The Women Health Inititiateve 2004 Med Gen Review and Critique

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Inquiry Commodity

Promotional Tone in Reviews of Menopausal Hormone Therapy Later the Women'southward Health Initiative: An Assay of Published Articles

• Adriane Fugh-Berman,
• Christina Thruway McDonald,
• Alicia M. Bell,
• Emily Catherine Bethards,
• Anthony R. Scialli

10

• Published: March 15, 2011
• https://doi.org/10.1371/journal.pmed.1000425

Figures

Abstract

Background

Even later on the Women'south Wellness Initiative (WHI) found that the risks of menopausal hormone therapy (hormone therapy) outweighed benefit for asymptomatic women, nearly half of gynecologists in the U.s.a. connected to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of manufactures in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in manufactures on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review manufactures regarding menopausal hormone therapy and whether articles identified equally promotional were more likely to have been authored past those with conflicts of involvement with manufacturers of menopausal hormone therapy.

Methods and Findings

We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published betwixt July 2002 and June 2006. Side by side, nosotros conducted an boosted search using the names of these authors to identify other relevant manufactures. Finally, later on author names and affiliations were removed, l articles were evaluated by three readers for scientific accuracy and for tone. Scientific accurateness was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1) Acknowledgment or lack of denial of the adventure of breast cancer diagnosis associated with hormone therapy, and (two) acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the cess past each reader of whether the commodity appeared to promote hormone therapy. Analysis of inter-rater consistency establish moderate agreement for scientific accurateness (κ = 0.57) and substantial understanding for promotional tone (κ = 0.65). After discussion, readers found 86% of the articles to be scientifically accurate and 64% to be promotional in tone. Themes that were common in manufactures considered promotional included attacks on the methodology of the WHI, arguments that clinical trial results should not guide treatment for individuals, and arguments that observational studies are equally skilful as or better than randomized clinical trials for guiding clinical decisions. The promotional articles we identified likewise unsaid that the risks associated with hormone therapy have been exaggerated and that the benefits of hormone therapy have been or volition exist proven. Of the ten authors studied, eight were found to have alleged payment for speaking or consulting on behalf of menopausal hormone manufacturers or for research back up (vii of these eight were speakers or consultants). Thirty of 32 articles (90%) evaluated as promoting hormone therapy were authored by those with potential financial conflicts of interest, compared to xi of 18 articles (61%) by those without such conflicts (p = 0.0025). Articles promoting the utilise of menopausal hormone therapy were two.41 times (95% conviction interval 1.49–4.93) as likely to accept been authored past authors with conflicts of involvement as past authors without conflicts of interest. In manufactures from three authors with conflicts of interest some of the aforementioned text was repeated discussion-for-word in different articles.

Conclusion

At that place may be a connection betwixt receiving manufacture funding for speaking, consulting, or research and the publication of promotional opinion pieces on menopausal hormone therapy.

Please run across after in the article for the Editors' Summary

Commendation: Fugh-Berman A, McDonald CP, Bong AM, Bethards EC, Scialli AR (2011) Promotional Tone in Reviews of Menopausal Hormone Therapy After the Women'south Health Initiative: An Analysis of Published Articles. PLoS Med 8(3): e1000425. https://doi.org/ten.1371/journal.pmed.1000425

Academic Editor: Joel Lexchin, York University, Canada

Received: September xiv, 2009; Accepted: Feb three, 2011; Published: March 15, 2011

Copyright: © 2011 Fugh-Berman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study received no external or internal funding, and none of the authors received any funds or salary support for conducting this study.

Competing interests: Adriane Fugh-Berman directs PharmedOut (http://www.pharmedout.org/), a Georgetown University Medical Eye project that educates physicians well-nigh inappropriate pharmaceutical marketing practices. Dr. Fugh-Berman is also a paid expert witness on behalf of women who adult breast cancer while taking menopausal hormone therapy. Alicia M. Bell was the paid projection manager of PharmedOut during function of the time this written report was conducted. Christina McDonald and Emily Catherine Bethards received graduate school credit for their work on this study while they were master'due south students in Physiology at Georgetown University Medical Eye.

Abbreviations: CI, confidence interval; WHI, Women's Health Initiative

Editors' Summary

Background

Over the by three decades, menopausal hormones have been heavily promoted for preventing disease in women. Nevertheless, the Women'south Health Initiative (WHI) study—which enrolled more than 26,000 women in the US and which was published in 2004—found that estrogen-progestin and estrogen-only formulations (often prescribed to women around the age of menopause) increased the risk of stroke, deep vein thrombosis, dementia, and incontinence. Furthermore, this report found that the estrogen-progestin therapy increased rates of chest cancer. In fact, the estrogen-progestin arm of the WHI study was stopped in 2002 due to harmful findings, and the estrogen-only arm was stopped in 2004, also considering of harmful findings. In addition, the study also institute that neither therapy reduced cardiovascular chance or markedly benefited wellness-related quality of life measures.

Despite these results, two years after the results of WHI study were published, a survey of over 700 practicing gynecologists—the specialists who prescribe the majority of menopausal hormone therapies—in the US institute that most one-half did not find the findings of the WHI written report convincing and that 48% disagreed with the decision to stop the trial early. Furthermore, follow-up surveys institute similar results.

Why Was This Study Done?

Information technology is unclear why gynecologists and other physicians keep to prescribe menopausal hormone therapies despite the results of the WHI. Some academics fence that published industry-funded reviews and commentaries may be designed to convey specific, merely subtle, marketing messages and several academic analyses accept used internal manufacture documents disclosed in litigation cases. And then this study was conducted to investigate whether hormone therapy–promoting tone could exist identified in narrative review articles and if so, whether these articles were more likely to take been authored by people who had accepted funding from hormone manufacturers.

What Did the Researchers Do and Detect?

The researchers conducted a comprehensive literature search that identified 340 relevant articles published between July 2002 and June 2006—the iv years following the cessation of the estrogen-progestin arm of the women's health initiative written report. 10 authors had published iv to six manufactures, 47 authored two or three manufactures, and 371 authored one article each. The researchers focused on authors who had published four or more articles in the four-twelvemonth period nether study and, after author names and affiliations were removed, fifty articles were evaluated by three readers for scientific accuracy and for tone. After individually analyzing a batch of articles, the readers met to provide their initial assessments, to hash out them, and to reach consensus on tone and scientific accuracy. Then afterwards the papers were evaluated, each writer was identified and the researchers searched for authors' potential financial conflicts of interest, defined equally publicly disclosed information that the authors had received payment for research, speaking, or consulting on behalf of a manufacturer of menopausal hormone therapy.

Common themes in the fifty articles included arguments that clinical trial results should not guide treatment for individuals and suggestions that the risks associated with hormone therapy accept been exaggerated and that the benefits of hormone therapy have been or will exist proven. Furthermore, of the 10 authors studied, eight were found to accept received payment for research, speaking or consulting on behalf of menopause hormone manufacturers, and 30 of 32 articles evaluated as promoting hormone therapy were authored by those with potential financial conflicts of involvement. Articles promoting the apply of menopausal hormone therapy were more than twice as probable to have been written by authors with conflicts of involvement as by authors without conflicts of interest. Furthermore, Iii authors who were identified as having financial conflicts of interest were authors on articles where sections of their previously published articles were repeated give-and-take-for-discussion without commendation.

What Do These Findings Mean?

The findings of this report advise that there may be a link between receiving industry funding for speaking, consulting, or inquiry and the publication of plain promotional opinion pieces on menopausal hormone therapy. Furthermore, such publications may encourage physicians to go on prescribing these therapies to women of menopausal age. Therefore, physicians and other health care providers should interpret the content of review articles with caution. In addition, medical journals should follow the International Committee of Medical Journal Editors Uniform Requirements for Manuscripts, which require that all authors submit signed statements of their participation in authorship and full disclosure of whatever conflicts of involvement.

Introduction

About half of Usa gynecologists go along to distrust the results of the Women's Health Initiative (WHI) [1],[ii],[3], which found that risks of menopausal hormone therapy outweighed benefits in asymptomatic women. Such resistance to the findings of the largest randomized, placebo-controlled trial of menopausal hormone therapy always performed is curious.

The WHI enrolled more than 26,000 women. After more than five years of follow-up, the estrogen-progestin arm of the WHI was stopped in 2002 due to harm; the estrogen-only arm was stopped in 2004, also due to harm [4],[v]. Both therapies increased the risk of stroke, deep vein thrombosis [4],[5], dementia [6], and incontinence [seven]; estrogen-progestin therapy too increased rates of breast cancer [4]. Neither therapy reduced cardiovascular risk, and neither markedly benefited wellness-related quality of life measures [8],[ix].

Over the year after the first WHI results were announced, hormone prescriptions dropped past fourscore% [10]. Compared to 2002, the age-adjusted incidence of chest cancer diagnosis dropped 6.vii% in 2003, a finding attributed to decreased use of hormone therapy amid postmenopausal women [11],[12]. A contempo report confirmed an increased breast cancer incidence and a doubling of chest cancer-associated deaths amongst hormone users in the WHI [13].

In the US, gynecologists were more than likely than internists or family physicians to prescribe hormone therapy to asymptomatic women both before [fourteen],[15] and subsequently [sixteen],[17] the WHI. Between 1999 and 2002, ninety meg hormone therapy prescriptions were written annually [18]. In 2002, US gynecologists wrote seventy% of estrogen or estrogen-progestin prescriptions [19]. Sixteen months subsequently the WHI concluded, a survey of 705 fellows of the American Higher of Obstetricians and Gynecologists found that 49.1% of gynecologists did not find the WHI convincing and that 48.i% disagreed with the decision to end the trial [1]. Follow-upwards surveys institute similar results [2],[3].

Publications in the medical literature past manufacture-paid physicians have recently received attending [20]. Several academic analyses take used internal industry documents disclosed in litigation to document the use of messaging in publications regarding rofecoxib (Vioxx) [21], gabapentin (Neurontin) [22], and sertraline (Zoloft) [23]. Thousands of internal documents are available at the Drug Industry Document Archive (http://dida.library.ucsf.edu/). Industry-funded reviews and commentaries may be designed to convey specific, but subtle, marketing messages [24]. As a possible explanation for why so many physicians continue to support the employ of menopausal hormone therapy in asymptomatic women, we investigated whether promotional tone could be identified in narrative review manufactures regarding menopausal hormone therapy and whether manufactures identified every bit promotional were more likely to have been authored by those with conflicts of interest as determined by declared payments from hormone manufacturers.

Methods

Search Strategy

In 2006, we conducted a MEDLINE search using Ovid, limited to English linguistic communication reviews or comments published from July 2002 through June 2006 (the four years subsequently cessation of the estrogen-progestin arm of the WHI). The search terms were "estrogen replacement therapy" combined with "chest neoplasms AND menopause" or "cardiovascular affliction AND menopause"; "hormone replacement therapy" combined with "breast neoplasms AND menopause" or "cardiovascular disease AND menopause"; and "menopausal hormone therapy" combined with "breast cancer." A list of all authors was fabricated and the number of publications per author assessed. A subset of the most prolific authors was identified. One reader (CPM) assessed article titles, eliminating manufactures that did not focus on benefits and risks of combined estrogen-progestin menopausal hormone therapy since the WHI. An additional MEDLINE search was conducted using the names of these authors to identify other relevant manufactures.

Analysis of Content

Articles were obtained, and information on identifying authors and affiliations was removed, by back up staff. All manufactures were independently evaluated for scientific accuracy and for tone by three readers (CPM, ECB, AMB) who were then graduate students in physiology. We used graduate students in physiology equally readers because these individuals have the requisite knowledge to understand the technical aspects of the literature but accept no experience as wellness care providers or as the targets of pharmaceutical promotional efforts. Scientific accurateness was assessed based on whether or non the findings of the WHI were accurately reported using two criteria:

1. Acquittance or lack of denial of the risk of breast cancer diagnosis associated with menopausal hormone therapy, and
2. Acknowledgment that menopausal hormone therapy did non benefit cardiovascular affliction endpoints.

Determination of tone was based on each reader's assessment of whether the article appeared to promote hormone therapy (such articles were deemed "promotional") or non (manufactures deemed "nonpromotional" were either neutral nearly hormone therapy or argued confronting routine employ). Because no validated tools exist for assessing tone, each reader fabricated her conclusion co-ordinate to personal criteria. Readers were asked to record features of each article supporting their assessments. Assessments were discussed only at squad meetings, and readers did not otherwise communicate with each other about the articles.

The initial literature search identified 340 articles with a total of 428 authors. X authors had published four, 5, or six articles; 47 authored two or iii articles; and 371 authored 1 article each. Nosotros then excluded manufactures that focused on selective estrogen receptor modulators, androgens, specific receptors, or specific mechanisms, and other manufactures unlikely to discuss the risks and benefits of menopausal hormone therapy. Afterwards excluding these articles, 232 potentially relevant manufactures remained.

The 10 authors who had published iv to vi manufactures accounted for 47 (20%) of these articles. Nosotros chose to focus on these x authors because they contributed a fifth of the extant literature during the four-year period under report, and could be assumed to accept been widely read and thus influential. An additional literature search using these writer names identified thirteen additional relevant manufactures for a total of sixty articles for blinded evaluation by the three readers. Ten articles were later excluded by mutual understanding of all readers (ii publications were letters, three were duplicated references, 4 covered topics outside the scope of the study and did not specifically address our criteria, and one was published earlier July 2002). The remaining fifty papers, listed in Text S1, were evaluated individually by all readers. The ten authors who published iv or more manufactures in the 4-year period under study are identified in Table 1.

After individually analyzing a batch of manufactures, readers met to provide their initial assessments, to discuss them, and to come up to consensus, if possible, on scientific accuracy and tone. Disagreements that could non be resolved in discussion were resolved past bulk vote. After all articles had been evaluated individually and together past all readers, the authors were revealed and a search was performed for potential financial conflicts of involvement, defined every bit show that the authors had received payment for inquiry, speaking, or consulting on behalf of a manufacturer of menopausal hormone therapy.

Assessment of Conflicts of Involvement

Conflicts of interest were assessed by examining published declarations within MEDLINE-indexed manufactures, disclosures from the Council on Hormone Education (a Wyeth-funded group of consultants) [25]–[28], and a Google search of each author'south name combined with the term "conflict of involvement." Conflicts of interest were assessed for the fourth dimension catamenia catastrophe 30 June 2006. No evaluations of potential conflicts of interest disclosed after that appointment were attempted.

Statistical Analysis

The Fisher exact exam was used to assess the distribution of articles between conflicted and nonconflicted authors. A two-sided p-value of 0.05 or less was accepted as statistically significant. Risk ratios were estimated using the SABER programme from the Usa Centers for Affliction Control and Prevention. The kappa statistic (κ) was calculated according to the method of Brennan and Prediger [29].

Results

The bulk of articles (86%) were judged to be scientifically accurate according to our analysis. Thirty-two (64%) of the l articles were assessed as promotional.

After individual evaluation, all iii readers agreed on both scientific accurateness and tone for one-half (50%) of the manufactures. Readers were in agreement regarding scientific accuracy for 34 articles (68%) and regarding promotional tone for 39 manufactures (78%). Analysis of inter-rater consistency constitute moderate understanding for scientific accuracy (κ = 0.57) and substantial agreement for promotional tone (κ = 0.65). After the consensus discussions, at that place was agreement regarding scientific accuracy for 49 articles (98%) and regarding promotional tone for 48 (96%) manufactures. Overall, readers were in 94% agreement prior to unmasking the identity of the authors.

Themes in Promotional Manufactures

Readers identified themes mutual among promotional manufactures. These themes included:

• The WHI was flawed.
• The WHI was a controversial trial.
• The population studied in the WHI was inappropriate or was not representative of the general population of menopausal women.
• Clinical trial results should non guide treatment for individuals.
• Observational studies are equally skilful as or better than randomized clinical trials.
• Beast studies can guide clinical decision-making.
• The risks associated with hormone therapy have been exaggerated.
• The benefits of hormone therapy have been or will exist proven; contempo studies are an aberration.

For examples of statements representative of the themes identified, encounter Table two. Examples of what were considered promotional and nonpromotional treatments of similar topics are given in Table 3.

Articles evaluated as promotional often differed from nonpromotional articles in the way that risks were presented. For instance, most articles conceded that hormone therapy was associated with breast cancer, but promotional articles contained statements such as "The risk of breast cancer with hormonal therapy is put into perspective with the realization that this take a chance is related to hormonal dose and duration of use, and that the absolute risk remains small-scale" (reference A14 in Text S1), or "The WHI agreed with convincing prove in the literature that postmenopausal hormone therapy does not increase the adventure of breast cancer beyond that already associated with recognized risk factors, such as a positive family history" (A10 in Text S1). A nonpromotional article stated "Although estrogen and/or progestin effectively reduce vasomotor symptoms, a recent WHI randomized trial identified an unfavorable hazard/do good residuum on life-threatening diseases, including increased breast cancer, for combined estrogen plus progestin use in otherwise healthy post-menopausal women" (A40 in Text S1). Encounter Tabular array 3 for more examples of statements that minimize risks.

Reuse of Previously Published Text

Our analysis besides found, incidentally, that three authors we identified as having financial conflicts of interest were authors on manufactures where sections of their previously published articles were repeated word-for-word. Neither of the authors without declared conflicts of interest were noted to have reused text in the articles analyzed.

Eighty-four pct of the text and all seven tables in ane article (A9 in Text S1) were found in 4 other manufactures by Leon Speroff (A8, A10, A30, and A50 in Text S1). Seventy-three percent of the text and seven of ten tables from one of these articles (A10 in Text S1) were institute in iii other articles by this author (A9, A30, and A50 in Text S1). More than half (55%) of the text of one article (A8 in Text S1), published in Maturitas, was reused in the same journal a yr later (A9 in Text S1). No acquittance of earlier publication was made.

Twenty-v percent of an commodity coauthored by Susan R. Davis was reused (A25 in Text S1) in some other commodity coauthored by the same writer, without acknowledgment of before publication (A26 in Text S1). Both articles included boosted authors and we could non determine which authors were responsible for the reuse. Over two-thirds (71%) of the text of an article by Rogerio A. Lobo (A33 in Text S1), as well as its two figures and table, were reused (A14 in Text S1); in this case, adaptation, simply not republication, was acknowledged (A14 in Text S1).

Conflicts of Interest

Of the ten authors in our sample, viii were institute to have received payment for research, speaking, or consulting on behalf of menopause hormone manufacturers (Table 1). About half of the manufactures analyzed had coauthors in addition to the ten authors nosotros assessed, but we did not examine whether there were potential financial conflicts of involvement for these coauthors.

The assessments of scientific accuracy and promotional tone later on the consensus give-and-take are summarized in Table 1 co-ordinate to author's potential disharmonize of interest. 30 of 32 articles (xc%) evaluated as promoting hormone therapy were authored past those with conflicts of interest compared to 11 of 18 articles (61%) by those without conflicts of interest. The difference was meaning (p = 0.0025). Two of nine articles (22%) past authors without known conflicts were considered promotional, and 30 of 41 manufactures (73%) by authors with known conflicts were considered promotional. Articles promoting the employ of menopausal hormone therapy were 2.41 times (95% CI i.49–iv.93) more probable to have been written by authors with conflicts of interest than past authors without conflicts of interest.

Discussion

This study evaluated the relationship between the receipt by authors of payment from industry for speaking or consulting and authorship of manufactures considered to be scientifically in fault or promotional in tone. Nosotros identified an association of review articles promoting the use of hormone therapy with authors with declared financial conflicts of interest. Scientific accuracy did not appear to be afflicted by author conflicts of interest.

The effect of manufacture funding on results in clinical trials [30], meta-analyses [31],[32], clinical practise guidelines [33], and pay-for-performance quality measures [34] has been well documented. Two publications have documented scientifically unsupportable statements on the risks and benefits of menopausal hormone therapy in the medical literature [19],[35]; many of these statements appeared in reviews, commentaries, editorials, and letters.

We assessed scientific accuracy based on whether or not two findings of the WHI were accurately reported: (1) There is no proven cardioprotective issue of estrogen-progestin therapy in menopausal women or in ten-year age subgroups of menopausal women, and (2) chest cancer is diagnosed more frequently in menopausal women receiving estrogen-progestin therapy [4],[36]. Promotional tone was evaluated without formal criteria, but the readers were asked to place elements of the articles that conveyed a promotional tone. Readers evaluated articles masked every bit to the identity or affiliations of the authors. Prior to discussion, at that place was substantial understanding among the individual readers for promotional tone, and moderate agreement on scientific accuracy. After discussion, but prior to unmasking of author identities, there was consensus on both measures for all but two of the 50 papers evaluated.

We found that articles with a promotional tone were more probable to take been written by authors who had disclosed financial conflicts of involvement than by authors without such disclosures. These conflicts were determined through publicly available declarations of conflicts of involvement and may not be accurate or complete. It is possible, for example, that authors whom we identified as having no potential conflicts had undeclared conflicts or developed conflicts after the menstruation nosotros examined. One author, Nanette Wenger, for whom we identified no potential conflicts with hormone manufacturers during our report, later declared potential conflicts [37].

Our sample size of x authors was small, although the authors assessed had written one out of five of the articles identified in our search. The prevalence of financial conflicts amid authors in general is unknown, and our findings may not reverberate the universe of authors. It is possible that an cess that included less prolific authors would come up to a different conclusion.

Nearly all manufactures were evaluated as scientifically accurate regarding the event of hormones on breast cancer diagnosis and cardiovascular risk, but readers found phrasing that minimized the run a risk of chest cancer or seemed to encourage reliance upon animal studies, observational studies, or expert recommendations rather than on randomized controlled trials. Our results support an in-depth interview written report that found that physicians at two health plans commonly believed that WHI "was not applicative to the full range of patients seen in clinical practice" and "created uncertainty virtually the risks and benefits of HT" [38].

Our results suggest that authors who have received payments from industry convey more enthusiasm nigh the industry's products than do authors who have non alleged that they received such payments. These results support the findings of a study that examined conflicts of interest in reviews (amidst other publications) and found that articles past authors with potential financial conflicts of interest were more likely to support the use of a specific class of drug therapy [39]. The question of whether positive feelings about hormone therapy preceded payments from manufacture and were perhaps a basis for selection of these physicians as speakers and consultants or whether pick as a speaker or consultant led to more than positive feelings almost hormone therapy is an issue that should be explored in farther research.

Our findings also support an analysis by Tatsioni and colleagues of "partisan editorializing articles on HRT" in the Thomson ISI database by v editorialists who had written at least 12 commentaries in medical journals between 2002 and 2008 [forty]. All five had financial relationships with hormone manufacturers; these relationships were reported in only 6 of the 110 manufactures analyzed. Although there is no overlap in the author list betwixt the Tatsioni analysis and ours, Tatsioni and colleagues identified like themes, noting that mutual arguments included "HRT is effective for menopausal and related symptoms"; "Discussion of preclinical data that showed favorable effects for HRT"; "Statements challenging/criticizing unfavorable studies" (peculiarly confronting the WHI and the Million Women Study); and "Statements that HRT may subtract life-threatening and other serious outcomes." Additionally, Tatsioni et al. note that text was sometimes repeated verbatim in several articles; examples are provided in their online supplemental materials [40].

A scientist who consults for the pharmaceutical industry has described the process by which companies formulate key marketing messages into a production narrative to impact the discourse of medicine and ultimately medical knowledge [41]. Although promotional linguistic and rhetorical strategies take been identified in television commercials for prescription drugs [42], there is a dearth of academic articles on the use of rhetoric and persuasion in medical journal articles. To our knowledge, the written report by Tatsioni et al. and our report are the offset to endeavour to assess tone in review articles published in medical journals.

The extent of text reuse we identified was surprising. Tatsioni et al. documented different examples of text repeated verbatim in articles on menopausal hormone therapy, raising the question of how many more articles in the medical literature contain previously published passages. An editorial in The Lancet noted that text recycling in review textile could be viewed as "less of a crime" than "cocky-plagiarism" of original inquiry, only that the exercise "constitutes intellectual laziness at best" and is unacceptable [43].

Limitations

The methodology used to evaluate promotional tone for this study has non been previously validated. Our evaluators were not physicians and information technology is possible that the employ of physician evaluators would have yielded different results.

It is possible that the authors for whom no conflicts of interest were found actually did have conflicts of interest, either because we failed to place a disharmonize or because a conflict was not disclosed. Misclassification of conflicted authors would exist expected to bias the study results toward the zilch and is unlikely to exist responsible for the difference in tone that nosotros identified.

We cannot be certain that the x authors nosotros evaluated were representative of the universe of authors writing review articles on hormone therapy during the study period. We selected these authors because they were responsible for 20% of the relevant literature during the time period, only a report of authors with fewer publications during the flow may accept revealed different results. We also did non appraise possible conflicts of interest of coauthors or the contribution these coauthors may have made to the accuracy or tone of the articles nosotros assessed.

The assessment of multiple articles past each author may innovate an overcounting trouble in the statistical analysis inasmuch every bit each author'southward perspective might exist expected to stay the aforementioned. However, as can exist seen in Table 1, about a quarter of manufactures by authors with potential financial conflicts of involvement were accounted nonpromotional, and about a quarter of articles by those without potential financial conflicts of interest were deemed promotional.

Documents recently disclosed in litigation confronting manufacturers of hormone therapy revealed that dozens of articles ghostwritten by industry were published in the medical literature [44],[45]. The names of two of the authors whose work we assessed, Rogerio Lobo and Leon Speroff, were on the bylines of some of the reportedly ghostwritten articles [45]–[55]. We could not determine whether or non any of the articles assessed in our study were ghostwritten.

Conclusion

Our study found that narrative review articles on hormone therapy may provide accurate statements about the risks of a therapy while simultaneously providing positive impressions of that therapy for uses unsupported by show. There may exist a connection between industry funding for enquiry, speaking, or consulting and the publication of promotional pieces on menopausal hormone therapy. Health care providers should exercise caution if they choose to read such articles. We believe that medical journals should follow the International Commission of Medical Journal Editors Uniform Requirements for Manuscripts (http://www.icmje.org/urm_main.html), which crave that all authors submit signed statements of their participation in authorship and full disclosure of any conflicts of interest. In club to forestall the bloating of journals with pages of "recycled" text, medical journals should consider using antiplagiarism software.

Supporting Information

Acknowledgments

Nosotros thank Merrill Goozner for advice on written report design and obtaining disharmonize of interest information. We as well thank Cindy Pearson for helpful comments on the manuscript and Judy Davis for authoritative support.

Writer Contributions

ICMJE criteria for authorship read and met: AFB CPM AMB ECB ARS. Agree with the manuscript's results and conclusions: AFB CPM AMB ECB ARS. Designed the experiments/the study: AFB CPM ECB ARS. Analyzed the data: AFB AMB ECB ARS. Nerveless information/did experiments for the written report: CPM AMB ECB. Wrote the first typhoon of the paper: AFB. Contributed to the writing of the paper: CPM AMB ECB ARS.

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