Right Questions, Questionable Answers

Alastair Wood in NEJM has some correct diagnoses for the ailing drug approval process. (Free full text on this one -- NEJM has started making some of their content of broad public interest accessible, but I'm gonna keep hammering on them until they open up the whole thing.) However, I'm not buying his prescription.

Presenting problems:

1. For most approved drugs, we don't have adequate long-term safety data. Sometimes we find out the hard way that widely prescribed drugs can be dangerous; no doubt many of them are and we don't even know it, because the data necessary to find that out aren't being collected.
   
2. Sometimes drugs are approved with the requirement that the manufacturers do so-called "Phase 4" studies, i.e. longer term follow-up on safety and/or effectiveness, but these requirements are weakly enforced, at best.
   
3. Many drugs haven't been tested head-to-head against others. To get approval, all you need is to beat placebo, or perhaps an alternative that's known to be sub-optimal. So we don't necessarily know which drug is really best.
   
4. Drug companies have a disincentive to develop drugs for long-term prevention, because it would take so long for them to get back their investment. For diseases associated with aging, such as Alzheimers and osteoarthritis, such drugs would be a great boon.
   
5. Drug companies have a strong incentive to concentrate on developing "me too" drugs -- slightly different versions of established drugs -- because there is little risk of hitting a dry hole, i.e. spending billions and never getting a commercial product. That steers investments away from true clinical breakthroughs, which are riskier to pursue. (He pays less attention to this, but they also invest in "evergreening" - slightly new formulations of their own drugs, and new combinations of old drugs, so they can keep exclusive marketing rights.)

Now, real clinical innovations are almost always based on publicly funded research, which the drug companies build on to develop commercial products. Obviously, we could just drive the public investment deeper toward clinically useful products, which would solve a lot of the problem. But Wood is dismissive of this idea, basically on the grounds that "it ain't gonna happen." (Smacks of creeping socialism and all that.)

As for safety, we could simply enforce existing requirements for Phase 4 studies, but Wood seems to assume that's asking too much. We could also develop improved surveillance and reporting systems for adverse events, and maybe piggyback some data collection on existing large-scale cohort studies to get better information. But Wood doesn't even consider these options. Similarly, we could just change the approval process to require head-to-head comparisons with existing standard treatments, or at least require more Phase 4 studies to do that, but again, it never seems to occur to Wood.

Nope. His solution to everything is to grant drug companies longer periods of marketing exclusivity if they will just do the right thing in each of these areas. That way, they can make more billions, just the motivation they need.

A significant problem with this idea, which Dr. Wood does not mention, is that it means the drugs will cost far more, for a longer period of time. Which means millions of people won't have access to them, the cost of health care will continue to rise, and inequalities will persist and widen. That would seem to be a downside.

So why does he focus exclusively on exclusive marketing rights and guaranteed return to investors, and ignore other solutions? Does this help to explain it?

Dr. Wood reports having received consulting or lecture fees during the past two years from Scirex, Sapphire Therapeutics, Abbott Laboratories, Elan Pharmaceuticals, NicOx, Medco, Novartis, and Eli Lilly; having acted as an adviser to various reinsurance companies regarding pharmaceutical matters; and serving as a director of Antigenics, chairman of the clinical advisory council and an investor in Symphony Capital, and a director of Symphony Neurodevelopment and Symphony Evolution. On September 1, 2006, Dr. Wood will become managing director of Symphony Capital. No other potential conflict of interest relevant to this article was reported.

Was there no-one else on the planet who could have written on this subject?

(Cross-posted from Stayin' Alive)