Are We Asking Enough of Our Clinical Trial Design?

The Long View of Drug Development and the Importance of Reimbursement

In the life cycle of a drug there are two major hurdles that pharmaceutical companies must cross: regulatory approval and reimbursement. A drug must be approved before someone pays for it, so the first step is regulatory approval, before it moves on to who’s paying and how much. Both are important processes with their own challenges and pitfalls.

Clinical trial data is common evidence used for both the regulatory approval and reimbursement. In designing a clinical trial, the focus has conventionally been on getting a drug past approval. In many cases, companies develop a regulatory strategy and allocate vast resources to get their drug past approval, only to find out that the market for the drug was not as great as they thought which can lead to unanticipated price cuts.

It’s long been our perspective that the goal line for drug development is not simply regulatory approval, but rather reimbursement. Incorporating reimbursement intelligence and sensibilities into clinical trial design requires recognizing this goal line and creating a dynamic process to achieve it.

We have been asked to speak on this topic a lot lately, first at the R&D Leadership Summit and then as part of a webinar featuring Oracle Health Sciences, Tufts Center for the Study of Drug Development, and Pharmaceutical Executive. We also recently wrote an article for pharmaphorum, "Overcoming the Market Access Hurdle through Better Planning of Clinical Trials." It’s safe to say this is a topic that is generating a lot of interest.

Clinical Trial Design: An Opportunity

A study designed to pass both hurdles will reduce the overall time and cost of the drug cycle. Companies willing to design trials to clear both hurdles would simultaneously save money and broaden their markets. Upon first assessment, this might seem to be a more difficult and costly approach, but it makes sense that one well-designed study, even if it costs more at the onset, will ultimately be more efficient and effective in bringing drugs to market.

In a recent poster presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), we looked at HIV drugs approved from 2000 to 2012, to see how often studies used in regulatory decisions were also used for reimbursement. The chart below shows that in this case, there were many of the same studies used by both regulatory and reimbursement agencies.

Not All Trials Measure the Same Outcomes

While both regulatory and reimbursement evaluations often work from the same clinical studies, the variability in endpoints across the clinical trials means that there is also variability in the outcomes that will be assessed for comparative effectiveness – making the choice of outcomes or endpoints even more important. The table below is for Phase III trials in Type 2 Diabetes and the frequency of different endpoints measured across four major classes of therapeutics. All endpoints can eventually become outcomes to be compared for reimbursement.

Going the Distance

Because reimbursement agencies and the regulatory agencies use the same studies, companies are offered an opportunity to kill two birds with one stone. However, the study must be designed to meet the overlapping, but distinct, needs of the two types of agencies. If studies aren’t designed with the long view of reimbursement, there may be trouble. A company may have to go back to work and do more studies in order to get someone to pay for a drug. In the early days of Context Matters, we used to illustrate our vision by saying “If no one pays for your drug, you don’t have a drug.” We presented the chart below at the recent webinar, “Transforming Clinical Development Strategy and Performance with Real-World Data” along Oracle Health SciencesTufts Center for the Study of Drug Development, and Pharmaceutical Executive.

It was one of the most surprising and resonant with the webinar audience and shows that trial design may affect as much as 66% of clinical reasons for negative decisions by Health Technology Agencies (HTAs), such as the UK’s NICE (National Institute for Health and Care Excellence).

Based on these numbers, how many of these “Do not recommends” from HTAs might have received a positive outcome if the initial trials had taken reimbursement into account?

Where We Go From Here

So what does all this mean and where do we go next? It’s our contention that clinical trial design affects more than clinical outcomes and that it is really the basis of market access strategy. The exciting part is that this message seems to be gaining traction.