1st place International Clinical Trials’ Day National Writing Competition Entry Frank Moriarty

Frank Moriarty is a pharmacist undertaking a PhD through the HRB PhD Scholars Programme in Health Services Research (now the SPHeRE programme). He is based at the HRB Centre for Primary Care Research, Royal College of Surgeons in Ireland and is researching potentially inappropriate prescribing and its clinical and economic impact.

Tomorrow is International Clinical Trials’ Day, celebrating the research studies which test if medical treatments are safe and effective. Though possibly not the type of trials most frequently mentioned in the media, we do often hear news about clinical trials, particularly when they have promising results. Although it may seem trivial, open and transparent availability of information on clinical trials and their findings is probably the aspect of these studies that matters most. Currently there is no obligation on researchers and drug companies to openly disclose the results of a clinical trial, or even that they are carrying one out. Why does this matter? The ultimate aim of such studies is to provide evidence which health care providers and patients can use to decide on the best treatment options to maintain and improve health. Generally, treatment guidelines are produced which compile and review all available trials to give an overall assessment of the benefits and risks of medicines. Assuming all trials that have been conducted are included, this provides a good evidence base to inform health care decisions.

However, we know that in many cases, study results are not disclosed by the researchers or drug company involved. This means the overall assessment of the evidence may be biased and not reflect the true effectiveness and safety of a treatment, particularly as non-published trials are more likely to have negative results. A paper published in 2008 in the New England Journal of Medicine illustrates this well (http://ow.ly/MwX6s). The authors of this study found that 94% of published trials were positive but when all the trials carried out were included, only 51% had positive results. By concealing a trial, this can alter the balance of evidence for a drug and make it appear more beneficial or less risky than it actually is. As a result of this publication bias, a doctor may then prescribe a medicine to a patient believing that it is the most effective treatment when this may not be the case. Lack of open and transparent trial reporting can also lead to wasted health care resources. Following the outbreak of pandemic influenza (or swine ‘flu) in 2009, many governments stockpiled the anti-viral medicines oseltamivir (Tamiflu®) and zanamivir (Relenza®). A review of the incomplete evidence available at the time from published clinical trials of these drugs suggested they reduced hospitalisations and serious complications resulting from influenza. However after repeated requests for the results of unpublished trials, the drug companies made these available in 2014 and an updated review (http://ow.ly/MARji) including these findings found that the evidence did not support the claimed benefits and also that the harmful effects of these treatments may have been underestimated. Had this been known at the initial outbreak, it is likely that less money would have been spent stockpiling these medicines and that fewer patients would have been prescribed them. The need for transparency goes beyond the final results and equally applies to disclosing that a trial is being carried out. Compulsory registration of trials before they begin would mean researchers and drug companies putting it on record that they are carrying out a study, before they know whether the results will be good or bad. This means that if the findings never become available, health care decision-makers would at least be aware that something is being hidden, whereas with unregistered trials the concealment of these results would remain an unknown unknown. A further benefit of compulsory registration is reducing the chance of “fishing” for positive results in clinical trials. It’s like baking a cake without a recipe; with infinite attempts, eventually the perfect cake would be produced by chance. Similarly without setting out a plan of analysis for a trial, repeatedly splitting up patients in different ways will eventually yield a significant benefit from the treatment in one patient group by chance. By registering a trial, researchers have to specify how they plan to analyse the study beforehand thus limiting the number of attempts to get the “right” result. Last month, there was a significant step towards achieving openness and transparency in clinical trials research. The World Health Organisation issued a statement stating results from all clinical trials should be publicly reported and calling on governments and other organisations to put measures in place to achieve this. This follows a major campaign by the AllTrials project lobbying for mandated registration and reporting of clinical trials to ensure all evidence, good and bad, is available to aid health care decisions. Many organisations and individuals worldwide have already signed the petition on the AllTrials website (www.alltirals.net) to support this cause. If you do one thing this International Clinical Trials’ Day, sign their petition to help ensure patients benefit from this vital research. Clinical trials matter, but knowing the true results matters even more.