Conflits d’intérêts rarement déclarés dans les méta-analyses d’essais cliniques (JAMA)

Le JAMA (Journal of the American Medical Association) publie dans son numéro du 9 mars 2011 une étude faite par des investigateurs du Canada, des Etats-Unis et des Pays-Bas, dirigée par Michelle Roseman (Université McGill, Montréal): « Reporting of conflicts of interest in meta-analyses of trials of pharmacological treatments« . JAMA. 2011;305(10):1008-17 » (Déclaration des conflits d’intérêts dans les méta-analyses d’essais cliniques de traitements pharmacologiques).

29 méta-analyses se référant à 509 essais cliniques contrôlés randomisés (RCT : randomized controlled trials) ont été retenues. Quant aux journaux, ont été retenus ceux ayant un facteur d’impact élevé : Annals of Internal Medicine, British Medical Journal, JAMA, Lancet, NEJM, PLoS Medicine ; s’y ajoute la Cochrane Collaboration (pour les revues systématiques) et plusieurs journaux de 5 spécialités différentes. Sur ces 29 méta-analyses, onze sont parues dans le JAMA, le Lancet, le BMJ et les Annals of Internal Medicine.

Seules 2 méta-analyses sur les 29 (soit 7%) comportent des déclarations d’intérêt relatives au financement des essais RCT, mais ces indications sont placées à des endroits peu visibles (notes de bas de page, tableaux…). Aucune méta-analyse ne comporte de déclaration d’intérêts des investigateurs et auteurs des essais. 318 RCT sur 509 (soit 62,5 %) déclarent les sources de financement. Il s’agit de l’industrie pharmaceutique pour 219 d’entre eux (68,9 %), partiellement ou totalement ; et de sources autres pour 30,5%. Un peu moins d’un pour cent n’ont pas de financement. Un quart des essais RCT (132 sur les 509) incluent des déclarations d’intérêts des auteurs. Sur ces 132 essais contenant des « disclosures », 41 (soit 68,9%) ont au moins un auteur en situation de conflits d’intérêts avec les pharmas.

Les auteurs suggèrent d’améliorer et actualiser les recommandations PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis), pour qu’elles insistent sur la déclaration des liens d’intérêt, de quelque nature qu’ils soient, dans toutes les méta-analyses et tous les essais RCT. Même chose pour les critères AMSTAR (assessment of multiple systematic reviews) d’évaluation des méta-analyses, afin que l’absence de déclaration soit considérée comme un biais à prendre en compte lors de l’évaluation. Les auteurs recommandent aussi à la Cochrane collaboration d’aller plus loin :

“Meta-analysts should evaluate the potential for bias due to pharmaceutical industry study funding and author-industry financial ties as part of their standard risk of bias assessment. (…)

Although some risk of bias assessment tools include a domain for study funding source, most do not.67 Currently, the Cochrane Collaboration’s Risk of Bias tool includes an optional “other sources of bias” domain,63 which meta-analysts could use to include information on COIs. We recommend that the Cochrane Collaboration consider formalizing the requirement to assess potential bias from COIs.”

Références complètes

Roseman M, Milette K, Bero LA et coll. Reporting of conflicts of interest in meta-analyses of trials of pharmacological treatments. JAMA. 2011;305(10):1008-17.

Extrait du texte complet, réservé aux abonnés (section “Résultats”)

“Study Funding and Author-Industry Financial Ties of Meta-analyses

As shown in Table 1 and Table 2, 0 of the 29 selected meta-analyses reported being funded by the pharmaceutical industry. Fourteen (48.3%) reported nonindustry funding, 4 reported no study funding (13.8%), and the funding source of 11 (37.9%) was not reported. At least 1 author of 16 of the 29 meta-analyses (55.2%) reported at least 1 financial tie to the pharmaceutical industry, all of the authors of 12 of the meta-analyses (41.4%) reported 0 financial ties to the pharmaceutical industry, and author financial ties were not reported in 1 meta-analysis (3.4%). Specific types of author ties to the pharmaceutical industry for each meta-analysis are shown in eTable 2, available at http://jama.ama-assn.org/content/305/10/1008/suppl/DC1. Only 1 of the 29 meta-analyses listed authors employed by the pharmaceutical industry.37

Study Funding and Author-Industry Financial Ties of Included RCTs

The 29 selected meta-analyses synthesized data from a total of 509 RCTs. As shown in Table 3, 62.5% (318 of 509) of included RCTs reported funding source. Of these, 68.9% (219 of 318) were funded in part or whole by the pharmaceutical industry; 30.5% (97 of 318) by nonindustry funding sources, including 28 RCTs in which a study drug was supplied by the pharmaceutical industry; and less than 1% (2 of 318) reported that the trial received no funding. Characteristics of the 509 included RCTs, including COI data, are presented in eTable 3, available at http://jama.ama-assn.org/content/305/10/1008/suppl/DC1.

Author financial disclosures were reported in only 25.9% (132 of 509) of included RCTs. Among these, 68.9% (91 of 132) reported 1 or more authors having financial ties to the pharmaceutical industry. Author affiliations were reported in 94.7% of included RCTs (482 of 509), including 26.1% (126 of 482) with at least 1 author employed by the pharmaceutical industry.

Reporting of Disclosed COIs From RCTs Included in Meta-analyses

As shown in Table 3, only 2 of the 29 selected meta-analyses reported the funding source of included RCTs.47 62 One listed RCT funding sources in a table footnote 47 and the other in the Characteristics of Studies table that followed the main document and references.62 Neither mentioned RCT funding sources in the column of a core table, in the text, or in an assessment of potential bias. Both of these meta-analyses 47 62 reported nonindustry funding for the meta-analysis. One of the meta-analyses reported no author ties to the pharmaceutical industry,62 whereas the other reported that 1 of 3 authors had a link to the pharmaceutical industry.47 None of the 29 meta-analyses reported author-industry financial ties or employment of included RCTs.

Of the 29 meta-analyses, 25 assessed quality or risk of bias in included RCTs. One of the meta-analyses that reported the funding source of included RCTs 47 used an ad hoc method to assess study quality that did not include an assessment of study funding. Five meta-analyses 34 44 60 61 62 used at least 3 of the 6 domains from the Cochrane Risk of Bias tool, which does not produce a single quality score, but rather provides ratings for individual risk components.63 Only 1 of the 5 meta-analyses 62 reported the funding source of included RCTs, but it did not include this information in the assessment of risk of bias.

In 7 of 29 meta-analyses (Table 3), 100% of included RCTs disclosed at least 1 form of COI in the original RCT publications.37 38 40 44 47 54 60 In 4 of these 7 meta-analyses,37 44 54 60 100% of included RCTs that reported study funding were funded by the pharmaceutical industry. Only 1 of the 7 meta-analyses, however, provided information on study funding of included RCTs,47 and that was done in a table footnote.

Twenty-seven of 29 meta-analysis authors provided information on data extraction protocols. Two recorded and reported RCT funding sources 47 62; 5 recorded, but did not report funding sources; and 20 did not record funding sources. Only 2 of the 27 meta-analyses recorded RCT author-industry financial ties, but neither published this information. (…)”

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Elena Pasca

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