Another Challenge to the Integrity of Clinical Research: The Blumsohn - Procter & Gamble - Sheffield University Case

The Times (UK) Higher Education Supplement (THES) reported an important case involving the integrity of clinical research. Unfortunately, it is not available online without a subscription, so I will quote where needed. The citations are at the bottom of this post. The case involves research carried out at Sheffield University on the drug risedronate (Actonel, made by Procter & Gamble Pharmaceuticals [P&G]).

In 2002, Professor Richard Eastell, of the Bone Metabolism Research Group at Sheffield University, was quizzed by a colleague after presenting a paper on a clinical trial of risedronate to the International Osteoporosis Foundation. Eastell then wrote to P&G statistician Ian Barton, "I think that to avoid criticism in the future it would be good if we could say that we had done the analyses independently." However, Mike Manhart, director of clinical development at P&G, did not agree, saying that letting the academics do an independent analysis would mean that "industry loses the opportunity to demonstrate its ability to be a true partner in scientific endeavors." Furthermore, he said the company had invested "hundreds of millions of dollars" in its drug trials data, so that giving out the data was not "something to be taken lightly."

Yet, when results of the trial were reported (Eastell R, Barton I, Hannon RA et al. Relationship of Early Changes in Bone Resorption to the Reduction in Fracture Risk With Risedronate. J Bone Mineral Research 2003; 18(6):1051-6.), the THES reported that the journal stated, "all authors had full access to the data and the analyses." Another author, Rosemary Hannon, however, denied that she saw all the data, but also noted "neither did I request access to all the data."

In 2002, the research unit signed another contract with P&G to do a another trial (the HIP trial) of risedronate. Aubrey Blumsohn, a Senior Lecturer, was the principal investigator. Eastell again asked Barton, "Could I suggest that Aubrey works with you to see how you did the analyis for the [previous] VERT trial, and then, when we have the HIP data, we could have the analyses run by you and by Aubrey so that we can say that we got the same result with independent analyses?" But Barton again replied, "we ... don't need to ask an independent person to analyse the data just to make a few people happy." Blumsohn later also tried to get access to the data, but by 2003 was not succesful.

However, in 2003, Blumsohn discovered that P&G had written three research abstracts and had submitted two to the American Society for Bone and Joint Metabolism and one to the American College of Rheumatology. In all cases, P&G had listed Blumsohn as first author, but Blumsohn had not written the abstracts. Blumsohn presented the latter abstract, but then said, "In retrospect I might have refused to present this work."

Furthermore, P&G started pushing Blumsohn to write a manuscript reporting trial results. Blumsohn again requested access to the data. But Barton once more replied that this would be a "distraction" from getting the manuscript "written and submitted before ... our competitors pip us to the post."

Blumsohn and P&G started to argue about the interpretation of what analyses were done. In 2004, Blumsohn formally complained to Eastell, "no self-respecting scientist could ever be expected to publish findings based on data to which they do not have free and full access." No paper has been published to date.

Eastell later said that Blumsohn should have taken his concerns "through the appropriate university channels." The university did not launch a formal investigation of Blumsohn's complaints. Instead, "Dr. Blumsohn is suspended from duties, facing disciplinary action for disussing concerns with the Times Higher."

In summary, this case illustrates

• a commercial clinical research sponsor which would not share raw data with or allow analyses by the academics who were ostensibly the principal investigators for the studies it sponsored;
• a commercial research sponsor which ghost-wrote research abstracts;
• a university which seems to have punished one of its faculty for complaining about the sponsor's excess control of clinical research.

Letters subsequently published in the Times Higher Education Supplement made valid points about all this.

When universities become dependent on drug company money they risk losing their fundamental commitment to the truth - Arthur Schafer, University of Manitoba

More than half a century ago, sociologist Robert Merton observed that the normative structure of science should be based on free and open exchange of knowledge. The situation of Aubrey Blumsohn and the acknowledgement that limiting academics' access to data is 'standard industry practice', illustrates the extent to which Merton's ideals have been eroded - Nancy Olivieri, University of Toronto

It is extremely troubling then that a university hides behind procedure and refuses to take a strong and principled stance in support of a researcher who demands full access to research data - Trudo Lemmons, University of Toronto

Stories about ghostwritten journal articles, hidden research data, a bullied academic and a university kowtowing to its industry funders have become depressingly familiar - Carl Elliott, University of Minnesota

Enough said.
References
Baty P. Data row sparks research debate. Times Higher Education Supplement, November 25, 2005.
Baty P. When access to data is a real bone of contention. Times Higher Education Supplement, November 25, 2005.
Letters & Opinion: Ensure integrity in industry links. Times Higher Education Supplement, December 2, 2005.