribution. The idea became
institutionalized when Azzalini (1985) defined a class
of distribution (which he referred to as skew-normal) by introducing an
additional skewness parameter that included the
normal distribution as a special case. The name suggests that this
distribution, unlike the normal distribution, is asymmetric in general and
allows both positively and negatively skewed distributions. Subsequently, Azzalini and Dalla Valle (1996)
came up with the multivariate version of the skew-normal distribution. A
statistical application of the multivariate skew-normal distribution was
considered by Azzalini and Capitanio
(1999). This paper popularized the application of such distributions and led
the way for others to define similar families of distributions based on other
symmetric distributions such as skew-Cauchy (
Ali,
MM, Woo, J, Pal, M and
Wahed, Abdus. (2007) The family of curvi-triangular distributions. International Journal of Statistical Sciences, Vol. 3, pp. 7-18.
Wahed, Abdus. (2006) Bayesian Inference Using Burr Model Under Asymmetric Loss Function: An Application to Carcinoma Survival Data. Journal of Statistical Research, 2006, Vol. 40, No. 1, pp. 45-57.
Wahed, Abdus. (2006). A General Method of Constructing Extended Families of Distributions from an Existing Continuous Class. Journal of Probability and Statistical Science 4(2), 165-177.
Wahed, Abdus and Ali, M. Masoom. The Skew-Logistic Distribution. Journal of Statistical Research, 2001, Vol. 35, No,2, pp. 71-80.
In review:
My research with HCV is a result of my collaboration in the
clinical trials/studies coordinated by the
In addition, currently I am a co-investigator in a Phase I/II clinical trial (SYNCH) sponsored by NIDDK and NCAM to investigate the safety and efficacy of silymarin as a treatment for hepatitis C.
Hoofnagle, JH, Wahed,
AS, Brown, RS, Howell, CD, Belle, SH for the Virahep-C
Study Group (2008). Early
Changes in Hepatitis C Viral Levels in Response to Peginterferon and Ribavirin in Patients with Chronic Hepatitis C, Genotype 1
Infection, accepted, Journal of Infectious Diseases.
Golden-Mason, L, Klarquist, J,
Dowling, TC, Wahed, AS, Paul, M, Terrault, NA, Taylor, M, Jeffers, L, Hoofnagle, JH, and Howell, CD for the Virahep-C Study Group (2008). Peginterferon Pharmacokinetics in African American and Caucacian American Patients with Hepatitis C Virus Genotype 1 Infection, CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:575–583.
Smith, SR, Wahed, AS, Kelley, SS, Conjeevaram, HS, Robuck, PR, Fried, MR for the Virahep-C Study Group (2007). Assessing the Validity of Self-Reported Medication Adherence in HCV Treatment. Annals of Pharmacotherapy, 41: 1116-1123.
Brodsky, LI,
Donlin, MJ, Cannon, NA,
Yee, LJ, Tang, Y, Kleiner, DE, Wang, D, Im, K, Wahed, AS, Tong, X, Rhodes, S, Su, X, Whelan, RM, Fontana,RJ, Ghany, MG, Borg, B, Liang, TJ, Yang, H for the Virahep-C Study Group (2007). Myxovirus-1 and protein kinase haplotypes and fibrosis in chronic hepatitis C virus (p NA). Hepatology, 2007, 46 (1): 74-83.
Conjeevaram HS, Kleiner DE, Everhart JE, Hoofnagle JH, Zacks S, Afdhal NH, Wahed AS for the Virahep-C Study Group (2007). Race, Insulin Resistance and Hepatic Steatosis in chronic hepatitis C. Hepatology. 2007 Jan;45(1):80-7
The Longitudinal Assessment of Bariatric Surgery (LABS) is a National Institutes of Health (NIH)-funded consortium of six clinical centers and a data coordinating center working in cooperation with NIH scientific staff to plan, develop, and conduct coordinated clinical, epidemiological, and behavioral research in the field of bariatric surgery. Recently I joined this group as a statistician.
Recently I started collaborating with Clinical Research, Investigation, and Systems Modeling of Acute Illness Laboratory (CRISMA) as a statistician. CRISMA is directed by Derek C. Angus MD, MPH, and co-directed by Gilles Clermont MD, MSc. This large team of clinicians, mathematicians, and epidemiologists enjoys superb funding from the NIH and multiple industrial sponsors. Regarded by many around the world as the leading investigative team carrying out studies of the clinical epidemiology of critical illness, Dr. Angus and his colleagues are actively studying the genetics of human sepsis, a syndrome that affects about 750,000 Americans every year and carries a mortality rate of almost 30 percent. Dr. Angus and his team of scientists have published papers in leading journals such as JAMA, Lancet, Critical Care Medicine, and the American Journal of Respiratory and Critical Care Medicine. I mainly collaborate with John Kellum in HIDONOR and MONiTOR study.
Murugan, R, Venkataraman, R, Wahed, AS, Elder, M, Hergenroeder, G, Carter, M, Madden, NJ, Powner, D, Kellum, JA On behalf of the HIDonOR Study Investigators (2008). Increased plasma IL-6 in donors is associated with lower recipient hospital-free survival after cadaveric organ transplantation. Crit Care Med 2008; 36:1810–1816.
1.
2.
Feng, W and
3. Hoofnagle, JH, Wahed, AS, Brown, RS, Howell, CD, Belle, SH for the Virahep-C Study Group (2008). Early Changes in Hepatitis C Viral Levels in Response to Peginterferon and Ribavirin in Patients with Chronic Hepatitis C, Genotype 1 Infection, accepted, Journal of Infectious Diseases.
4. Ling, B, Schoen, RE, Trauth, JM, Wahed, AS, Eury, T, Simak, DM, Solano, FX, and Weissfeld, JL (2008).Physicians Encouraging Colorectal Screening (PECS): A randomized controlled trial of enhanced office and patient management on compliance with colorectal cancer screening, Accepted, Archives of Internal Medicine.
5. Murugan, R, Venkataraman, R, Wahed, AS, Elder, M, Hergenroeder, G, Carter, M, Madden, NJ, Powner, D, Kellum, JA On behalf of the HIDonOR Study Investigators (2008). Increased plasma IL-6 in donors is associated with lower recipient hospital-free survival after cadaveric organ transplantation. Crit Care Med 2008; 36:1810–1816.
6.
Golden-Mason, L, Klarquist,
J,
7. Dowling, TC, Wahed, AS, Paul, M, Terrault, NA, Taylor, M, Jeffers, L, Hoofnagle, JH, and Howell, CD for the Virahep-C Study Group (2008). Peginterferon Pharmacokinetics in African American and Caucacian American Patients with Hepatitis C Virus Genotype 1 Infection, CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:575–583.
8.
Ali, MM, Woo,
J, Pal, M and
9.
10.
Donlin, MJ, Cannon, NA,
11. Brodsky LI, Wahed AS, Li J, Tavis JE, Tsukahara T, et al (2007) A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients. PLoS ONE 1(1): e584. doi:10.1371/journal.pone.0000584
12. Smith, SR, Wahed, AS, Kelley, SS, Conjeevaram, HS, Robuck, PR, Fried, MR for the Virahep-C Study Group (2007). Assessing the Validity of Self-Reported Medication Adherence in HCV Treatment. Ann Pharmacother.2007; 41: 1116-1123.
13. Yee, LJ, Tang, Y, Kleiner, DE, Wang, D, Im, K, Wahed, AS, Tong, X, Rhodes, S, Su, X, Whelan, MR, Ghany, MG, Borg, B, Fontana, RJ, Liang, J and Yang, H for the Virahep-C Study Group (2007). Mxyovirus-1 (Mx1) and protein kinase (PKR) haplotypes and fibrosis in chronic HCV, Hepatology, 2007, 46 (1): 74-83.
14. Conjeevaram HS, Kleiner DE, Everhart JE, Hoofnagle JH, Zacks S, Afdhal NH, Wahed AS for the Virahep-C Study Group (2007). Race, Insulin Resistance and Hepatic Steatosis in chronic hepatitis C. Hepatology. 2007 Jan;45(1):80-7
15.
16.
17.
18.
Feng, W and
19.
20.
21.
1.
September,
2008. Comparing adaptive treatment strategies following sequential multiple
assignment randomization trials, Clinical and Translational Sciences
Research Institute, CHRC, RAND-Pittsburgh Institute, VA-CHERP.
2.
July, 2008.
Inference on dynamic treatment regimes following sequential multiple assignment
randomization trials, Center for Statistics at Queen Mary, University of
London.
3.
February, 2008. Adaptive treatment strategies – one
step forward towards individualized treatment rules. Dean’s Junior Faculty
Seminar Series, Graduate School of Public Health, Pittsburgh.
4.
February, 2008. Adaptive Designs in Clinical Trials.
5.
January 2008. Supremum weighted log-rank test and
sample size for comparing two-stage adaptive treatment strategies.
Department of Epidemiology, Biostatistics and Occupational Health,
6.
June 2007. Semi-parametric methods for estimating
causal effect of treatment strategies in two-stage randomization clinical
trials. ICSA 2007 Applied
statistics Symposium, Raleigh,
7.
May 2007. Weibull-based
approaches to survival analysis with applications to breast cancer data. Department
of Mathematical Sciences,
8.
February 2007. Comparing Adaptive Treatment Strategies:
Challenges and Solutions. Center for Health Equity, Research and Promotions
(CHERP), VA Health Care System,
9.
December 2006. Survival Analysis for Comparing Adaptive
Treatment Strategies. Department of Applied Statistics,
10.
April 2006. Survival Analysis in Two-stage
Randomization Designs in Leukemia Trials. Department of Mathematics and
Statistics,
11.
February 2006. Survival Analysis in Two-stage
Randomization Designs in Oncolgy Trials. Invited
presentation, Department of Biostatistics,
12.
March 2005. Survival Analysis in Two-stage
Randomization Designs. Invited lecture in the session CENSORED DATA IN THE
ENVIRONMENTAL, AGRICULTURAL AND MEDICAL SCIENCES. International Biometric
Society (ENAR) spring meetings, 2006, Tampa,
13.
March 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials. University of
14.
March 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials. Department of Biostatistics, and
Department of Statistics and Actuarial Science,
15.
March 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials. University of
16.
February 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials.
17.
February 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials. Department of Biostatistics,
18.
February 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials. Department of Health Studies,
19.
February 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials.
20.
January 2003. Survival Analysis in Two-Stage
Randomization Designs in Clinical Trials. Department of Mathematics and
Statistics,
21.
January 2003. Optimal Estimator of the Survival
Distribution and Related Quantities of Treatment Policies in Two-Stage
Randomization Designs in Clinical Trials. Department of Biostatistics and
Epidemiology,
1. Supremum Weighted Log-rank Test and Sample Size for Comparing Two-stage Adaptive Treatment Strategies, July 2008, International Biometric Conference, Dublin.
2.
Inverse-probability-weighting-based sample size formula
for comparing two-stage adaptive treatment strategies. ENAR Spring Meetings
2008,
3. Discussion on Two-Stage Treatment Strategies Based on Sequential Failure Times by Peter Thall (with Patricia Houck, and Jinhui Ko), ATSRG reading group meeting, November 2007, Department of Biostatistics, University of Pittsburgh Graduate School of Public Health.
4.
(poster) Weighted Kaplan-Meier Estimator for Adaptive
Treatment Strategies. SAMSI workshop on dynamic treatment regimes, June 2007,
Statistical and Applied Mathematical Sciences Institute, RTP,
5.
(poster) Weibull-based approaches to survival analysis: an
application to a breast cancer data set. 30th
6.
A supremum log-rank test for two-stage adaptive
treatment strategies and corresponding sample size formula, ENAR Spring
Meetings 2007,
7. Introduction to Adaptive Treatment Strategies with Examples (with Sachiko Miyahara). ATSRG reading group meeting, March 2007, Department of Biostatistics, University of Pittsburgh Graduate School of Public Health.
8.
Likelihood Inference for Survival Analysis in Two-stage
Randomization Designs, Joint Statistical Meetings, August 2006,
9. (poster) Inferences for Treatment Regimes in Two Stage Clinical Trials, Midwest Biopharmaceutical statistics workshop, May 2006, Muncie, Indiana.
10. (Poster) Insulin Resistance Is Independent Of Hepatic Steatosis and Is Augmented By Environmental Factors Such As Obesity in Patients With HCV Genotype 1 Infection, DDW, Chicago, Illinois, May 2005.
11.
Genetic variation in an interferon-stimulated gene, mxyovirus-1 (MxA), has a significant
protective effect from fibrosis in genotype-1 chronic hepatitis C virus
infection, DDW,
12.
A non-linear mixed effect model for hepatitis C viral
dynamics, International Biometric Society (ENAR) spring meetings, 2005,
13.
A non-linear mixed effect model for hepatitis C viral
dynamics, Joint Statistical Meetings 2004,
14.
Presented in the Faculty Seminar Series, Department of
Biostatistics,
15.
Race, Insulin Resistance, Visceral Adiposity and
Hepatic Steatosis in Genotype 1 Patients with Chronic
Hepatitis C, AASLD, November 2004
(poster).
16.
Efficient Estimation of the Survival Distribution for
Treatment Policies in Two-Stage Randomization Designs in Clinical Trials with
Censored Data. International Biometric
Society (ENAR) meeting 2004,
17.
Optimal Estimator of the Survival Distribution and
Related Quantities of Treatment Policies in Two-Stage Randomization Designs in
Clinical Trials. Joint Statistical
Meetings 2003, American Statistical Association,
18.
Optimal Estimator of the Survival Distribution and
Related Quantities of Treatment Policies in Two-Stage Randomization Designs in Clinical
Trials. International Biometric Society (ENAR) meeting 2003,
·
Shekhar Mehta
Graduated with an MS. Degree in Biostatistics (2006).
Thesis
title: Longitudinal
Analysis of Renal Function using ZIP GEE on OLT Transplant Patients Undergoing
NAC Prophylaxis
Current
position: Pharm.D program, University of Maryland
School of Pharmacy
·
Wentao Feng
Graduated with a Ph.D.in Biostatistics: April 2008.
Thesis
title: Inference,
Power and Sample Size Adaptive Treatment Strategies
Current
position: Sr. Biostatistician, Novartis
Pharmaceuticals Corporation
·
Sachiko Miyahara
Expected Ph.D. graduation date: August 2009.
Thesis
title: TBD
Current
position: TBD
·
Jinhui Ko
Expected Ph.D. graduation date: August 2009.
Thesis title: TBD
Current position: TBD
·Jesse Hsu
Expected Ph.D. graduation date: August 2010.
Thesis title: TBD
Current position: TBD
·Xinyu Tang
Expected Ph.D. graduation date: August 2010.
Thesis title: TBD
Current position: TBD