DRUG SAFETY TESTING - a Bittersweet Pill, Part I

For the pharmaceutical industry, the topic of drug safety testing tends to be a case of 'damned if you do and damned if you don't'. It certainly isn't easy going from the decision to jump on board a new therapeutic area, selecting an appropriate drug candidate, to (if the company is lucky) finally obtaining a license to market that potential blockbuster! Part of this process is showing that a new drug is safe for the patient. This exercise alone requires a massive effort that, however unpleasant, is a mandatory requirement by the various regulatory authorities that govern national and international therapeutic markets. Such agencies as the Medicines and Healthcare products Regulatory Agency (MHRA), the European Medicines Agency (EMEA), and the U.S. Food and Drug Administration (FDA) therefore have an important responsibility in issuing drug licenses. Even then, this is not a guarantee against severe side effects and sometimes it all goes wrong only after the drug is launched - patients may end up suffering from drug toxicity that even causes death. So what might have happened on those occasions? Why didn't preclinical animal safety studies and clinical trials pick up any signs of toxicity?

I intend to break down the whole process of drug safety assessment in a series of postings, in which consideration will be given to those particularly challenging avenues such as the predictivity of animal studies and clinical trials and that inextricable issue of human vs. animal rights. I'll give attention to advances in in vitro screens (cell models), the balance between cost and benefit, and the interplay between safety and efficacy (how well a drug works).

For now, let's remember that our bodies do try their best to battle the many ailments that strike us through our lifetime. It's just that on occasion it isn't enough, so we turn instead to various concoctions to speed up the healing process, alleviate our suffering, or tackle the diseases that our bodies' defence systems simply can't cope with. We also take these remedies with the hope that we are cured quickly and safely, when few actually meet both expectations. For those of us who prefer to seek our GP's advice and accept recommended prescription drugs, we also often (and naively) presume that these will do the job to great aplomb - a preceding faith that may actually afford an important placebo effect (something to look at in later postings).

These expectations are of course the crunch point for all pharmaceutical companies. In order to solicit approval from the regulatory authorities, a drug candidate must indeed be demonstrated convincingly to work effectively and safely. In reality this is a multifaceted statement underlined with assumptions. For example, the claim that a drug works can be interpreted as 'we showed in our studies that so long as the patient conforms to the appropriate dosing regimen, the drug reaches the target site(s) in the body in sufficient quantities to be effective, remains there long enough to do the job and other diseases or conditions do not interfere with this process, only a few and tolerable side effects may occur, and the resulting benefit of taking the drug is worth the risk and the financial cost.'

So, there we have it - a drug must work (be efficacious) and be safe. Sounds obvious, except generating the data to prove this to the authorities can be a major headache and even end in disaster. Look out for future postings on drug safety assessment. In the meantime, keep taking the pills - or should you?????