Statins - a call for transparent data

In light of “inaccurate statements” made in the Lancet by its editor Richard Horton, The BMJ has published documents relating to a complaint about two statins articles it published in 2013. The complaint was made by Professor Rory Collins to the Committee on Publication Ethics (COPE) in October 2014. Last week, Richard Horton wrongly stated that COPE had “declined to act” on Collins’ concerns.

COPE did not decline to act. The documents published outline COPE’s deliberations on the concerns raised and The BMJ’s response, and come to a clear conclusion that The BMJ “acted appropriately” in its handling of the articles which questioned the use of statins in people at low risk of heart disease.

Fiona Godlee argues that independent scrutiny of the statins trial data remains an essential next step if this increasingly bitter and unproductive dispute is to be resolved.

Harlan Krumholz, Professor of Medicine at Yale University, agrees on the strong case for the overall benefits of statins, but he wants more acknowledgment of the trials’ limitations.

And in a BMJ blog, Richard Lehman, retired GP and Senior advisory fellow in primary care at Cochrane UK, says that adverse effects are much more common than the trials suggest.

In July 2014, an expert panel convened by The BMJ called for anonymised individual patient data from the clinical trials of statins to be made available for independent scrutiny. Of particular interest was the extent of benefit from statins to people at low risk of heart disease, and whether the harms of statins have been characterised adequately in the trials.

In August 2014, The BMJ committed to clarifying who has access to the patient level data and how these data might be made available for independent analysis.

In a subsequent linked editorial, published in July 2015, Parish et al discuss how successful that inquiry has been thus far.

In summary; in August 2014 The BMJ’s editor in chief, Fiona Godlee, wrote to Rory Collins (for the Cholesterol Treatment Trials (CTT) Collaboration), asking him to clarify which data from the statin trials CTT has access to. The reply from Collins and colleagues confirms that CTT's access has been limited to patient level data on cause specific mortality, major vascular events, and site specific cancers. The collaboration had not analysed data on other adverse events as these were not part of the original CTT agreement. Collins and colleagues explained, however, that the trialists agreed in 2013 to pool and analyse data on all adverse events.

Godlee also wrote to the Cochrane review group on statins, asking whether it would be seeking access to the patient level data for its next update. The response from Mark Huffman and colleagues does not confirm this.

The BMJ has also written to the principal investigators of the trials included in the CTT analysis, asking them whether they have the patient level data and under what circumstances they would be willing to share them. The BMJ's letter and the replies as we have received them are posted below, as is a record of the status and nature of responses for each trial.

To date (June 2016) eight researchers have responded. All said they were potentially willing to share their data with other researchers. Members of the journal’s expert advisory group (detailed below) are now contacting authors of 183 statins trials, with the aim of characterising adverse outcomes from both published and unpublished information.

This is a substantial undertaking, in which The BMJ is grateful for guidance from its advisers. In the interests of transparency, the minutes of our discussions, and competing interests forms for each panel member, are publicly available.

We welcome comments and ideas from readers via rapid responses.

The advisory panel

  • Peter Doshi, assistant professor at the University of Maryland, and associate editor at The BMJ ;
  • Curt Furberg, professor emeritus of public health sciences at Wake Forest University School of Medicine;
  • Fiona Godlee (chair), editor in chief of The BMJ;
  • Peter Gøtzsche, director of the Nordic Cochrane Centre;
  • Carl Heneghan, director of the Centre of Evidence Based Medicine at the University of Oxford;
  • Harlan Krumholz, director of the Yale-New Haven Hospital Center for Outcomes Research and Evaluation;
  • Klim McPherson, visiting professor of public health epidemiology at the University of Oxford;
  • Emma Parish, editorial registrar at The BMJ; and
  • Huseyin Naci, assistant professor of health policy, London School of Economics and Political Science, London (joined 6 March 2015)

The trials

† These trials have been included in CTT meta-analysis (either first cycle or second cycle). Outcome data shared with the CTT on individual patients are limited to cause specific mortality, major vascular events, and site specific cancers.

Admin

Minutes of the meetings held by the advisory panel.