Thank you for the opportunity to speak today. My name is Dr. Stephanie Fox-Rawlings. I am a Senior Fellow at the National Center for Health Research. Our research center analyzes scientific and medical data to provide objective health information to patients, providers and policy makers. We do not accept funding from drug or device companies so I have no conflicts of interest.
Sickle cell disease and the crises that it causes are a serious problem. Patients deserve and need new treatments. This requires high-quality clinical studies to demonstrate whether new treatments are effective and safe. When many of the patients that start a study drop out before it is completed, it is impossible to accurately evaluate the benefits compared to the risks.
The sponsors used a good clinical design: it was randomized, double-blind, placebo-controlled and multicenter. However, because the difference in the number of sickle cell crises between drug and placebo arms was modest. This could still be a meaningful improvement for at least some patients, but the disproportionate dropout rate makes it difficult to be confident of whether the drug is effective.
The briefing documents from the company and FDA did not discuss the methods that the sponsor used for patient retention. There are many reasons why patients drop out of studies, but it usually comes down to one issue: the incentives don’t outweigh the disincentives for patients to participate. Disincentives can be adverse events, or they can be lack of benefit, or they can be logistical – maybe participation is too time consuming, requires going somewhere that is inconveniently located, or perhaps the participants need childcare for children in the family. Often, participation may be expensive if it requires arranging transportation, paying for parking, paying for childcare, or taking time off from work. To make a study successful, sponsors need to make it easy for patients to participate and have incentives – often financial — to encourage participation. Since most of the dropouts were not due to adverse events, incentives or other methods may have retained more patients, which would have strengthened the data and made the study easier to evaluate.
FDA should approve new treatments based on clearly demonstrated evidence of efficacy and safety. This requires high-quality clinical trials where post patients stay in the trial. FDA should not approve a drug with questionable benefit when the dropout rate is concerning.