Editor ’ s Corner
The Good Steward of Science
I
The content of the Editor ’ s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated .
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HAVE PARTICIPATED IN a number of clinical trials and database projects with pharmaceutical companies and , as a result , have been an author on a few abstracts and manuscripts with industry as a partner .
Truth be told , much of this research has been extremely rewarding , intellectually stimulating , and – most importantly – has advanced care for my patients . Academic-industry partnerships have become almost-requisite for drug development and for providing an adequate portfolio of trials for people with devastating hematologic conditions who need better therapies . The notion that we can make these advances based solely on inhouse , bench-to-bedside approaches is aspirational , logistically impractical , and , consequently , has become largely effete . This much , I suspect , industry and I can agree on . When it comes to publishing results of trials , our motivations for doing so may diverge . Though pharmaceutical companies mandate separation between their medical affairs and sales divisions , in practice , they can influence each other . I don ’ t care one whiff how a scientific publication influences units of drugs sold or supports off-label medication use . My medical affairs collaborators or in-house writers who hold stock in the company may not be so cavalier – even if subconsciously .
Several years ago , I was approached by a pharmaceutical company who knew of my interests in myeloid malignancies and working with big datasets . Their marketing team had accumulated a lot of information about U . S . physician practice patterns specific to patients with these conditions . They wondered if I would be interested in exploring their data and developing some research questions .
I nearly fell over myself replying in the affirmative . At the time , little was known about the epidemiology and “ real-world ” treatment of patients with chronic myeloid malignancies .
We quickly put into place the appropriate confidential disclosure agreement , and before long I was working with the company ’ s statistician on a near-daily basis . She was surprised when I asked to review the actual SAS ( statistical ) outputs from her analyses , but hey , some of us like to spend our weekends watching the Pittsburgh Steelers annihilate the Cleveland Browns in football , while others like to pore over 2 × 2 tables of numbers displayed in inelegant fonts .
Which is not something I would ever admit on a first date . Or on a second date . Or , really , within the first five years of marriage .
I put together an abstract , and after it went through approximately 37 layers of approval within the company ( this is hyperbole ; it was closer to 35 layers of approval ) submitted it for consideration for that year ’ s ASH annual meeting . I was thrilled to learn that it was accepted as a poster presentation and stood by the poster summarizing our research in the first week of that December .
In early September , after submitting the abstract , and while the data and their interpretation were still fresh in my mind , I wrote a draft of the manuscript and sent it to the company ’ s statistician and their medical writer to review . Within 24 hours , I received a reply , saying :
“ Wow , you put this together quickly ! [ Read : We weren ’ t quite ready for that .] A job in medical writing is available for you anytime you fancy a career change ! [ Read : We have in-house writers who could have written it for you , so stick to being a doctor .] I am working to figure out how quickly we can do this , taking into account internal resources and review times . [ Read : I ’ m going to have to run this up the flagpole and see if we can allow a renegade researcher to determine how to present these data .]” I think I even saw some of the sender ’ s sweat running in rivulets down my computer monitor .
“ Oh , I was just so excited about the findings , I couldn ’ t help myself !” I answered , only a little tongue-in-cheek . “ I don ’ t think it would take too much to finish and submit it to a journal .”
The reply back was more formal . “ Unfortunately , I don ’ t think we are going to be able to get the manuscript submitted by December . A January / February submission time is more realistic .” Over the next few months , comments from employees of the
Mikkael A . Sekeres , MD , MS , is director of the Leukemia Program at the Cleveland Clinic in Cleveland , OH .
company about the manuscript trickled in . One deleted a sentence from the discussion section in which I referenced a policy decision restricting use of a drug the company manufactured . I put it back in . Another asked for more analyses supporting use of another drug the company manufactured . I ignored it .
Conference calls were requested . I participated . Further manuscript edits and suggestions came . I maintained my equipoise . In all , the paper went through 12 iterations . This is not hyperbole ; Manuscript . v . 12 was the document name of the final version submitted to a journal . When it was accepted , I could proudly hold it up as a successful collaboration with industry that was balanced in its reporting and discussion of results . But it took a heck of a lot of mettle to get there . Spin can be subtle , but influential . How many times have we read introduction sections to early-phase study publications that provide low estimates of response rates to established therapies , setting the reader up to be impressed with the moderate response rate observed with the drug being studied ? Or that claim an “ unmet medical need ” for a drug , when really the only unmet need is for the drug to find an indication in which it works marginally ?
Manuscripts declare drugs “ promising ” with response rates of less than 15 percent , or state a drug has “ acceptable toxicity ” even though the rates of significant adverse events or early deaths may eclipse that response rate . Discussion sections may take a detour to discuss other drugs manufactured by the same company that sponsored the trial . Conclusion sections suggest that a particular intervention represents a new “ standard of care ” for the disease in question , when “ standards ” should be declared only by the hematology / oncology community as a whole .
To avoid this spin , ideally , as clinical investigators , we should all write the first draft of any manuscript . Recognizing other demands on our time , and that not all clinical investigators deliver manuscripts efficiently ( and thus can unwittingly hold important findings captive , which may delay translation to clinical practice ), we need to be rigorous stewards of the balanced presentation and publication of trial results .
Especially when delivered by emissaries who are employed by the company that stands to benefit from those findings .
Words matter . We owe it to the scientific community , and to our patients , to make sure those words are ours .
Mikkael Sekeres , MD , MS Editor-in-Chief
8 ASH Clinical News February 2018