Background

Most people would assume that when a treatment or procedure is recommended that these are based on very sound research, which has demonstrated that they will be effective and that any risks of damage to health will be kept to a minimum.

Regrettably, the reality is very different. Physicians invariably claim that their knowledge and experience is all that is needed to justify their advice. In an attempt to introduce a rigorous approach to medical practice, a few individuals have campaigned for what has become known as “Evidence Based Medicine” (EBM).

EBM was originally defined as the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of EBM means integrating individual clinical expertise with the best available external clinical evidence from systematic research (1).

The contribution of John Ioannidis

One of the most important contributors to the discussions and debate about EBM is Professor John Ioannidis of Stanford University in California. He has recently written an article in which he reflects on what has happened over the past 12 years (2). The title of the article implies that EBM has been hijacked, which gives the game away. It is fascinating to read his account of recent developments.

Here are some of the key points he makes:

  • He begins by stressing that EBM met with substantial resistance in the 1990s and 2000s. Even in the U S A, EBM and any serious biomedical research that may help intact humans was largely unwanted.
  • In the Christmas edition of the BMJ in 2000 (3) Ioannidis described how physicians are treated to a free lunch vacation in the Arabian Peninsula. As a result, a powerful politically connected doctor in Athens wrote to the medical society demanding that his medical license be revoked. Later on, at a meeting the same person stated that he could not co-exist with Ioannidis. Although no-one came to his defence, he managed to retain his medical license.
  • Essentially the EBM movement has been compromised. Here is how he describes what has been happening:

“The industry runs a large number of the most influential randomized controlled trials (RCTs). They do this very well, they score better as “quality” checklists, and they are more prompt than non-industry trials to post or publish results. It is just that they often ask the wrong questions with the wrong short-term surrogate outcomes, but who cares about these minor glitches?”

He expressed concern about the Cochrane Collaboration because it may cause harm by giving credibility to biased studies of vested interest by including the results in otherwise respected reviews. This is precisely the point I made in a blog when I referred to a Cochrane report on statins that had reached a conclusion based almost entirely on work done at the University of Oxford by Cholesterol Treatment Trialists’ (CTT) Collaboration (4). I was especially critical of the Cochrane team for its failure to have sight of the original data. It is interesting to note that Fiona Godlee, editor-in-chief of the BMJ, made exactly the same point. In an editorial she notes that proposals to offer statins to large numbers of people at lower risk remain controversial. She has written to the Chief Medical Officer in England asking for an independent review of the evidence on statins (5). The need for this was questioned in a letter from two of the authors of the Cochrane review who claimed that there was no need for an inquiry because they met all the requirements, namely “international, authoritative, independent of conflicts of interest, transparent and patient centred” (6). However in a telling response the editor explained she was advocating that anonymised individual patient data (IPD) and clinical study reports should be made available. She continued:

“You didn’t have access to these data, relying instead on the trialists’ analysis, which had only half of the IPD from the trials—the half relating to benefits, not harms. In my experience of oseltamivir, when the IPD, CSRs, and other regulatory documents are scrutinised by fresh expert eyes, new and useful information emerges that can better guide patients and doctors in their decisions”(7).

  • Many contemporary clinical investigators try to get themselves involved in multi-centre trials, meta-analyses and powerful guidelines to which they make little contribution. Vested interests dictate huge segments of the research agenda and its evidence-based aura. All of this is reinforced by professional societies and large conferences. He continues:

“It is sometimes difficult to tell whether a superb CV with a lengthy publication list reflects hard work and brilliant leadership or the composite product of dexterous power game networking, gift authorship and excellence in the slave trade of younger researchers.”

  • Ioannidis was regularly invited to participate in these multi-centre trials. On one occasion he called back and enquired about the protocol. Here is the reply he was given:

“Oh, the protocol, why would you worry about the protocol? The sponsoring company has taken care of the protocol already and will also take care of writing the paper. You don’t need to worry about minor stuff. You shouldn’t waste time with the protocol or editing drafts. We will put your name on the paper, no worries. This is what all prestigious clinical researchers do.”

  • Time and again, there have been launches of so-called “breakthroughs”, which ultimately have sunk without trace. Despite the many claims to “cure” cancer, the reality is that little progress has been made.
  • Ioannidis is especially critical of epidemiology. There is a failure to address issues such as smoking, which is killing more people than ever, while sloppy research is used as the basis for guidelines that are essentially useless. On the other hand there are corporations that use every trick to downplay any risks that might be linked to one of their products.

Conclusion

This is a very sad state of affairs. Science is being debased and many scientists seem incapable of conducting their business in an ethically responsible manner. Resources are being wasted and the citizens do not derive the expected benefits from the expenditure of public money. If there is to be any kind of progress, then the first step is to understand what has gone wrong. So we should all be grateful to John Ioannidis and others who are attempting to grapple with these issues. No doubt they will encounter huge opposition and deserve all the support they can get.

References

  1. D L Sackett (1996). http://www.bmj.com/content/312/7023/71.full
  2. J P A Ioannidis (2016). http://www.jclinepi.com/article/S0895-4356(16)00147-5/abstract
  3. http://www.bmj.com/content/321/7276/1563
  4. http://vernerwheelock.com/109-cochrane-collaboration-evaluates-statins-for-primary-prevention-of-heart-disease-2/
  5. http://www.bmj.com/content/354/bmj.i4992
  6. http://www.bmj.com/content/354/bmj.i4992/rr-2

http://www.bmj.com/content/354/bmj.i4992/rr-11