More Accelerated Approval Changes Needed: Kaiser

Responding to an FDA draft guidance on the drug accelerated approval program, the Kaiser Permanente healthcare system says additional reforms are needed. The Kaiser response says accelerated approval shifts more evidence generation and evaluation to later in a product’s lifecycle, after its marketing has already begun. “The result of this shift has been that less robust evidence is required to satisfy FDA’s substantial evidence standard,” the letter says. It is the second public criticism of this FDA program this week.

Kaiser calls on FDA to work with Congress to statutorily require post-approval studies for all products approved through the accelerated approval pathway using surrogate endpoints and consider specific consequences for manufacturers who fail to complete them. In the interim, it says, the agency should create a publicly available record of successful surrogate and clinical endpoints and their corresponding clinical benefits by indication, with the evidence base underlying each of the measures.

Other points made in the system’s response are:

• a drug’s performance relative to a surrogate endpoint too often does not translate into clinical benefits for patients;
• a study found that most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within five years of the approval;
• among accelerated approval drugs converted to regular approval, only two-thirds showed improvement in overall survival or quality of life;
• FDA should examine how surrogate measures are determined “reasonably likely” to predict clinical benefit and should bolster access to a more comprehensive set of data that include all successful surrogate and clinical endpoints and their corresponding clinical benefits by indication with the evidence base underlying each of the measures;
• FDA should consider options for imposing consequences when postmarketing confirmatory trials are not completed on time, such as civil monetary penalties or greater clarity in labeling to indicate a mandatory postmarket trial has not been completed.

“The accelerated approval program’s current weaknesses deprive physicians, patients, and other stakeholders of vital evidence that can help improve outcomes and avoid paying for ineffective therapies,” Kaiser concludes. “Strengthening the accelerated approval program, in ways outlined above, and enacting legislation to statutorily require completion of postmarket trials or studies whenever sponsors rely on surrogate measures to support an approval, will ensure new, effective groundbreaking treatments reach patients quickly.”