A new report from Congress’s Government Accountability Office — am I the only one who didn’t notice that it changed its name from "General Accounting Office" over two years ago? — attempts to determine why the number of actual applications for approval of new drugs has increased at a much slower rate than the increase in pharmaceutical industry research and development expenditures.

Per the GAO panelists, "conflicting pressures of avoiding risk and producing a high return on investment" combine to curtail the development of the most innovative new drugs:

[C]ompanies prefer to produce drugs that require little risk taking but still offer the potential for high revenues.  This strategy has created an emphasis on producing ‘me too’ drugs — drugs which have a very similar chemical formulation to drugs already on the market.  These drugs are less risky to develop because the safety and efficacy of the drugs on which they are based have already been studied.  According to one panelist, an industry representative, because the length, complexity, and expense of developing a single drug have all increased dramatically over the last 10 to 15 years, companies must choose fewer drugs to develop.  As a result, they will often follow a business model that involves choosing drugs that are easy to develop, with a large market that will produce a large return on investment.

Another factor cited is "sponsors’ uncertainty over how they are to implement requirements for the safety and efficacy of new drugs."  The report notes

general agreement that the lack of precise FDA regulatory standards that outline what constitutes a safe and effective drug is a factor when making drug development decisions — weighing the safety of drugs against their potential therapeutic benefits.  Panelists generally agreed that because there are no precise standards for making these decisions, sponsors and FDA must address them on a case-by-case basis.  As a result, it was indicated that this uncertainty may lead a drug sponsor to abandon a drug rather than risk significant development expenditures.

While product liability litigation is not mentioned in the report by name, it clearly factors in to the industry’s aversion to "risk."  Moreover, at least some of the uncertainty and extra-cautious attitudes within the FDA can be traced to highly publicized — and heavily litigated — withdrawals of drugs based on safety concerns:

* * * Some analysts have reported that safety concerns during the 1990s — which led FDA to request that manufacturers withdraw pharmaceuticals including fenfluramine and dexfenfluramine (known as Fen-Phen) in 1997, Propulsid and Rezulin in 2000, and Baycol in 2001 — impacted FDA’s review requirements.  For example, a 2004 report completed for the European Commission — the executive body of the European Union — found that the withdrawals of these pharmaceuticals from the market affected FDA’s implementation of its regulatory standards.  According to this study, FDA began to demand more complex clinical trials that called for more testing on: (1) how drugs interact with each other, (2) the effect of drugs on liver toxicity, and (3) the relationship of drugs to cardiac risk. In addition, according to several drug development experts and some industry analysts, FDA has been requiring more lengthy and complex clinical trials, which call for more patients and increased costs. . . .

Commenting on the GAO report, Ronald Bailey (Reason Magazine, Hit & Run, "What’s to Blame for Fewer New Pharmaceuticals?," Dec. 20) summarizes:

Why have FDA regulators become more cautious?  Because, as Harvard Business School professor Regina Herzlinger explains in her May, 2006 article, Why Innovation in Health Care is So Hard (not online): ‘Officials know they will be punished by the public and politicians more for underregulating — approving a harmful drug, say — than for tightening the approval process, even if so doing so delays a useful innovation.’

I will venture to suggest that the FDA’s increased obsession with safety may be killing more people than it saves.  How about a GAO study on that question?  After all, if it takes the FDA ten years to approve a drug that saves 20,000 lives per year that means that 200,000 people died in the meantime.

The full GAO report, "New Drug Development: Science, Business, Regulatory and Intellectual Property Issues Cited as Hampering Drug Development Efforts," is available for viewing and download here [PDF].

Filed under: Europe, fen-phen, medical