The crux of trials 101:- It is neither cost-effective nor practically feasible to conduct life long studies of drug usage in chronic conditions. For obvious reasons, it would be very difficult to find a stable cohort of patients who would wish to participate in research indefinitely, especially alongside dealing with a difficult medical complaint. The emphasis falls therefore, on short-term tolerance i.e. pharmacodynamics and pharmacokinetics. Simplified, this is how the drug reacts in the body and how the body reacts to a drug, respectively. In pragmatic terms, this involves assessing a given bunch of data points such as, absorption, distribution, metabolism, and excretion. Under these umbrellas, there are a number of vital specifics, such as dose ranging and half-life i.e. time taken for the drug to metabolically reach 50% of the original dosage concentration. Then of course there’s efficacy and side effects, or adverse events. This is not an exhaustive list, but a means to address the point that, such check boxes fit neatly within a given study phase and specific assessment parameters.
For me the grey area arises in the fact that every human body is inherently different. We are all genetically unique and we eat, sleep, drink and cope with stress differently. This biological makeup determines how our bodies function day to day. Therefore, when something malfunctions in the body, the way it manifests person to person, can also be completely unique. Add to that the million and one environmental factors which alter our physiology, and it isn’t too much of a leap to realise that any study, however meticulous, can never wholly encompass every possible human variable. Clinical trials rarely and can’t really, last long enough to reflect prolonged pharmaceutical usage outcomes. Since medicine and science is ever-evolving, there is always a new competitor star product emerging to take the spotlight, and steal away big pharma priority where funding and resource allocation is concerned.
In well renowned, active drug versus placebo studies, sample size is determined on the basis of statistical significance, or number of people needed to demonstrate that x is better than y. Protocol procedures and diagnostics to fulfill certain data criteria, is cherry picked with certain expectations in mind. If you know a given analgesic is effective in alleviating the symptoms of a headache, you ask the patient to provide a number on a pain scale, before and after taking the medication. This will give an indicator of the efficacy of the drug in question. The danger is, you might not for example, record if after two months of taking the same drug for a persistent migraine, the patient developed a strange tremor of their hands.
This is where clinical trials get a bit sketchy, as far as the numbers are concerned, but it doesn’t stop there…
My first job in academic research consisted of a blur of over worked under paid research fellows, all scrabbling over each other to get noticed by some Professor or other. They were ruthless in their work ethic, hungry for names on publications and very reluctant to offer each other even the smallest amount of help. I witnessed firsthand, medics who would fake favourable study outcomes to guarantee their sought after recognition and subsequent PhD. The worrying thing is, when such a study reached the pages of a well known medical journal, it actually influenced international treatment recommendations. After all, research facilities in hospitals are central to the development of evidence-based medicine.
I can’t say categorically if said tampered outcomes would’ve proved harmful to anyone, but it was certainly a deviation from the patient’s standard methods of treatment, and was supposedly a preventative recommendation. How can one later prove whether therapeutic intervention to stop something from happening, was the only influence in an unchanged medical baseline?
Beyond supposed long-term safety testing, Phase IV studies often look at ways to use a drug outside it’s primary indication. This is worryingly less regulated than earlier phase, first-in-human trials, as you’re dealing with an already licensed, manufactured and distributed product. The trials are conducted outside standardised trial units, by research medics in hospitals and are externally audited on a sporadic basis. This leaves clinicians with a lot of free rein to make mistakes.
Commercial research was an eye opener in a similar way to academia. I once worked on studies for a certain novel medical device, which was comparatively 20 times more expensive than standard therapy. We ran a trial for a year, which produced disappointing results and a lack of statistical significance. The company knew of a previous single centre trial, in another country, which had used a smaller sample size and produced favourable results. They opted to scrap a whole year’s worth of multi-centre, large population data to begin a new study at the hand picked location. This was blatantly done in order to gain the results needed to prevent market launch disruption. The end result, again, was a recommended therapy based on incomplete, manipulated and misrepresented data.
In other cases, companies do the same in reverse. They pre-determine which factors might reflect badly on a drug or medical device, and tailor the study protocol to avoid rigorous testing in those areas. This way they selectively focus on the positives and tactically evade any measurable factor which might give a less than glowing report.
I have since worked for Non-Profit healthcare organisations and unfortunately noticed similar mentalities. Where money could be used to implement positive change for a cause they profess to represent, certain charities would rather channel it into academic prowess. They strut around at their international conferences, rubbing shoulders with other leaders of the field, all talking with vigour about how something ought to be done about an unjust medical travesty. Then off they go to a decadent post-conference dinner and hotel stay, paid for by a generous charity sponsor who has no idea their money is supporting a whole lot of brown-nosing and not much else.
If you look at large scale NP donation distribution, the proportion of inverstment into miscellaneous fundraising can look small in comparison to the “work”, but look at the numbers:-
When a well established charity appears to know what they’re doing, by ensuring income exceeds expenditure in generating sponsorship through events etc, the benefit is clear to see. Nevertheless, one could still argue that a charity ball at the Ritz, featuring a yacht auction might not have been all that necessary (facetious not literal, but you get the picture).
Not all NPs operate with public transparency. Some do not possess the know how or moral compass to reserve support costs to efforts with a healthy return for their supposed just cause. In fact, I have seen situations where spending is barely monitored at all, to the extent where thousands gets frittered away senselessly and nobody has a clue how it happened. Scratch that, somebody probably knows very well. Developing countries are of particular concern in such scenarios, as they lack proper regulatory oversight, and so embezzlement without culpability is common place. It is soul detroying to labour under the misapprehension of a cause you believe in, only to find it is just another guise for the wrong kind of opportunist to exploit for personal gain.
Clinical trials revolve around testing potential treatments and their ability to reduce or eradicate symptoms of a given state, while keeping side effects minimal. Therein lies a flawed ideal.
As a complex organism built of a collection of organ systems, working under the conduction of a million biochemical cascades and feedback loops, we are simply not that predictable. We cannot depend entirely on package inserts to tell us how we will respond to a drug tested on individuals who are not us. Many people tolerate statins well, as a means of lowering their cholesterol, but some have crippling musculoskeletal pain, the mechanism of which is poorly understood.
There is no one-size fits all, every base covered, fullproof intervention. I believe people need to be educated on how to listen to their bodies and not be entirely reliant on a physician to make infallible judgement calls. Anything a person touches is vulnerable to human error and no profession is unsusceptible to this. That goes for every aspect of medicinal product development, from the very inception of the idea, right though to the pharmacy shelf.
Furthermore, despite trial designs revolving around high epistemic standards through randomised controlled trials and extensive peer review, they are still subject to the unavavoidable predilections of high stakes financial and professional endeavour. How much can we truly depend on yet another profit controlled system?
Although medical companies masquerade as a humanitarian pursuit, money only ever gets invested in diseases which generate the highest return. Should you find yourself falling into a rare disease bracket, which does not make lucrative blue-chip sense, you may soon realise that your symptoms are poorly understood, with limited treatment options. Unless of course, you need years and years of costly specialist medicine. In that case, your lifetime of suffering might make up for the small, highly unfortunate statistic you sit in. In short, if your illness isn’t a money maker, then by extension, neither are you.
Of course, it would be unbalanced to only preach the downside, when there have been so many excellent advances in medicine, attributable to diligent research. We certainly live far longer and suffer far less than we did 100 years ago, and this improves continuously. However, as seen with more recent horror stories of illegal circulation of unregulated pharmaceuticals, we’re in danger of taking for granted anything with a legitimate looking label, in a blister pack, as entirely safe.
We owe it ourselves to make informed decisions about our healthcare and to vigilantly protect the most valuable commodity we have.