(Updated)-- Last summer British researchers provoked concern when they published a paper raising the possibility that by following an established guideline UK doctors may have caused as many as 10,000 deaths each year. Now they have gone a step further and published an estimate that the same guideline may have led to the deaths of as many as 800,00 people in Europe over the last five years. The finding, they write, "is so large that the only context in the last 50 years comes from the largest scale professional failures in the political sphere." The 800,000 deaths are comparable in size to the worst cases of genocide and mass murder in recent history.
In their new article published in the European Heart Journal, Graham Cole and Darrel Francis continue to explore the extent and implications of the damage caused by the Don Poldermans research misconduct case. [Update: the EHJ article has been removed from the EHJ website. For more on this see the bottom of the story.] The earlier paper demonstrated the potentially large and lethal consequences of the current European Society of Cardiology guideline recommending the liberal use of beta-blockers to protect the heart during surgery for people undergoing non cardiac surgery. The guideline was flawed because it was partly based on unreliable research performed by the disgraced Poldermans (who also served as the chairman of the guideline committee). This may seem like a highly technical question but it effects many millions of people and may, as Francis and his colleagues have demonstrated, led to many thousands of unnecessary deaths.
The new article, the first of two parts, makes no new scientific claims, but instead begins to consider the broader implications of the story. Cole and Francis briefly consider the dilemma of clinicians who may "feel unable to act in contravention of guideline recommendations recognized as ‘state-of-the-art’ by the European Society of Cardiology" and who may even be penalized for failing to follow guidelines.
They note that more than half of the lives lost-- potentially more than 400,000-- may "have occurred after the research was discredited," though some of the damage may have been mitigated if doctors changed their practice after reading about the controversy. (There was a 2 year delay after the start of the Poldermans affair until the ESC withdrew the beta-blockade recommendation.)
Cole and Francis argue that much needs to be changed in the application of medical research:
The aviation profession has led the way in systems to prevent, recognize, study, and learn from professional failures. Clinical medicine is now following the same path. We must develop similar systems for research.
In the second part of their article, to be published in two weeks, Cole and Francis will raise the possibility that the responsibility for misconduct lays not just with misguided researchers like Poldermans but also the institutions and the institutional leaders that provide uncritical support to research factories. Further, they will discuss the role of journal editors and, even, journal readers.
Comment: It would be easy to dismiss the views of Cole and Francis as outrageous and overly provocative. After all, with the exceptions of Josef Mengele or Hannibal Lecter, doctors aren't usually murderers, at least not intentionally. My best guess is that the Don Poldermans of this world strongly believe they are doing good, though that may lead to cutting corners and, then, covering up the corner cutting.
But there are good reasons to think that this sort of provocation is necessary. There is, it has now become clear, a general lack of concern and response to evidence of scientific fraud and misconduct. Journal editors, deans, department chairs, and others seem more concerned with protecting the reputation of their respective institutions than aggressively upholding the integrity of science and research. Of course, defending science and maintaining the reputation of an institution should not be opposing choices. But since they are, perhaps a little provocation is in order.
Update (January 17):
In an highly unusual move the editor of the European Heart Journal has removed the article by Cole and Francis from the journal. No notification or explanation appears on the website. though the headline is still present. I asked Thomas Lüscher, the EHJ editor, for an explanation. Here is the response I received:
Thank you for your mail. As the editor-in-chief of the Eur. Heart J. I have to inform you that this piece, although published online in CardioPulse contains scientific statements that do require peer-review. Unfortunately, this was bypassed by the handling editor and thus I had to act appropriately and correct this mistake.
The authors have been informed about this measure and will hear from us in the near future as soon as the reviews are in. This does not in any way preclude any decision on the article.
Thank you for your understanding, the administrative mistake is on our side. Please note that the Eur. Heart J. is not a newspaper and hence has to follow the outlined rules of peer review.
In response to followup questions I sent to him, Professor Lüscher sent the following additional comment:
I do hope that you understand that the EHJ is high impact journal with stringent peer review. CardioPulse publishes also non-scientific features on societies, countries and alike which are exempt for that process. In this very case, however, as in some others we had in the past, I instructed the editor in charge to discuss with me first whether this needs peer review. Unfortunately, this slipped his attention. I strongly feel that this is required here and one of the authors already communicated his understanding for this. Peer review has nothing to do with censorship, in fact we do this with 3500 manuscripts per year.
In this case, it also appeared necessary as in the meantime also other articles have appeared on the topic. Furthermore, we cannot discuss this issue without referring to the ongoing process within the ESC.
Finally, it is correct that the guidelines have not been retracted as so for the main trial of Poldermans in the NEJM has not been retracted either. Neither the NEJM nor the investigative committee issued such a recommendation. Hence we have to look at this issue in a much balanced manner as the different trials differ in design, molecule, dose, regimen among other. Finally, we have to consider recent registry data. It is the mission of the EHJ to provide first class information and if the reviewers agree with the content of a given paper, this is fine. If not, revision may be required. As I said, we are a scientific journal and not a newspaper.
Thank you for your understanding. You will certainly be informed about the outcome in due time (usually this take 21 days).
Second Update (January 18):
The authors of the "disappeared" article, Graham Cole and Darrel Francis, sent the following statement:
Our article is a narrative of events with a timeline figure and a context figure. We had not considered it to contain scientific statements, but we admit that it does multiply together three published numbers.
It is not an analysis of individual trials considering design, molecule, dose and regimen. We published last year the formal meta-analysis under stringent peer review in Heart and addressed the questions, including dosing, in that paper and associated correspondence.The first of our two EHJ articles merely says that our community, which races to take credit when research-led therapy improves survival, must be equally attentive to the possibility of harm. The leverage of leadership means the magnitude of either may be far from trivial.
Where our article relayed numbers, we made clear that alternative values were possible. The focus for readers was on how serious the consequences can be when clinical research goes wrong.
We thank Prof Lüscher for highlighting the scientifically important point that the pivotal trial, DECREASE I, has not been retracted by NEJM because the investigative committee did not recommend this. Unfortunately the committee could not have done so, because DECREASE I was outside its brief, displayed on the first text page of the first committee report. Can readers suggest why DECREASE I, from the same trial family, was exempted from inquiry?
We admire Prof Lüscher’s diligence in sending for peer review what we thought was merely multiplication. We await the review of the pair of articles. The first narrated one instance of a pervasive problem. The second suggests what each of us can do to reduce recurrences.
We respect the process Prof Lüscher has set in motion. We ask readers to join with us, and the journal, in maximizing the reliability of clinical science for the benefit of patients.
