PCORI RESPONSE
I have read the comprehensive analysis concerning plans and standards for
methods to perform Patient Oriented Outcomes Research. The document, which is
longed and detailed, reflects a great deal of thought and effort.
However, it is striking by its limited inclusion of a creative vision for the future,
and its total disregard of our group’s ground breaking advances in outcomes research
over the past decade.
More than 10 years ago we speculated that a large Electronic Health Record
Database could potentially transform the performance of outcomes, including
comparative effectiveness, research. This would require the confluence of 2 major
developments.
1. A well designed Database that: (1) reflected the overall population, (2) was
sufficiently large and (3) contained all the relevant health information.
2. Development of analytic methods that could overcome “unmeasured
confounding” and/or bias and thereby produce valid results (or at least the
capacity to determine whether or not the results were valid).
A sufficiently large database that can be analyzed in a fashion that yields reliable
results could transform OUTCOMES RESEARCH by providing the capacity to
investigate patients with virtually any subset of features.
We used a model EHR Database (the UK GPRD) which appeared to meet most of
the important features to rigorously determine whether reliable outcomes research could
be accomplished. These studies provided evidence that reliable outcomes research could
be performed, but only if analytic methods that could overcome “unmeasured
confounding” were utilized. We developed one such method (Prior Event Rate Ratio
adjustment) that works effectively. While the PERR method will not be able to be
utilized for every type of outcomes study, it demonstrates that it is possible to develop
analytic methods that can address this Critical Issue.
The focus on PCORI should be on the development in the US of a large (greater
than 50 Million patient) database that reflects the overall population, proof that the
database can yield reliable answers to outcome research questions (along the lines we
have shown with the GPRD database), and finally the development of additional methods
that can reliably overcome the problem of “unmeasured confounding”.
If this is accomplished cost effective, evidence based healthcare that is patient
focused can be achieved. This is everyone’s goal, but it will not happen unless the
missions of PCORI, AHRQ and other entities are laser focused on achieving this goal and
recognize that new database and analytic methods are needed.
The publications of our work that have led to my views about the future are
enclosed. To my knowledge none of them were quoted or given consideration in the
current version of the PCORI document.
It is time for someone to wake up and recognize the potential far reaching
implications of these studies.
Sincerely,
Richard L. Tannen, MD
Professor of Medicine
University of Pennsylvania Perelman School of Medicine
PUBLICATIONS
1. Tannen, RL, Weiner, MG, Marcus, SM. Simulation of the Syst-Eur randomized
control trial using a primary care electronic medical record was feasible. Journal
of Clinical Epidemiology 2006, 59:254-264.
2. Tannen RL, Weiner MG, Xie D, Barnhart K. Simulation of the women’s health
initiative trial using data from a primary care practice database. Journal of
Clinical Epidemiology 2007, 60: 686-695.
3. Tannen RL, Weiner MG, Xie D, Barnhart K. Estrogen affects post-menopausal
women differently than estrogen plus progestin therapy. Human Reproduction
2007, 22: 1769-1777.
4. Weiner MG, Barnhart K, Xie D, Tannen RL. Hormone replacement therapy and
coronary heart disease in young women. Menopause 2008, 15: 86-93.
5. Weiner MG, Xie D, Tannen RL. Replication of the Scandinavian Simvastatin
Survival Study using a primary care medical record database prompted
exploration of a new method to address unmeasured confounding.
Pharmacoepidemiology and Drug Safety 2008, 17: 661-670.
6. Tannen RL, Weiner MG, Xie D. Replicated studies of two randomized trials of
angiotensin converting enzyme inhibitors: Further empiric validation of the
“prior event rate ratio” to adjust for unmeasured confounding by indication.
Pharmacoepidemiology and Drug Safety 2008, 17: 671-685.
7. Tannen RL, Weiner MG, Xie D, Barnhart K, Perspectives on hormone
replacement therapy: the Women’s Health Initiative and new observational
studies sampling the overall population. Fertility & Sterility 2008, 90: 258-264.
8. Tannen RL, Weiner MG, Xie D. Use of primary care electronic medical record
database in drug efficacy research on cardiovascular outcomes: comparison of
database and randomized controlled trial findings. BMJ 2009, 338; b81
[doi:10.1136/bmj.b81]
9. Yu M, Xie D, Wang X, Weiner MG, Tannen RL. Prior event rate ratio
adjustment: numerical studies of a statistical method to address unrecognized
confounding in observational studies. Pharmacoepidemiology and Drug Safety
2012, 21(S2): 60–68.
10. Tannen RL, Xie D, Wang X, Yu M, Weiner MG. A New “Comparative
Effectiveness” Assessment Strategy using the THIN Database: Comparison of
the Cardiac Complications of Pioglitazone and Rosiglitazone. [Submitted for
publication]