Earlier this year we wrote about the challenges of attaining market access after regulatory approval, and the need to design clinical trials with both regulatory agencies and market access in mind. In order to gain market access, drugs not only have to pass the regulatory hurdle, but in most countries they also have to pass the reimbursement / Health Technology Assessment (HTA) hurdle. So for a drug manufacturer, the goals of clinical trials have expanded; a drug not only has to show efficacy and safety to the regulatory agencies, it must also demonstrate comparative efficacy to reimbursement agencies. The pressure on manufacturers to get the clinical trials “right” has now doubled.
We recently presented research at the 17th Annual International Society for Pharmacoeconomics and Outcomes Research (ISPOR) European Congress that evaluates whether clinical trial design matters to HTA agencies. That is, how can clinical trial design help or hinder manufacturers’ chances at reimbursement?
Evaluating the Importance of Trial Design
HTA agencies base their reimbursement decisions on assessments of clinical and (for some agencies) economic data. Our analysis focuses on the clinical assessments and reimbursement decisions of 1,702 HTAs from six agencies: the Canadian Agency for Drugs and Technologies in Health (CADTH), Germany's Gemeinsamer Bundesausschuss (GBA), France's Haute Autorité de Santé (HAS), England's National Institute for Health and Care Excellence (NICE), Australia's Pharmaceutical Benefits Advisory Committee (PBAC), and the Scottish Medicines Consortium (SMC). We categorized their decisions as “positive” or “negative.”
We made note of all reviews that described clinical trial defects. We categorized them as “explicit trial design defects” and “potential trial design defects.” Reviews with explicit trial design defects were those that specifically noted the use of inappropriate comparators or inappropriate patient populations. Reviews with potential trial design defects cited lower, uncertain, or unknown efficacy, insufficient evidence, or lack of evidence.
We found a strong link between explicit or potential trial designs and negative reimbursement decisions. Reviews that cite explicit trial defects result in positive decisions only 13% of the time. This pattern held true for each individual agency examined.
In breaking down the data, we found that:
- G-BA was the agency most likely to cite an explicit trial defect (38% of the time), while HAS and SMC were the least likely (1% of the time)
- Among disease conditions with more than 10 reviews, explicitly cited trial defects were mostly frequently seen in Cystic Fibrosis and Parkinson’s Disease (18% and 17%, respectively)
- Reviews that cite potential trial defects fare little better and result in positive reimbursement decisions 23% of the time. This also held true for each agency. Again, G-BA was most likely to note a potential trial defect in reviews (46%) while SMC was least likely (8%). Potential trial defects were most frequently cited in Atrial Fibrillation and Depression reviews (50% and 50% respectively)
Trial Design Matters
Based on the above data, we see that trial design can be a very important factor in determining the success or failure of a drug to attain market access. HTA and regulatory agencies often value different comparators and patient populations. To ensure success with regulatory agencies and with HTA reimbursement, it is important to look at the whole picture, and to do so early.
The question then becomes are HTA considerations included in trial design and if not, why?