It is not all about the lack of positive clinical trials
Many scientific papers have been written about the crisis caused by the lack of groundbreaking new drugs for treatment of disorders of the brain. Most of these pieces have dealt with the lack of new mechanisms of action or of treatments that truly modify the course of the treated diseases/disorders. However, as badly as we need new drugs – and we are all eager to see clinical trials with positive findings – there are other factors than hamper the advancement of knowledge.
One of these is the lack of solid clinical trials with negative results. Science is based on strong inference, and in order to advance, we need to change paths when one way is proven wrong. Unfortunately, this is not what usually happens in clinic trials of treatments for brain disorders. All too often, we see that negative trials do not lead to the abandonment of those treatments or mechanisms of action. It is not only very ineffective to conduct trials that, if negative, will not be informative but also ethically reprehensible, as we are exposing subjects to treatments in trials that will not provide useful information. The rule in our field is the opposite of what it should be, i.e., if the results of an underpowered trial or one with an ill-defined heterogeneous population are negative, then more trials are conducted. Negative trials should not lead to the performance of further trials with the drug in question. Negative trials can be less fortunate than non-negative trials, but they should be no less informative.
ECNP Preclinical Network Data Prize
We should also make sure that informative negative findings are published, as they are helpful to all scientists working in the area of the research. The ECNP’s Preclinical Data Forum has recently announced what is believed to be the world’s first prize for published “negative” scientific results, the ECNP Preclinical Network Data Prize. The €10,000 prize, aimed initially at neuroscience research, is intended to encourage publication of data where the results do not confirm the expected outcome or original hypothesis. We are very grateful to Thomas Steckler and Anton Bespalov who put together this award, and Cohen Veterans Bioscience, which generously provided funding. Full details of how to apply for the ECNP Preclinical Network Data Prize can be found on the ECNP website.
Another even more problematic issue that hampers advancements in knowledge is faked trials. We should be much more proactive in identifying and combatting such trials. For instance, there is a group of clinical sites in Iran that has published more than 300 papers in recent years, all of them positive! – with results not replicated anywhere else and with papers written using the same methodology and only minor changes (basically, in the names and doses of the drugs used). The most unexpected drugs have been purported to work for the enduring negative treatment of schizophrenia, refractory depression, Alzheimer’s disease, and acute ischemic stroke. An additional problem is that those studies are then included in meta-analyses, thus obscuring their results. In health care systems there are ways of approaching patients who abuse those systems (e.g., reporting of cases of factitious disorders or Munchausen patients in all sites that deliver health care, so that the network of those sites does not expend unnecessary resources). The same should apply to editors of journals, who should all be aware of networks of sites that apparently publish fake studies.
At this time of the year, I would not want to take leave of you without wishing you all the happiest of holidays and extending to you my best wishes for a truly successful 2018!