Testimonials from 1892 to Today

RESEARCH

Offline: What is medicine’s 5 sigma?

“A lot of what is published is incorrect.” I’m not allowed to say who made this remark because we were asked to observe Chatham House rules. We were also asked not to take photographs of slides. Those who worked for government agencies pleaded that their comments especially remain unquoted, since the forthcoming UK election meant they were living in “purdah”—a chilling state where severe restrictions on freedom of speech are placed on anyone on the government’s payroll. Why the paranoid concern for secrecy and non-attribution? Because this symposium—on the reproducibility and reliability of biomedical research, held at the Wellcome Trust in London last week—touched on one of the most sensitive issues in science today: the idea that something has gone fundamentally wrong with one of our greatest human creations.

The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness.”

Can bad scientific practices be fixed? Part of the problem is that no-one is incentivised to be right. Instead, scientists are incentivised to be productive and innovative. Would a Hippocratic Oath for science help? Certainly don’t add more layers of research redtape. Instead of changing incentives, perhaps one could remove incentives altogether. Or insist on replicability statements in grant applications and research papers. Or emphasise collaboration, not competition. Or insist on preregistration of protocols. Or reward better pre and post publication peer review. Or improve research training and mentorship. Or implement the recommendations from our Series on increasing research value, published last year. One of the most convincing proposals came from outside the biomedical community. Tony Weidberg is a Professor of Particle Physics at Oxford. Following several high-profi le errors, the particle physics community now invests great eff ort into intensive checking and rechecking of data prior to publication. By filtering results through independent working groups, physicists are encouraged to criticise. Good criticism is rewarded. The goal is a reliable result, and the incentives for scientists are aligned around this goal. Weidberg worried we set the bar for results in biomedicine far too low. In particle physics, signifi cance is set at 5 sigma—a p value of 3 × 10–7 or 1 in 3·5 million (if the result is not true, this is the probability that the data would have been as extreme as they are). The conclusion of the symposium was that something must be done. Indeed, all seemed to agree that it was within our power to do that something. But as to precisely what to do or how to do it, there were no firm answers. Those who have the power to act seem to think somebody else should act fi rst. And every positive action (eg, funding well-powered replications) has a counterargument (science will become less creative). The good news is that science is beginning to take some of its worst failings very seriously. The bad news is that nobody is ready to take the first step to clean up the system.

Dr. Richard Horton, the current editor-in-chief of the Lancet – considered to be one of the most well respected peer-reviewed medical journals in the world.

http://www.thelancet.com/pdfs/journals/lance/PIIS0140-6736%2815%2960696-1.pdf

Vol 385 April 11, 2015

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Despite annual revenues approaching $1 trillion, the global pharmaceutical industry has lately experienced a critical decline in the rate of profit, for which it lays most of the blame on regulatory requirements. A US think tank has estimated the cost of new drug development at $5.8 billion per drug, of which 90 per cent is incurred in Phase III clinical trials mandated by the US Food and Drug Administration and similar agencies in Europe.41 (These are tests administered to large groups of human subjects in order to confirm the effectiveness and monitor the side effects of new vaccines and other medicines.) The international business consulting firm McKinsey & Company called the situation “dramatic” and urged Big Pharma executives to “envision responses that go well beyond simply tinkering with the cost base” – primarily the relocation of clinical trials to emerging markets, where drug safety testing is seen as relatively cheap, speedy, and lax.

Vivan Hunt et al., A Wake-Up Call for Big Pharma, McKinsey & Co, Dec. 2011, http://www.mckinsey.com/insights/health_systems_and_services/a_wake-up_call_for_big_pharma; Michael Edwards, R&D in Emerging Markets: A New Approach for a New Era, McKinsey & Co., Feb. 2012, http://www.mckinsey.com/insights/winning_in_emerging_markets/r_and_38d_in_emerging_markets_a_new_approach_for_a_new_era .