From Eminence to Evidence
The evolution of traditional medical practice to an approach based on scientific evidence and reasoning has improved patient outcomes enormously, and is one of the most important transitions in healthcare we have made to date. But why was there a need for change in approach to medicine?
Further, despite countless clinical trials being conducted every year, why are the ‘miracle’ drugs and treatments we see in the media not making it to the bedside? Billions of dollars are invested into clinical research annually in the UK alone, and up to 85% of research never gets translated into practice. It is clear that there needs to be a greater push for scientific evidence for medical treatments to improve patients’ overall outcomes on a large scale.
Generations of established medical knowledge have been passed down largely without being challenged by scientific evidence – until now, that is. The traditional practice of medicine has a number of flaws, including a lack of solid proof for the effectiveness of treatment, implicit and explicit bias, which could put a patient’s life at risk.
The clear downfalls of this traditional approach have led to the emergence of clear standard protocols guided by scientific evidence, giving rise to evidence based medicine (EBM), which now predominates our approach to clinical practice.
EBM relies heavily on randomised clinical trials (RCT), along with longitudinal observational studies where treatments are rigorously tested across three stages (four in Australia) to ascertain their effectiveness and safety compared to currently available options. These trials are rigorous, and standards are high. As such, a large proportion of treatments tested generally fail Phase II or III due to safety concerns. In some cases, the treatment being tested proves to be no more or even less effective compared to current treatments, as seen in the Cogane trial where placebo and treatment made no difference in Parkinson’s disease.
Over the past decade, various drugs that were initially deemed safe for human consumption have been found to carry unacceptably high risks (or unacceptably low benefits), and have been subsequently withdrawn.
In 2004, the anti-inflammatory drug rofecoxib (Vioxx) was immediately pulled from the shelf after more than 30,000 people suffered cardiovascular events. The study that showed its efficacy was poorly designed and lacked investigation into potential side effects resulting from the drug’s effect on other body systems. These catastrophic events occurred despite rigorous testing on animals, showing such models may not be a true reflection of human physiology, irrespective of genetic similarity.
In 2006, the case of the immunomodulatory drug TG1412 further illustrated the failure of translating animal studies to human trials, landing six men in ICU due to multiple organ failure and brain swelling. Interestingly, the dose given was 500 fold less than what was deemed safe in monkeys during the pre-clinical phase.
As we can see, clinical trials have multiple potential shortcomings, ranging from problems with the efficacy of the drug itself, to study design and the issue of misleading and falsified published data.
It is of paramount importance to provide complete dataset from a trial including limitations and adverse effects of a treatment. Many pharmaceutical companies and researchers fail to publish some studies when the treatment shows no therapeutic benefit. These negative findings are also being more likely to be rejected by medical journals in favour of positive findings – a phenomenon widely known as publication bias.
However, researchers and government funding bodies are urging for detailed reports of all results from trials, both positive and negative, to be presented to give a more global picture of how the treatment works, such as through the AllTrials initiative. This allows any issues with the treatment to be addressed in a more timely and effective manner, thereby preventing wasting resources on unfruitful treatments.
However, even after a treatment is deemed safe and effective, how long does it takes to implement it in the clinical setting? One might reasonably conclude a year or two, or perhaps even up to five. Shockingly, the lag between trial study to clinical practice has been shown to take up to seventeen years.
This is a multifactorial issue that not only involves researchers and pharmaceutical companies. To combat this delay in translational medicine, health professionals also need to become more responsive and flexible in their approach to clinical practice, and be ready to adopt proven effective treatments.
Many doctors are most comfortable with clinical treatment options which have been proven to be safe and effective. However, this reassurance in their chosen treatments at times creates a hesitance when considering new treatment options due to their lack of experience and familiarity with the proven new treatment.
One way to overcome this is to actively involve more clinicians in the early design and planning of clinical trials. This would allow them to gain firsthand insight into the rigorous testing process, as well as to help chaperone the transition of new effective treatments to reach patients faster.
It is said that a doctor should read up to ten journal articles a day to be up to date in their field – an unlikely scenario given the hours and intensity of work a clinician faces regularly. The pressure is on medical professionals to keep up with the rapid developments in biomedical science field, and thus on an individual level too, it is ever more challenging for doctors to stay receptive to the rapid changes in the field of medical science.
Over the past few decades, clinical trials have become central to evidence based medicine in allowing researchers and doctors to assess new treatments in different contexts and gain a better understanding of how they work in patients. However, all data from studies need to be published to present an unbiased picture of the treatment and best safeguard patients.
Ultimately, however, we need more clinicians to be involved in trial studies right from the earliest stage of design and planning. The challenge here is to make the transition from bench to bedside shorter and smoother. Making the people at either end the same people would be a good way to start.
The views and opinions expressed in this article are those of the author and do not necessarily represent those of the Doctus Project.