'How do you feel about being a guinea pig?'

That's the question I ask my friends when they tell me they're on the latest medications to hit the market. As an aside, many of them have been on the NSAIDs (Non Steroidal Anti-Inflammatories) and, of course, the new COX-2 Inhibitors such as Celebrex,Vioxx, and Bextra, the latter two no longer on the market. This is the 'traditional' arthritis treatment, of course.

There's no doubt in my mind that they and the general public have placed too much faith in the regulatory authorities of Canada and the U.S - never mind the pharmaceutical companies - when it comes to trusting the efficacy of the medications they're taking. When I think of the U.S. Food and Drug Administration (FDA) and its record, and the extent to which Health Canada painfully follows their lead, I worry that the pharmaceutical industry has far too much influence on both country's regulatory systems. The FDA approval process is a de facto rubber stamp, and the Canadian approval process is veiled sufficiently to disguise any possible subjectivity. In Canada we have to use the U.S. Freedom of Information Act to access drug submission information. Processes like these make it difficult to get a handle on the issues surrounding the over 180,000 deaths annually from adverse drug reactions - the deadly tip of the 2 million hospital admission for adverse drug reactions iceberg..

Here's the Readers' Digest version of the drug approval process in North America: It's incomplete and admittedly inadequate, but the summary will give you a feel for the regulatory process.

The process, by the way, can take up to 12 years and a lot of money to be sure: $24 billion in R&D by the pharmaceutical companies in 1998. And while they are the most profitable companies in our economy, there's no doubt their industry is a high risk one.

Pre-Clinical research takes 1-3 years, averaging 18 months with research done on animals, followed by three phases of human testing followed by FDA review. Drug testing goes from the lab to animals to humans as one should expect. Animal testing is done on at least two species largely to assess how the drug gets absorbed and eliminated by organs. Of course, potential toxic effects are identified as well. Here the FDA conducts a safety review before allowing human testing to begin and New Drug Application (NDA) to be issued and controlled clinical trials can begin on humans.

Phase 1 Clinical trials identify how the new drug works on the human body and how the body gets rid of the drug. Phase 2 of the these clinical trials assesses effectiveness and safety of the drug, in addition to quantifying side effects. This phase involves a small number of people who may or may not have the disease or condition for which the drug is intended. Phase 3 is clearly the most important phase in the testing process and trials involve anywhere from several hundred to several thousand people to determine possible side effects and the overall effectiveness of the drug. However, there is no way these trials can identify all the possible side effects and adverse reactions that the drug would encounter in general use. Until 1992, the time period between NDA approval and FDA approval averaged just under two years. But that was then.

Today, in a period where many more drugs enter the market in the U.S first, pressures to speed up the approval process have begun to exert themselves. The pharmaceutical lobby, AIDS, and public demands for quicker drug approvals have led to a confluence of political compromises concerning the drug approval process. The FDA, first and foremost, has morphed into a partner of the pharmaceutical companies, a far cry from its original and truly regulatory function. Safety is now a secondary consideration. And while there are important exceptions requiring 'speed-up' for drug introduction and approval, public safety must remain paramount.

Today, regulatory systems are in crisis. Drug safety monitoring is minimal and cumbersome and the public is inured to the risks associated with drug use. Serious adverse drug reaction is simply a fact of life today and it shouldn't be. Today, most people taking medications are on multiple drugs, so now interactions are ostensibly studied when they are on the market. The trouble is it's the general population that's now the trial group.

Identifying reactions difficult and usually takes a few years to identify serious problems. A further complication is that less than 1% of adverse drug reactions are reported to the FDA's Office of Postmarketing Drug Risk Assessment because of US voluntary reporting system - Doctors see an adverse drug reaction and they have to fill out complicated forms if they want to report the reaction. Usually what happens to newly introduced drugs is this: if a serious adverse reaction is identified the product label is changed and an insert carries an advisory. The FDA rarely takes a drug off the market. After all, they approved it! This wasn't such a huge problem 15 years ago when, before 1990, only 3 or 4% of all new drugs into North America were first released into the the North American market. By 2002 it's 66% of drugs first released into North American market, so you can see how this has become a problem.

Again, in the last few years we've experienced. 2 million hospital submissions due '*solely* to adverse drug reactions, and 180,000 of them result in death.

I earlier alluded to the U.S. FDA - Canada Health relationship. Both are now in lockstep with the pharmaceutical companies now given the FDA's 'partnership' role with U.S. industry. The Canadian Medical Association Journal (CMAJ) reported on a joint review under the terms of a memorandum of understanding that Canada and the United States signed in April 2004 concerning their intention to reduce 'bureaucratic hurdles' - read 'impediments and critical scrutiny' - "for manufacturers applying to have new drugs approved in both jurisdictions, and to bring new drugs to market faster." (CMAJ 2004; 171:121). We boomers are an unhealthy lot and there certainly are pressures to introduce drugs to alleviate all those aches and pains associated with chronic degenerative diseases that will afflict almost 90% of us - if you buy into the 'attack medicine paradigm'.

Here are two articles that give you a feel for what the regulatory landscape looks like.

Women's Health Protection Groups have called for more transparency in the Canadian drug approval process.
http://whp-apsf.ca/en/documents/transparency.html

Canada's drug approval process too hasty says Mary Wiktorowicz, a York University professor who recently conducted a study comparing drug approval and recall rates in Canada with those of the United States and several countries in the European Union.

Her study is reported in an article by Christine Maki at http://media.www.thevarsity.ca/media/storage/paper285/news/2003/10/30/Science/Canadas.Drug.Approval.Too.Hasty.Says.Prof-543377.shtml

So remember, the next time you get that prescription for that miracle drug you saw advertised on TV, remember, only 50% of the problems remain unidentified. Dr. Ray Strand wisely suggests that you should wait 5 years before you take any OTC medication to reduce your chances of next being in a hospital bed.

On that last note, for an easy and informative read, I recommend Dr. Ray D. Strand, M.D., Death By Prescription: The Shocking Truth behind An Overmedicated Nation. 2003 Thomas Nelson Publishers.