Difficult conditions can be difficult to study: the journey of a little white pill

human_subjects

The problems with human subjects
Credit: xkcd

It all starts with a cause. Of course it does. Be it malaria, Alzheimer’s or something else – there is a reason to start looking for a cure. Sometimes, it’s easy. Traditional healing plants are obvious avenues for drug discovery. Sometimes, it’s hard. What do you do when bacteria become resistant to all known drugs? Or if you just don’t understand a disease enough to develop something that will target the underlying cause rather than just the symptoms. Whatever road is taken, drug development has to tick certain boxes, and contend with certain politics, before a pill ends up in your bathroom cabinet.

The most exciting phase perhaps is the discovery phase. Imagine how Fleming must have felt when he discovered penicillin. Of course, once you’ve discovered it, the potential drug needs to be tested.

thermometer-1539191_640The first step is to discover whether it will do serious harm, using preclinical trials. This is done in laboratory trials (in vitro), and in animal trials (in vivo). These tests investigate the feasibility of developing the drug for humans. They also determine the dosing levels – how much of the drug is required to fix your headache but not make you feel funny with some other side effect. Only about one in a thousand compounds is promising enough to proceed to human, or clinical, trials.

We like to think of trials in their ideal condition: people pitch up to the clinic, take drugs, and come back regularly for monitoring. And of course, everyone is perfect and comes every time, never skips a dose, never lies on a questionnaire, never drops out of a trial because they don’t feel like it anymore. Of course, in reality, this is not the case. Trials have to be worked around the very particular cases that they are dealing with.

I was chatting to some colleagues at a course the other day when one of them mentioned the trials for an alcoholism study. Clinic times for this study had to be carefully planned around the days when the study cohort would be, ahem, inebriated. Study participants were required to be sober for measurements to be taken. Often the participants would simply forget about their clinic days, or still be hungover from the two days before – requiring a nurse to go and knock on their door and fetch them for the trial, and stick a drip into them to make them fit to answer questions for the trial.

So not only is there the chemical aspect to take into account when it comes to a new drug; there is the human aspect too. And that applies both for the study and for the required treatment regime. HIV positive people have to take ARVs like clockwork – and let’s be honest, who even manages to have their dinner at the exact same time each day?  Treatment regimes have to keep the concentration of a drug at that sweet spot between having a desirable effect, and not having side effects – but also fit into the bounds of what the average human will be able to stick to.

Looking at a little white pill in your bathroom cabinet, it’s easy to forget that each one had a history to get there. From exciting compound to trials, to treatment regimes, it can be difficult to balance it all out.

References

The Drug Development and Approval Process. FDAReview.org. Available at: http://www.fdareview.org/03_drug_development.php

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