Someone I know has been left disabled after participation in a clinical trial of an experimental drug. Advised that no conventional treatment existed for his rare multisystem disease, he deliberated before dipping his toe into the world of clinical trials.

After receiving one dose of the experimental drug, he told the principal researcher of new and troubling symptoms. The second dose greatly exaggerated his troubles. The drug was stopped but not before leaving him with profound nerve damage, chronic pain, and worse of all, the inability to use his dominant hand.

The patient alleges that the principal researcher did not take his complaints seriously, that there was a lack of good communication and that in the eagerness to enrol the patient, the process of informed consent was lax. An intelligent professional, he laments that had the rare but serious toxicities been explained better he would never have consented to the trial.

Having watched him caught between doing nothing and participating in an experiment, I feel very sorry that his choice led to an extreme outcome where his decline is now marred by depression and self-blame about having made a bad condition worse.

I have also come to admire his grace through an unimaginably difficult period. It would be fair to say that he is disillusioned and his trust in the clinical trials process has been fractured.

Recently, a prominent Australian trial was retracted by the Journal of the American Medical Association, a full two years after publication, when it emerged that the principal researcher had concocted patients and fabricated data about a common blood pressure drug and its impact on walking time in patients with peripheral vascular disease.

Given the high prevalence of cardiovascular disease, the impact of a positive study in a prestigious journal is substantial and wide-reaching. The finding was quoted more than 30 times. Many doctors may have read the original conclusion and modified their practice but failed to see the retraction, including one published more recently in the New England Journal of Medicine.

The fraudulent actions of a lone researcher also left an entire institution shame-faced in its wake. For some, such accounts will cement their cynicism over clinical trials in medicine, often driven by big pharma and run by unscrupulous researchers who chase publishing fame over patient safety. More reasonable people will rightly bristle at this broad generalisation and point out the greater good from well-conducted trials which advance the cause of all patients.

We are by now familiar with the worldwide crunch in healthcare research funding even as we clamour for smart innovations and new discoveries. Publishing original research in top academic journals is a time-honoured way of gaining medical immortality, and in turn attracting better funding. Therefore, we should almost expect that despite ticking the boxes on research integrity and ethics there will be a subset of researchers who will try to outsmart the system. Many will be caught but unfortunately, some will escape detection and censure.

The hallowed mission of improved patient care sabotaged by arrogant and dishonest researchers is by now a familiar story, one that has institutions in knots over how to strengthen their monitoring systems. This is why I barely took notice of the words “research” and “concealment” in a journal I was reading recently. But I am glad I read on because the study shone light on an important but invisible aspect of clinical trials: deception by research participants.

The research referred specifically to healthy volunteers who are paid to compensate them for their time and inconvenience. (In trials involving real patients, there is typically no payment but travel costs and meals may be provided.)

The researchers studied 100 patients who had participated in at least two studies in the past year or at least four in the last three years. An astonishing three-quarters of subjects reported concealing some health information from researchers to avoid exclusion from enrolment in a study. One-third concealed health problems and use of prescription drugs and 20% recreational drug use. A quarter exaggerated their symptoms in order to qualify and perhaps more worryingly, 14% simply pretended to have a health condition in order to join the trial. 

These high figures were startling. Why did these participants lie? Was it the financial incentive, embarrassment about disclosing private information or something else? Was a trial their only way of seeking medical help or was there a distorted altruistic instinct at play? Would their CV be embellished by the mention of being a healthy volunteer in the cause to banish a disease? The researchers observed that the frequency and context of the behaviour were unclear. This study was small but there have been longstanding ethical concerns about paying people to participate in clinical trials.

An essay in the New England Journal of Medicine highlights an even more troubling side to the story. The writers observe that by falsifying their account, participants undermine the integrity of the entire study by biasing the data. 

Whether a trial is studying the efficacy of a test or the toxicity of a drug, participants who report their experience with anything less than total honesty can substantially alter findings, leading to the discontinuation of a valuable trial or conversely, continuation of an unsafe one. 

Serious toxicity can be attributed to the experimental medication when the culprit is an illicit drug or a drug interaction. Alternatively, a drug trial that mistakenly includes patients suffering from a given condition instead of healthy volunteers may be biased in favour of the drug. 

The authors recall the dramatic but cautionary tale of a participant who arrested and died during a sleep study due to an electrolyte imbalance thought to be related to the prescribed lithium when in fact it was caused by anorexia and self-induced vomiting. Had the patient disclosed her anorexia, the researchers would have excluded her from the study but directed her towards the help she needed.

Progress in medicine comes from standing on the shoulders of volunteers and patients who are by and large altruistic participants in research. But since less than 5% of the population participates in clinical trials, even a small number of dishonest individuals can sway results in significant ways to affect our health at a population level. And yet, evidence is our best friend when it comes to selecting the most appropriate antibiotic, the safest antipsychotic or the best surgical technique. 

Doctors must pause to think if the evidence-based treatment we think we are practising has been acquired from research conducted with total integrity. For researchers and ethics committees, this means intensive vigilance of institutional ethics. For clinicians, it means applying a ceaselessly inquiring mind to the reams of data thrust upon us everyday and not being afraid to acknowledge that in many areas of medicine, there is no one right answer.

And importantly, for patients, it means being unafraid of asking questions and having a curious mind about the strength of evidence a doctor’s advice is based on. With the power imbalance between doctors and patients this isn’t easy but more than ever, it’s necessary, and I think we have to enable our patients to do it. 

The patient I describe is dismayed at his experience of researcher misconduct and I hope he finds some consolation in an apology. Meanwhile, all of us, living with common conditions from blood pressure to depression, should be wise to the potential of healthy volunteer participants in clinical trials to impact the decisions made about our own health. For all our sakes, researchers and participants must strive for better.