A recently published study by Dyer O has exposed major drawbacks in the fast tracking process of some drugs available to the American patients without any stringent clinical evidence of their benefits. Drugs that receive accelerated approvals from the US Food and Drug Administration (FDA) often rest on a flawed evidence base, says research that evaluated over 7000 clinical studies conducted with over 37 drugs that were given such approvals between 2000 and 2013. Researchers from the London School of Economics and Political Science (LSE) and the United States say that many US patients with serious illnesses are being treated by drugs which have questionable data.

Drugs for which the accelerated approval is applied are assessed for their ability to provide clinical benefits but the bar for their market entry is far lower than those receiving regular approval. The potentially capable drugs can receive marketing authorization on the basis of surrogate measures that are easy to obtain, rather than clinically meaningful outcomes, with the help of FDA’s accelerated approval process. The aforementioned study is the first in the world to systematically evaluate more than 7000 clinical studies conducted on drugs receiving accelerated approval by the FDA; and the shortcomings were due to the FDA introducing more flexibility to its evidence standards over the past three decades. The evidence ultimately accrued on the drugs getting ‘accelerated approval’ has major flaws and is inadequate to address the information needs of patients and doctors, and other decision makers in healthcare systems.

The key findings of this study include:

  • Randomized trials, the gold standard of evaluating clinical effectiveness, constituted only a small minority of existing evidence;
  • The FDA approval did not approve of the therapeutic areas in about one-third of randomized trials; also, out of these, less than half evaluated the therapeutic benefit of these drugs but used them instead as common backbone treatments;
  • Drugs that receive accelerated approval were often tested simultaneously in different therapeutic areas;
  • Most drugs did not show substantial time lag apparent between the average start date of trials evaluating their effectiveness and their use as background therapy;

However, on a flip side, some people in the industry believe that this is not news. Moreover; post-marketing studies are performed in only two-thirds of cases and when performed, it is with the median delay of 4 years. Accelerated approval is associated with unreasonable delays in market withdrawal, even in the case of drug-related deaths. For lack of efficacy, the process is even slower; for instance, drotrecogin alpha was not withdrawn for 10 years after initial approval and bevacizumab was approved for metastatic breast cancer in February 2008 under the FDA accelerated program and the license was not revoked until November 2011. No one can understand how the system can have been so wrong for so long. FDA as well as the European Agency (EU) goes too fast for approval and too slow for withdrawal.

Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and non-randomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including such drugs wanting accelerated approval are not designed to directly evaluate their clinical benefits but to incorporate them as standard treatment.

About MarksMan Healthcare

MarksMan Healthcare Solutions (ISO 27001:2013) is an International knowledge-based Patient Access Services (PAS) and Medical Communications consulting firm based in India. It specialises in HEOR, PRMA and RWE solutions.

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