We have identified a substantial body of editorializing literature that has a partisan stance in favor of HRT. These articles include mostly editorials, non-systematic reviews, guidelines and consensus statements. They use a standard armamentarium of arguments to support HRT and to criticize the large studies that demonstrated problems with HRT. Similar arguments are repeated across different articles. Four journals have contributed most of the editorializing literature that we analyzed. Both the prolific editorializing authors and the professional societies publishing these journals had relationships to the pharmaceutical industry. However, only 6 of the 110 partisan articles specifically mentioned any such funding or conflicts of interest.
Experience from other fields suggests that even when large trials contradict previous beliefs about the benefits of various interventions, a section of the medical literature continues to support previous practices and raises counterarguments as to why the large studies were wrong. This “die hard” pattern has been demonstrated in vitamin E for cardiovascular prevention, beta-carotene for cancer prevention, estrogen for dementia prevention10
and percutaneous coronary intervention for stable chronic coronary artery disease11
(in the latter case, the source of resistance came primarily from interventional cardiologists).12
Moreover, the key vehicle of expressing doubts about large trials has been through editorials and expert statements. Similarly, our study documents a large literature of editorializing articles that emanate from authors and societies involved in the promotion of HRT.
Defending one’s practices is not unethical, and many of the arguments raised have some validity or may even be correct. The authors of these articles may be excellent scientists. However, it is concerning that almost none of these partisan articles reported the conflicts of interest of their authors. Obviously, the average reader would not have time to investigate the whole publication corpus of an author to determine whether he or she ever reported any conflicts of interest. Omission of conflicts of interest was prominent not only for short editorials, but also for guideline and consensus articles that were typically sponsored by these professional societies. As of January 2010, three of the four journals that hosted most of the editorializing articles clearly reported (in their instructions to authors) that authors should disclose any conflicts of interest in their manuscripts, and the fourth journal (Geburtshilfe und Frauenheilkunde) mentioned that authors should provide notes for financial or other support in a footnote at the end of the text. Given that these instructions to the authors are online, it is unclear when these policies where implemented. Reporting of conflicts is a responsibility both of the editorialists and of the journals that should ensure that transparent reporting of conflicts is actually enforced.
Most professional societies have industry ties: industry sponsors their meetings, provides awards/grants, and maintains a team of speakers from society members. Societies sponsor and publish scientific journals, and propagate practice guidelines that influence their members. This creates intricate relationships with industry,12–21
especially for societies whose core practice is related to specific products, as is the case for menopause specialists and HRT.
Pharmaceutical involvement in research may affect study design, focus and results,22–25
and authors’ published positions correlate with financial relationships with manufacturers in review articles and letters to the editor.26
There are also strong interactions between industry and authors of practice guidelines.27
Otherwise excellent scientists may be tempted to produce editorials with non-evidence-based claims. Almost all major field experts have potential financial conflicts; while it is hard to find experts without any conflicts,28
disclosure is essential.29
We built our search for eligible articles around the most prolific partisan editorialists, and this is just a selected fraction of all the editorials written on HRT. However, these authors clearly stood apart in the volume of their editorializing articles when compared with the other 3,000 authors who have written mostly sporadic editorials. Similarly, four specialty journals clearly stood apart in the volume of partisan editorializing items compared with all other journals that may have some interest in the field. The cumulative impact on clinical practice is shaped by diverse opinion leaders, both those who write numerous partisan articles and those who may write a few non-partisan ones. For HRT, most high-impact authorities have made conservative statements about its use. This includes the American Heart Association7
, the North American Menopause Society8
, the Canadian Task Force on Preventive Health Care9
and the American College of Obstetricians and Gynecologists6
(the first three of these also report conflicts of interest in their publications). The cumulative influence of these major authorities is apparently higher than that of concentrated partisan publications in journals with modest impact. Moreover, hundreds of journals published editorials on HRT, and most of them published only a few such items. Even single editorials may have a considerable impact, especially if published in high-impact journals. However, most high-impact general medical journals have very strict policies for conflicts of interest and stringent review filters. Extremely partisan positions may be more difficult to publish in editorials in such journals. Specialty journals sponsored by professional societies may thus be a more convenient publication venue for partisan editorialists.
Finally, we do not wish to make claims about the underlying motives for each article in the partisan literature. Previous studies30–33
have pointed even to guest authorship and ghostwriting practices in developing a pro-industry literature. For HRT in particular, several months ago an investigation was announced by Senator Grassley1
claiming that Wyeth and leading HRT experts were involved in ghost- and guest-authorship favoring Prempro (a combination of estrogen and progestin). Recently, the Institute of Medicine suggested that medical schools should abandon long-accepted relationships with the industry and practices that create conflicts of interest, threaten the integrity of their missions and their reputations, and jeopardize public trust.34
Nonetheless, we do not intend to blame the authors of the specific articles we examined. The mere wish to defend one’s practice, procedures and scientific beliefs may be sufficient explanation, and all the authors involved in these articles may have been fully responsible for and sincere in their writings. However, this complex background where large drug markets are at stake further highlights the need for full disclosure of conflicts of interest to promote discernment among readers and prevent mistrust.