Post-approval trials of new drugs are showing limited clinical value

Pharmaceutical CommercePharmaceutical Commerce - September/October 2017

Is the accelerated-approval process providing a net benefit to patients?

It's a classic case of asking whether the glass is half-full or half-empty: of 22 oncology drugs, for 24 indications, granted accelerated approval between 2009 and 2013, and with at least three years of follow-on study completion, post-approval requirements were completed for 10 of the 24 indications and demonstrated efficacy. Of the 14 indications not yet completed, there were delays, failed results or terminations; seven of the 14 were still progressing. And of those 14 indications, clinical benefit had not yet been confirmed for eight indications that had been approved five or more years earlier.

Furthermore, "most" of the postapproval trials that showed clinical benefit relied on surrogate measures rather than clinical outcomes, the authors note, indicating that the same limitations of the pre-approval trials (not using blinding, randomization or comparator grups) exist in the post-approval trials.

That's the summation of a paper published in the current issue of J. of the American Medical Assn. An accompanying guest editorial by Robert Califf of Duke Univ. School of Medicine asked whether the data raises "concerns about whether the US regulatory system has become too permissive by not requiring traditional randomized controlled trials" for postmarketing evaluations. He also notes that "because of the complexity of diseases and therapies, the vast majority of biomarkers are not good surrogates for improved patient outcomes."

To patient advocates and others seeking quicker access to investigational drugs, the results say that there's a better system in place; to industry critics, the results say that FDA is bending the rules around gold-standard, scientifically sound clinical research. The mixed message probably isn't going to slow down the trend toward faster approvals, sought by, among others, the new FDA Commissioner Scott Gottlieb; but it will create challenges for healthcare providers making life-and-death decisions about therapies. For the pharma industry, the opportunity for faster market access will be balanced against the risk of a highly publicized drug introduction suddenly going south.

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