'Bench to Behavior': Translating Comparative Effectiveness

Translating The Results By Jerry Avorn and Michael Fischer doi: 10.1377/hlthaff.2010.0696 HEALTH AFFAIRS 29, ‘ ’ NO. 10 (2010): 1891–1900 Bench To Behavior : ©2010 Project HOPE— The People-to-People Health Translating Comparative Foundation, Inc. Effectiveness Research Into Improved Clinical Practice Jerry Avorn (javorn@medsoc ABSTRACT The new national emphasis on comparative effectiveness .harvard.edu), an internist and research is likely to generate an unprecedented volume of new findings. drug epidemiologist, is a professor of medicine at It is essential to anticipate the obstacles that front-line health care Harvard Medical School and chief of the Division of professionals will face in translating these results into better clinical Pharmacoepidemiology and decision making. We review the current barriers to the dissemination of Pharmacoeconomics, Department of Medicine, at evidence-based clinical recommendations, including problems with Brigham and Women’s continuing medical education, provider incentives, and quality assurance. Hospital, in Boston, Massachusetts. We then propose solutions, including more effective educational outreach programs, requirements for practitioners to master important findings, Michael Fischer is a health services researcher and and alignment of incentives to encourage evidence-based practice. Such primary care physician in the strategies can lead to policies that could encourage the uptake of new Division of Pharmaco- epidemiology and Pharmaco- comparative effectiveness data and encourage their translation into better economics, Department of clinical practice. Medicine, at Brigham and Women’sHospital.Healsois an assistant professor of medicine at Harvard Medical School. he industrialized world has focused funding, and the creation of the new Patient- intensely in recent decades on ap- Centered Outcomes Research Institute, the plying advances in basic biomedical United States is now gearing up to produce an research to the production of new unprecedented volume of new research evaluat- drugs and devices. However, this ing comparable therapeutic interventions. It is T“bench to bedside” translation has not been critical to understand the barriers that exist be- matched by comparable attention to using that tween generating these comparative effective- research to change what physicians actually do— ness findings and changing practice by front-line what might be called the “bench to behavior” physicians and other health professionals—and translation. A major gap persists between the to develop strategies to overcome these ob- best available information on therapeutic effec- stacles.3 tiveness and safety, on the one hand, and typical Delaying the adoption of research findings— patterns of care, on the other.1,2 Problems in or refusing to adopt them—is not a novel prob- translating into practice the conclusions of sev- lem in medicine. In the mid-nineteenth century, eral major comparative effectiveness research Ignác Semmelweis in Europe and Oliver Wendell trials, as discussed below, show that studies Holmes Sr. in the United States employed obser- may be rigorously designed and carried out, pro- vational and then interventional “comparative ducing important clinical findings, yet remain effectiveness” studies to demonstrate that hand poorly applied in typical practice settings. washing by health professionals before they de- livered babies was associated with a marked re- duction in maternal death from puerperal fever, Emergence Of New Research a serious bacterial infection that can affect moth- Findings ers after childbirth. Yet it took the medical pro- As a result of recent changes in federal law, new fession years to incorporate these life-saving October 2010 29:10 Health Affairs 1891 Downloaded from HealthAffairs.org on August 21, 2018. Copyright Project HOPE—The People-to-People Health Foundation, Inc. For personal use only. All rights reserved. Reuse permissions at HealthAffairs.org. Translating The Results insights into standard practice.4 was given to patients, there was no apparent In 1992, Elliott M. Antman and colleagues indication that its use was necessary.6 demonstrated the long lag between document- Below we review the barriers to the implemen- ing effective advances in heart disease care and tation of insights from comparative effectiveness incorporating those findings into expert review research in routine clinical practice.We also pro- articles and textbook chapters. In addition to pose ways of overcoming the barriers to help documenting the translation-to-practice prob- move comparative research findings from the lem clearly, they also pointed out that clinical pages of medical journals into typical patient experts themselves often contributed to delays care settings. in the inclusion of important new findings into standard texts and reviews.5 Antman and colleagues suspected that even experts struggled Causes Of The Problem to find and evaluate all of the new evidence in No Effective Dissemination The evolution of a given clinical area. the clinical trial has focused attention on a num- The nature of the problem has not changed. ber of its critical components. These include rig- With increasingly powerful and costly treat- orous calculation of the necessary sample size ments coming onto the market, and with the and the need for human subjects protection, expected avalanche of new comparative effective safety monitoring boards, and accurate and ap- research, we need to overcome these long-stand- propriate statistical analysis.7 Despite these im- ing barriers to translating results into practice, portant advances, most clinical trial designs do to make certain that these new insights are ap- not yet include a plan for getting the study’s plied appropriately. findings translated into the world of patient care. Research results can also have unintended ad- verse consequences if they are misapplied. An Flawed Underlying Assumptions example is the Randomized Spironolactone Many biomedical researchers assume that as Evaluation Study (RALES), which demonstrated soon as new information that can improve the the advantage of adding spironolactone (a quality or cost-effectiveness of care is published diuretic) to the drug regimens of patients with in the medical literature, it will be noticed and severe heart failure.8 However, use of spirono- promptly adopted by clinicians and policy mak- lactone in patients older and frailer than those ers. This could be called the “If you discover it, included in the clinical trial produced a strik- they will come” philosophy. Although enormous ingly higher rate of dangerous side effects.9 effort and expense are devoted to conceiving and The problem of underapplication of research implementing a carefully wrought clinical trial, findings dogged a project funded by the National there is often no plan for putting its results into Institutes of Health, the Antihypertensive and practice once it is finished. Lipid-Lowering Treatment to Prevent Heart At- It is difficult to think of an example of a major tack Trial. Known as ALLHAT, this was a land- biomedical discovery in which this passive pos- mark comparative effectiveness study of more ture alone has been followed by adequate prac- than 40,000 patients with hypertension, in tice change. Vaccination against polio, the which subjects were randomly assigned to four concept that mild-to-moderate hypertension re- drug regimens. quires treatment, the use of statins to prevent Contrary to the expectations of many experts, cardiovascular events, the administration of the trial demonstrated that older thiazide-type antibiotics near the time of surgery—all are in- diuretic drugs, available in generic versions, terventions for which having clear evidence were as effective as or better than three other in the medical literature was not adequate in heavily marketed competing regimens.10 This itself to consistently transform practice on a created an opportunity for substantial improve- large scale. ment in the treatment of hypertension, with bet- A laissez-faire approach to adopting effective ter care at lower cost.11 care improvements can result in both under- and However, publication of the ALLHAT hyper- overuse of the studied intervention. One exam- tension findings had only a brief, modest effect ple is the enormous investment in multiple on prescribing.12 The reasons included the initial studies of the comparative effectiveness of anti- absence of a dissemination plan for the findings; platelet regimens with and without clopidogrel effective countermarketing by the manufac- (Plavix) to reduce the risk of cardiovascular turers of the threatened products; and criticism events. Despite this investment, Niteesh of the study—some of it justified—by several hy- Choudhry and colleagues recently found that pertension experts.13 An important next step was in almost half of the cases in one large, state- taken when the National Heart, Lung, and Blood funded program in which this costly medication Institute funded an implementation and dis- 1892 Health Affairs October 2010 29:10 Downloaded from HealthAffairs.org on August 21, 2018. Copyright Project HOPE—The People-to-People Health Foundation, Inc. For personal use only. All rights reserved. Reuse permissions at HealthAffairs.org. semination program to encourage incorporation research does not favor it. of the landmark study’s results into practice.14 Official Marketing Programs Sometimes, a Unfortunately, the program’s impact was small, new drug or device will be found

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