The Evidence Base for Step Therapy for Pharmaceuticals

While step therapy has been around for a decade or more, it still represents one of the lowest hanging fruit for plan sponsors who want to improve the value received from their pharmacy benefit with minimal member disruption.  Today more than 50 therapy classes have the opportunity for step therapy, including several specialty medication classes.

When I recently returned to pharmaceutical policy work, I was surprised to see how few evaluations of step therapy had been conducted in the last decade, particularly considering step therapy’s high degree of popularity among plan sponsors in both private and public settings.  I was also surprised to see that most of the evaluations of step therapy that had actually examined clinical and economic outcomes were funded by pharmaceutical manufacturers rather than managed care organizations that can provide thought leadership on this benefit tool.

In a paper published today in the Journal of Managed Care Pharmacy , I review the literature on step therapy and highlight important areas for future research.  Clearly, evaluations of step therapy are needed for numerous therapy classes of clinical significance, such as statins and specialty medications.  This is important because one would fully expect patient response and the clinical implications of patient choices to vary by therapy class and by the underlying indication.  The lack of evaluations of step therapy in the Medicare Part D population is a particularly notable gap.

Most of the research to date has focused on the drug cost savings of step therapy, a necessary condition for step therapy’s uptake but certainly not the only outcome of interest.  While savings from step therapy are widely known within healthcare organizations, a better understanding the clinical profile of patients who receive prior authorization for brand medications or receive no medication following a step edit is an important area of inquiry as it has the potential to affect not only economic outcomes, but clinical outcomes and member satisfaction. Perhaps the second most notable gap is the lack of evaluation of alternative forms that are growing in popularity, such as removal of grandfathering and integration of medical claims into the real-time step edits.

 In the paper, I also discuss some of the key methodological concerns with the publications to date and highlight examples of potential bias.  Based on this review, here are a few methodological tactics you should watch for when considering step therapy evaluations:

• Reporting of non-significant findings as if they were statistically significant
• Evaluation of all-cause medical expenses rather than disease-related expenses (all-cause medical costs are highly variable are have a greater chance of showing random differences across groups for reasons that have nothing to do with the program being evaluated)
• Inclusion of patients who were unaffected by the program to calculate drug savings, which will reduce the magnitude of apparent savings
• Examination of a small subpopulation of patients affected with extrapolations to the entire program

 As I point out in the paper, the popularity of step therapy among commercial, Medicaid, and Medicare plans is no doubt due to the wide availability of generic alternatives that offer significant savings, the strong clinical evidence that typically underlies these programs, and their ability to affect only new users, thereby minimizing member disruption. It is important that evaluations of step therapy keep pace with their growing use in order to optimize program design and patient outcomes.

Are Statins Cost-Effective for Primary Prevention?

There has been no shortage of headlines about the cost-effectiveness of statins in recent weeks, and another study was reported today in Journal of the American College of Cardiology. In a pharmacoeconomic model developed by Choudry and other researchers at Brigham and Women’s Hospital/Harvard Medical School using the JUPITER (Justification for the Use of statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial, the authors project that the average JUPITER patient treated with rosuvastastin will have $7,900 higher life costs and an additional 0.31 quality-adjusted life years (QALYs), providing a cost-effectiveness ratio of $25,000/QALY. Against the widely used benchmark of $50,000/QALY, the authors conclude that statins appear to be cost-effective for primary prevention.

These results are somewhat contradictory to the recent Cochrane Collaboration review of statins in primary prevention, which recommended that statins be prescribed with caution to those at low risk of cardiovascular disease. The researchers reviewed data from 14 trials and nearly 35,000 patients. Although clinical benefits were found, the authors concluded that “ there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life.” The authors pointed out that all but one of the trials they reviewed were industry-sponsored and that you cannot simply extrapolate results from studies of people with history of heart disease to those without.

So why the differing conclusions about statin cost-effectiveness? In a commentary accompanying the latest study, Mark Hlatky, a physician and researcher at Stanford, provides some insights on the study. Hlatky points out that the model was only based on JUPITER and not the full breadth of evidence, which has NOT found large reductions in risk from the use of statins in primary prevention. Furthermore, the longer term risk reduction is simply unknown because clinical trials rarely last longer than 5 years. Choudhry assumed that rosuvastatin would reduce the risk of cardiac events by more than 50% for 15 years. If the same effect does not extend beyond 5 years, the cost-effectiveness grows to $62,100/QALY. The assumption of proportional risk reductions across levels of severity has been a limitation of many of the more recent cost-effectiveness analyses of statins.

There are additional questions about this and other recent studies of statins for primary prevention. Choudhry did not have data on long-term adverse effects, to which their model was quite sensitive. As Hlatky pointed out, if patients taking rosuvastatin had a 2% decrease in their well-being, the cost-effectiveness ratio grew to more than $62,000 per QALY. Also unclear is whether the model adjusted for medication persistency rates over the longer-term. Studies have shown that even after the first year of therapy, 50% of patients discontinue their statin medication, leading to increased short-term costs with little or no clinical benefit.

In hearing this latest information, many providers and plan sponsors are likely to point to diet and exercise changes as the solution to reducing the long-term risk of cardiovascular disease. Unfortunately, a recent Cochrane Collaboration review also found that education and counseling to encourage people to change their diets and stop smoking had little or no impact on deaths or disease caused by cardiovascular disease. An accompanying editorial pointed out that “Although various multiple prevention strategies exist, the most effective and cost-effective intervention for primary prevention in adults at low risk currently remains unclear.”

Do you know what percent of your current statin use is for primary prevention? Depending on the population, it could be as high as 50% of your statin users and may be growing.  If you are funding a wellness program to reduce the risk of cardiovascular disease, do you have any rigorous evidence that the program is leading to sustained changes in behavior?