Five Points For Consideration In May 2006 Circulation Editorial By Jerry Avorn, M.D.

In May 2006 the medical journal Circulation published "Evaluating Drug Effects in the Post-Vioxx World — There Must Be a Better Way", an editorial piece written by Jerry Avorn, M.D., who is associated with Harvard Medical School and Brigham and Women’s Hospital, in Boston.

Dr. Avorn’s editorial takes issue with the idea that "requiring extreme criteria for demonstrating efficacy" is the only way to be sure that we are getting adequate safety information about new prescription drugs in the aftermath of the Vioxx recall.

This Avorn editorial is in the same edition of Circulation that includes the article "Clinical trials in the wake of Vioxx: requiring statistically extreme evidence of benefit to ensure the safety of new drugs", by Michelle D. Roth-Cline, B.S.  While Dr. Avorn reaches the some conclusion that Roth-Cline does in her article — "that demanding unprecedentedly stringent tests for efficacy is a poor way to fix the nation’s drug safety problem", in Avorn’s words — his reasoning differs from that presented in the related article by Roth-Cline.

In his May 2006 editorial, Dr. Avorn raises five points for consideration which, as he explains below, are derived from the lessons of Vioxx:

The delayed "discovery" of the dangers of rofecoxib [i.e., Vioxx] and other high-profile drugs should indeed cause us to ask what additional lessons can be learned from our current debacles and prompt a thorough review of how drug risks are detected. Unfortunately, many of the lessons drawn from such case studies by regulators, clinicians, companies, and the public, including the proposal rightly condemned by Roth-Cline, have led to the wrong conclusions.

Thereafter, in this four-page Circulation editorial, Dr. Avorn briefly discusses each of the following five points:

• Wrong Lesson 1: Preapproval Studies Provide the Only Opportunity to Detect Important Drug Risks 
• Wrong Lesson 2: Either We Can Approve Drugs in a Timely Manner or We Can Learn Enough About Their Risks Before Approval, but We Cannot Do Both 
• Wrong Lesson 3: Rofecoxib Proved That Many Important Adverse Events Are Inherently Unknowable Until It Is Too Late, and Therefore We Are Unlikely to Develop Better Systems for Their Detection 
• Wrong Lesson 4: Greater Scrutiny for Adverse Events Will Impede the Availability of Important New Products and Drive Up Drug Prices 
• Wrong Lesson 5: The Best Strategy Now Is for the FDA to Warn About Everything 

Dr. Avorn concludes his Circulation editorial with both a lament and a call for action:

It is a sad commentary on the current state of drug evaluation and safety surveillance in the United States that some believe that the only way we can be sure of getting adequate safety information is by requiring extreme criteria for demonstrating efficacy. Fortunately, other solutions are possible that are more scientifically rigorous, clinically appropriate, and feasible.  All that is lacking is the political will to implement them.

Let’s hope that our lawmakers in Washington heed Dr. Avorn’s suggested solutions and, more importantly, act on them before we have another drug-safety debacle like Vioxx.

(Posted by: Tom Lamb)