The Blame Game

There's been a lot of finger wagging lately as to who's to blame for the undeniable decline in new drug approvals.

On one side you have CEOs of leading pharmaceutical companies becoming more vocal in the press about the FDA's more conservative approach since Vioxx (including Schering-Plough, Wyeth and Novartis), and on the other, you have the FDA raising the mirror to the industry's face, attributing the slowdown to a slump in quality research, in turn leading to a lower number of submissions for new drug applications. The Motley Fool posted looks from both perspectives just last week ( Lawler vs. Orelli).

Amidst the finger-wagging, one fact remains constant: corporate R&D spending has shot up 150 percent during the past decade. So the real question is, where's that money going - and why?

Walter Armstrong hits on what is likely a big part of the answer in a recent article in Pharmaceutical Executive, where he highlights the problem of the FDA's use of approvable letters, a type of FDA missive he aptly describes as being an "odd regulatory response that isn't quite an approval and isn't quite a rejection." The letters, he argues, have become "a major part of the FDA's arsenal for dealing with (or, as many might say, not dealing with) new drug applications (NDAs)."

Approvable letters ask drug companies to conduct more studies to collect additional data on drugs under consideration for FDA approval. These requests add up dollar-wise, and, even more important, hamper the speed at which new drugs are brought to market. The real problem would be if the cost-benefit ratio of responding to the FDA's requests becomes so high that, in addition to clogging up product pipelines, the investor dollars that filled them in the first place ran dry compromising future pharmaceutical innovation.

Even former Intel CEO Andy Grove jumped into the blame game recently when, in an interview with Newsweek.com, he criticized the pharmaceutical industry as being plagued by a stagnant culture of innovation.

He noted that "if a clinical trial doesn't work - which means the average of all the patient responses is not better than the average of a placebo treatment - they just throw [the drug] away, when in fact the averages may hide stuff that did work, and something that made patients different [such as genetics]. I've never heard anyone talk about the opportunity costs of a good drug being thrown away. But a good drug wrongfully convicted means the loss of benefits goes on forever."

Mr. Grove makes a noteworthy point here, and I share his concerns. I've argued elsewhere that even though the FDA assumes that no useful conclusions can be drawn from analyzing subsets of data from drug trials, such analyses can, in fact, when done intelligently and with great care, provide much useful information - and uncover some of the good "hidden stuff" that Grove is worried we might be missing.

Clinical trial experts Kent and Hayward wrote to similar effects in JAMA last month (need subscription) that "the results of clinical trials might not apply in a straightforward way to individual patients, even those within the trial." Statistical analyses currently widely used in clinical research only describe average effects of a treatment and fail to address the needs of the entire distribution of patients. Even though on average there is a benefit, some patients may benefit and some may be harmed by a therapy.

The FDA is letting potential benefits fall by the wayside by using outdated rigid statistical approaches and refusing to allow subset analyses to be factored into its decisions on new drug approvals, and this is indeed inhibiting pharmaceutical industry innovation - contributing to a drop-off in important new drugs being brought to market and made available to the patients who need them.

Comments

[realitytrumpsbull]

Does this mean they'll finally legalize marijuana, or would that put too many people
out of work? LOL