Payers and clinical key opinion leaders in the United States, Europe and Canada feel that biopharmaceutical companies consistently fail to deliver evidence of value and that clinical trial designs should have a greater focus on payer, physician and patient needs. Perhaps we shouldn’t be surprised, as U.S. payers have managed to force net price declines over the last two years and an annual survey shows that return on investment on pharmaceutical research and development for new FDA approved drugs steadily declined to only 1.8% in 2019. Is pharma’s current dialogue about value no more than lip service?
We recently surveyed North American and European payers about the quality of evidence in biopharma launch dossiers. Around half of the respondents weren’t satisfied with the evidence dossiers and raised concerns primarily around choice of comparators, endpoint selection and inclusion criteria in the trials. In fact, as one German KOL told us, “Drugs are about patients and doctors and not about the regulatory agencies.” Offering stronger evidence of value may result in higher cost or risk of clinical failure, however, we feel that it’s important to ensure that these options are expressly included in the decision-making process.
Here are some of the most important, high-level takeaways from our survey:
- Our survey found that 83% of payers are unhappy with the choice or trial comparators. Payers and KOLs don’t like single-arm trials and generally see little value in placebo-controlled trials. They argue for a randomized comparative trial versus the standard of care. As one German payer told us, “Still we see single arm trials...strange.”
- Nearly two-thirds (60%) of respondents, across both geographies, challenge the relevance of endpoints selected in current evidence dossiers. The main concern with endpoints is the selection of surrogate endpoints, especially in oncology, where response rates are used in place of overall survival or progression-free survival. As one German KOL shared, there are “too many surrogate endpoints, hard clinical endpoints are better for sure.”
- In terms of trial population, payers and KOLs have slightly divergent perspectives. Payers feel more comfortable with focused homogenous populations in clinical trials with a clear demonstration of clinical improvement over a comparator for a typical patient. On the other hand, KOLs would like trial populations to reflect the “real world” with more heterogeneity so they’re able to make informed prescribing decisions. A U.S. payer told us, “I’m OK with narrow trial groups but would expect to narrow the access to the population under that form of review.”
Some of these payer requests may seem like asks for perfect evidence. However, we need to challenge whether we’re sufficiently considering the downside of not providing stronger evidence of value and the upside of addressing the need through better and more rapid market endorsement of our drugs. The FDA isn’t the drug buyer! Situations between drugs may be different as well. In rare and orphan indications, for example, it’s not possible to do a double-arm study with standard of care as a comparator, but payers understand that. At the same time, it’s important to discuss the nuanced “what-ifs” with the stakeholders to identify how to clearly highlight the asset’s value in the evidence dossier. A clinical development process shouldn’t be limited to checking a box to ask for payer and KOL input on evidence design, but rather taking a closer look at stakeholder requests and considering their inclusion in the design.
Many R&D organizations strongly favor the “quick to FDA approval” option, which is increasingly likely to constitute a “race to nowhere.” While speed of approval is important, we may need to listen more to our customers and ensure that we have compelling evidence that leads us successfully beyond FDA and EMA approval, but also ensures rapid uptake and broad utilization.