PLoS ONE retracts paper on treatment of tissue disease for lack of ethical approval, erroneous data
PLOS ONE has retracted an article it published earlier this year by a group from Australia who failed to receive adequate ethics approval for their study.
The paper, “Late Complications of Clinical Clostridium Histolyticum Collagenase Use in Dupuytren’s Disease,” came from Warren M. Rozen, Yasith Edirisinghe and John Crock (sorry, irony machine not working today). Dupuytren’s causes thickening of the fascia in the hands and often requires surgery. In 2011 the FDA approved a treatment for the ailment that involves injections of an enzyme — Clostridium Histolyticum Collagenase, or CHC — into the affected area.
The Aussie article looked at the effects of CHC injections in 12 patients over one year, finding that two of the patients suffered
debilitating pain and triggering requiring surgical intervention. Extensive deep-tissue scarring and adhesions were identified, providing the first visual and qualitative analysis of the pathologic effects of CHC.
Trouble was, the authors evidently didn’t have approval to collect the data, which came out of two previous Phase 3 studies, called CORD1 and CORD2. Here’s the relevant part from the paper:
Inclusion of patients in this study was approved by the institutional ethical committee of Southern Health and the National Health and Medical Research Council of Australia guidelines. The study complies with the Declaration of Helsinki, 1995. The subjects gave full written informed consent, and patient anonymity has been preserved. This institutional review board specifically approved this study.
A cross-sectional study was undertaken of a selected group of patients from the cohort of participants included in the phase III trials of CHC use as described in the CORD1 and CORD2 studies, comprising prospective, randomized, double-blind, placebo-controlled, multicentre trials. The cohort of patients comprised 12 patients who had all been treated at a single institution. CORD1 and CORD2 trial protocols for recruitment, consent, randomization, treatment and initial follow-up had been adhered to, and as such, the patients included were patients with Dupuyten’s disease who had fixed-flexion contractures of the metacarpophalangeal joint or proximal interphalangeal joint of 20 degrees or more in one finger, were of good health, and were able to appropriately consent.
But in a notice posted at 18:00 GMT on Nov. 5, the journal said, in effect, nuh-uh to that:
After the publication of the article, a number of concerns were identified in relation to the results and information reported in the article. The concerns are as follows:
1) One of the two patients did not receive the intervention involving an injection of Clostridium histolyticum collagenase as reported in the article.
2) The statement regarding ethical approval in the article is inaccurate. The study did not receive ethical approval. On the basis of the information reported in the article, the editors consider that the study involved the prospective collection of outcome data and as a result, approval by an ethics committee would have been required.
In the light of the concerns outlined, the authors and the editors retract this publication.
A note: When we first heard about this retraction, the notice was actually just a comment — one of two — on the article. It wasn’t marked as a retraction, nor did the abstract indicate that a retraction exists. That was fixed as we were putting the final touches on this post.
Intriguingly, that other comment, posted at 12:37 GMT on the 5th (in other words, about five and half hours before the retraction), may have played a role in the retraction. It says:
As a hand surgeon, I am concerned about these findings in 2/12 patients experiencing these adverse events.
1. Have the authors reported their findings to the government regulators in either the TGA in Australia or the FDA in the US, where the initial trials were done?
2. In which public database is this trial registered?
3. Based on these findings have the authors decided to stop the trial?
We suspect that these weren’t the first questions raised about the paper — after all, given time differences, etc. less than six hours is too quick a turnaround. The editor of the paper, Hani Awad, confirmed that the study was retracted, but referred us to PLoS ONE for more details. We’ll update this post if we find out more.