Analysis Group affiliate Robert Navarro, PharmD, is Clinical Professor in the Department of Pharmaceutical Outcomes & Policy, University of Florida, College of Pharmacy, as well as a cofounder and the first president of the Academy of Managed Care Pharmacy (AMCP) and the Foundation for Managed Care Pharmacy (FMCP). In this Q&A moderated by Analysis Group Manager Darya Rose, Professor Navarro discusses the real-world effectiveness “evidence gap” at the time of regulatory approval and how pharmaceutical manufacturers can leverage post-marketing studies to support a product’s value proposition to payers.
Ms. Rose: What role does post-marketing real-world evidence play in supporting a drug’s value proposition to health plans?
Analysis Group Affiliate Robert Navarro
Professor Navarro: Health plan decision-makers have asked for real-world, active-comparator trials for decades, but these results are rarely available at the time of regulatory approval. Most of the time drugs are launched on the basis of randomized placebo-controlled trials that provide evidence on efficacy and safety, but do not demonstrate real-world effectiveness, which is an evidence gap. The "controlled" nature of pivotal clinical trials requires specific inclusion and exclusion criteria as well as a high level of adherence. Furthermore, patients in real-world clinical practice rarely have a single medical condition; rather, they suffer from multiple comorbidities and use multiple medications, which may lead to drug-drug interactions and suboptimal utilization, further exacerbating the gap between efficacy and effectiveness.
Ms. Rose: In what context is real-world data considered and reviewed by payers?
Professor Navarro: Health plans will make coverage decisions with the data that is available at any given time, and typically they make assumptions based on previous experience in the absence of additional evidence. A question that health plans always have is, "Which patients are the appropriate candidates for this drug?" Without real-world evidence of effectiveness, plans use prescribing information and eligibility criteria from the clinical trial program to develop prior authorization criteria. Data from observational or pragmatic trials can provide additional information to refine prior authorization or re-authorization criteria and demonstrate real-world value of the product to payers. This evidence may also lead to better patient management and outcomes, as well as more informed use of medical resources.
After a drug has been in the market, health plan decision-makers typically use real-world retrospective claims analyses and comparative trials or meta-analyses in an attempt to answer questions about drug effectiveness. Therefore, data from real-world studies is combined with findings from randomized controlled trials for a complete efficacy and effectiveness profile on a drug relative to competitors. Today, health plan decision-makers review their own internal drug utilization files (administrative claims data) in an attempt to construct estimates of drug effectiveness in their own member populations. Published real-world data is used to confirm or supplement their own experiences and internal investigations.
Ms. Rose: What types of real-world studies should manufacturers consider to supplement clinical trial data typically available at the time of product launch?
Professor Navarro: Large retrospective databases can be helpful in identifying drug use, costs, and outcomes for representative plan populations, although claims data is limited in its ability to inform definitive conclusions. Prospective pragmatic or observational trials are often more useful because they generally have richer data sets, specify inclusion and exclusion criteria and a limited range of treatment options, and include claims or encounter data in addition to data derived from health records. Both types of studies can be informative, but a well-designed prospective uncontrolled or semi-controlled trial may be more influential from a payer perspective.
It is never too early to start designing a real-world data collection program, and I suggest starting the planning process before a Phase 3 pivotal trial has begun. Nevertheless, a manufacturer should incorporate emerging evidence on the drug and on the competitive landscape into the study protocol over time to reflect the most up-to-date understanding at the time of product launch. The study methodology, endpoints, and analyses should be designed with the payer perspective in mind, to ensure that the results will provide informative and actionable evidence of the product’s value to health plans. Payers are likely to disregard evidence from studies that they perceive as not applicable to their member populations, so it can be very useful to confirm the study design with them before embarking on a real-world data collection program. Gathering payer insight early on in the process helps to ensure that the study output will ultimately lead to a better understanding of the product’s real-world effectiveness and improve market access. ■