On May 20, 1747, James Lind pioneered a scurvy trial on board the HMS Salisbury. Providing some crew members with two oranges and one lemon per day, while others were given cider, vinegar, sulphuric acid or seawater, along with their normal rations, Lind’s experiment is ranked as one of the first clinical trials in the history of medicine. More than 250 years later, the anniversary of his groundbreaking work is celebrated as International Clinical Trials Day. Held annually by the National Institute of Health Research, the principles of Lind’s work still form the basis of modern clinical trials.
In a commentary for Trials, Dr David Sackett offers his perspective on more recent developments in clinical trials, evaluating the changes that have taken place over the last decade, and contemplating the future of trial practice. One noticeable change, Dr Sackett notes, is that patients are becoming ever more informed and demanding: ‘Patient groups are increasingly holding trialists’ feet to the fire and forcing us to honour our obligations to them and their diseases, illnesses, predicaments, and other patient-relevant outcomes, rather than focusing only on our interests and those of the drug and device industries.’ The commentary also highlights the growing number of trials conducted in the developing world by trialists hailing from those regions, and the higher levels of recognition this research is receiving.
The future of clinical trials looks positive, not least in the way trial results are used. Just as registering clinical trials has become the norm, there are calls for the publication of all trial results (regardless of outcome) to be an established practice. The AllTrials initiative, launched in January 2013, is gathering pace, gaining support from the European Medical Agency, many patient groups, and ‘big pharma’ giants, most notably GlaxoSmithKline which is now dedicated to releasing all of its trial results online. The shift towards publication of all results is an important one in the eyes of many researchers. A combination of journals dedicating publication space to more interesting positive findings, and reticence on the part of researchers to publish unwelcome results has led to publication bias and a wider distrust among doctors and patients as to whether the interventions they are prescribing and taking are really the best for the patient. In a Q&A with Biome, the new online magazine from BioMed Central, Dr Ben Goldacre a co-founder of the AllTrials initiative, discusses the campaign, and how it can dramatically change the landscape of trial reporting. Dr Goldacre comments that ‘doctors, patients, payers, and researchers need access to all the results, of all the trials that have been conducted on a treatment, in order to make informed decisions about which is best. The idea that trial results should be withheld is ludicrous, it simply breaks evidence based medicine, and exposes the medical profession to justified mockery.’
The shift towards publication of all results can be seen as part of a wider move towards making research more available to an increasingly educated public, as well as those researchers and clinicians that directly use results from such research. Last year, the UK government commissioned the Finch report, which advised parliament to demand that all research funded by public money be published as either ‘green’ or ‘gold’ open access. Universities and science minister, David Willets, promptly made the announcement that £10 million would be earmarked to aid the introduction of such a policy.
As a pioneer of open access, BioMed Central has seen the benefits that opening up research can bring. Tapping into the need for more transparency in clinical trails, the journal Trials and all other BioMed Central journals that publish trials and trial protocols, demand that authors register their clinical trials as a condition of submission. To that end, BioMed Central runs Current Controlled Trials on the behalf of ISRCTN, the UK’s trial registration service. To date, the register holds records of over 11,500 trials. BioMed Central also welcomes the HRA proposals ‘to make the registration of clinical trials within an agreed timeframe a condition of ethics approval’ and ‘to work with publishers to dispel the myths and perceptions about the difficulties in publishing results’.
The publication of negative results is gaining more attention among researchers, and trialists in particular. Trials journal supports the publication of negative results, alongside Journal of Negative Results, established for the sole purpose of publishing unexpected results, or results that go against the current understanding.
Today, billions of people across the globe will take drugs – from paracetamol tablets to anti retrovirals – that are life saving and life enhancing, and that have all been through a lengthy process of intense testing. Over a quarter of a millennium researchers have refined this process, and continue to do so today, ensuring that the work James Lind began on the HMS Salisbury endures.