Drug Safety: A Matter of Trust!

Those Canadians are at it again! Quick they are at being contrary to the U.S. This even extends to drug safety issues.

As reported in the WSJ on 9 February 2005, the U.S. and Canada differ on whether or not the attention-deficit drug ADDERALL is safe ("Why U.S., Canada Differ on Safety Of Attention-Deficit Drug").

Health Canada -- the equivalent to the FDA in Canada -- instructed Shire BioChem Inc., the manufacturer of ADDERALL XR to withdraw the drug from the Canadian market (see "Health Canada suspends the market authorization of ADDERALL XR , a drug prescribed for Attention Deficit Hyperactivity Disorder (ADHD) in children").

The FDA has not followed suite in the U.S. In an advisory it said: "FDA does not feel that any immediate changes are warranted in the FDA labeling or approved use of this drug based upon its preliminary understanding of Health Canada's analyses of adverse event reports and FDA's own knowledge and assessment of the reports received by the agency."

These days, anything the FDA has to say about drug safety -- especially if it is contrary to what its Canadian and UK regulatory counterparts have to say -- may understandably be taken with a grain of salt. Critics of the FDA have questioned not only its ability to fairly evaluate drug safety issues but also its criteria for safety:

"[FDA believes] a drug is safe until you can show with 95% or greater certainty that it is not safe," said FDA whistleblower David Graham before a Senate committee. "This is an incredibly high, almost insurmountable barrier to overcome. It's the equivalent of "beyond a shadow of a doubt." And here's an added kicker. In order to demonstrate a safety problem with 95% certainty, extremely large studies are often needed. And guess what. Those large studies can't be done." (see the upcoming February Issue of Pharma Marketing News).

It appears that Canada and the US (and the UK and the US, maybe even the whole world outside the US and the US) have different paradigms by which they view drug safety. Maybe Canada and the rest of the world outside the US are too quick to pull drugs from the market without adequate scientific evidence?

But, what is "adequate scientific evidence"?

If two renowned organizations with access to the same data and with staffs of medical experts can't agree on when a drug is safe or not, how can an ordinary, non-scientifically-trained patient do so? Even some physicians are confused: "From the doctor's point of view, I find it very confusing and worrisome when two different agencies using the same databases reach very different conclusions," said Murali Doraiswamy, psychiatrist at Duke University Medical Center (WSJ article).

Some FDA regulators are also confused - "We found [the reported cases of death] difficult to interpret and ambiguous," said Dr. Temple, director of the office of medical policy in the FDA's drug center. Is this a case of the FDA's 95% certainty "rule" or honest scientific appraisal of benefit vs. risk?

I wouldn't attempt to answer that question. My only point is that as long as the FDA's ability to fairly judge drug risk is under a cloud of suspicion for reasons that I point out in the article "Does the FDA Need to be Overhauled?" in the upcoming February Issue of Pharma Marketing News, then we -- and I include physicians as part of "we" -- have no way of knowing who to trust.

To improve public trust, the FDA needs to be overhauled so that its drug safety function is separated from its drug approval function. In his Senate critique of the FDA, Dr. Graham said: "The same group that approved the drug is also responsible for taking regulatory action against it post-marketing. This is an inherent conflict of interest."

A large majority (84%) of respondents to a Pharma Marketing News survey agreed or strongly agreed that the job of monitoring safety approval should be separated from that of approving drugs.

The FDA, on February 15, announced a new independent Drug Safety Oversight Board to oversee the management of drug safety issues (see "FDA Improvements in Drug Safety Monitoring"). The plan, however, has already come under attack. The board will have no powers other than to advise the FDA and publish findings on a public web site (the rules for doing so have not been revealed). The board is also internal and will be comprised of FDA staffers and other government employees.

As reported in WSJ Online ("FDA Offers Placebo"):

Merrill Goozner, director of the Integrity in Science Project at the Center for Science in the Public Interest, suggested that the new board would be toothless without greater independence, funding and authority. He added that it should be peopled with full-time staff, rather than pulling government employees from other jobs. "This is a full-time job," he said. Independent monitors "should be the cop on the beat -- not somebody called in once a month to ruminate on the question of whether there's crime."

Also, there needs to be a better program for drug safety surveillance AFTER a drug is put on the market. As the author of the cited WSJ article stated: "The disagreement between the two national health regulators .... is an extreme example of the problems of limited data available on the safety of marketed medicines."

"There's no right or wrong because there's no science." -- Brian Strom, a professor at the University of Pennsylvania.

Left without adequate science to make decisions, the public and medical community can only put their trust in their regulatory agencies. "I'm going to follow the FDA. They're our agency," said a physician quoted in the WSJ article. Unfortunately, under the current drug safety regime at the FDA, such trust may not be warranted.