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Conflicts of interest in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: associations with recommendations

Abstract

Background

Treatment and diagnostic recommendations are often made in clinical guidelines, reports from advisory committee meetings, opinion pieces such as editorials, and narrative reviews. Quite often, the authors or members of advisory committees have industry ties or particular specialty interests which may impact on which interventions are recommended. Similarly, clinical guidelines and narrative reviews may be funded by industry sources resulting in conflicts of interest.

Objectives

To investigate to what degree financial and non‐financial conflicts of interest are associated with favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews.

Search methods

We searched PubMed, Embase, and the Cochrane Methodology Register for studies published up to February 2020. We also searched reference lists of included studies, Web of Science for studies citing the included studies, and grey literature sources.

Selection criteria

We included studies comparing the association between conflicts of interest and favourable recommendations of drugs or devices (e.g. recommending a particular drug) in clinical guidelines, advisory committee reports, opinion pieces, or narrative reviews.

Data collection and analysis

Two review authors independently included studies, extracted data, and assessed risk of bias. When a meta‐analysis was considered meaningful to synthesise our findings, we used random‐effects models to estimate risk ratios (RRs) with 95% confidence intervals (CIs), with RR > 1 indicating that documents (e.g. clinical guidelines) with conflicts of interest more often had favourable recommendations. We analysed associations for financial and non‐financial conflicts of interest separately, and analysed the four types of documents both separately (pre‐planned analyses) and combined (post hoc analysis).

Main results

We included 21 studies analysing 106 clinical guidelines, 1809 advisory committee reports, 340 opinion pieces, and 497 narrative reviews. We received unpublished data from 11 studies; eight full data sets and three summary data sets. Fifteen studies had a risk of confounding, as they compared documents that may differ in other aspects than conflicts of interest (e.g. documents on different drugs used for different populations). The associations between financial conflicts of interest and favourable recommendations were: clinical guidelines, RR: 1.26, 95% CI: 0.93 to 1.69 (four studies of 86 clinical guidelines); advisory committee reports, RR: 1.20, 95% CI: 0.99 to 1.45 (four studies of 629 advisory committee reports); opinion pieces, RR: 2.62, 95% CI: 0.91 to 7.55 (four studies of 284 opinion pieces); and narrative reviews, RR: 1.20, 95% CI: 0.97 to 1.49 (four studies of 457 narrative reviews). An analysis combining all four document types supported these findings (RR: 1.26, 95% CI: 1.09 to 1.44).

One study investigating specialty interests found that the association between including radiologist guideline authors and recommending routine breast cancer screening was RR: 2.10, 95% CI: 0.92 to 4.77 (12 clinical guidelines).

Authors’ conclusions

We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. However, we also stress risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non‐financial conflicts of interest impact on recommendations.

Plain language summary

Conflicts of interest and recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews

Which treatments and diagnostic tests doctors offer to their patients are often based on recommendations expressed in a variety of documents. A common example is clinical guidelines, which are statements providing recommendations on how to diagnose and treat patients on the basis of the best available evidence. The treatments that may be offered to patients are also influenced by which drugs are recommended for approval by drug advisory committees at regulatory drug agencies such as the US Food and Drug Administration (FDA). Finally, doctors may also be influenced by recommendations expressed in opinion pieces, such as editorials, or in narrative review papers in medical journals.

Quite often, publications expressing clinical recommendations are written by authors with conflicts of interest related to a specific product, for example when the author acts as a consultant for the company producing the treatment of interest. Such conflicts of interest may impact on the recommendations made. Similarly, authors may have so‐called non‐financial conflicts of interest such as belonging to a specific profession, for example being an orthopaedic surgeon, which may influence whether a specific intervention is preferred over another. This Cochrane Methodology Review investigated how financial and non‐financial conflicts of interest are associated with the recommendations made in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews.

We included 21 studies and we interpreted our findings to indicate that financial conflicts of interest are associated with favourable recommendations in these documents, although there is some uncertainty around the size of the effect. This means that when such publications are written by authors with financial conflicts of interest, they more often have favourable recommendations than publications written by authors without conflicts of interest. Only a single study investigated the impact of non‐financial conflicts of interest in clinical guidelines and the results were uncertain, but indicated a similar direction of effect.

We suggest that patients, doctors, and healthcare decision makers primarily use clinical guidelines, opinion pieces, and narrative reviews that have been written by authors without financial conflicts of interest. If that is not possible, users should read and interpret the publications with caution. Furthermore, our findings suggest that if committee members are asked to vote on the recommendation of a drug, they may be more likely to vote in favour of the drug when they have financial conflicts of interest.

Authors’ conclusions

Implication for systematic reviews and evaluations of healthcare

We interpreted our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. Although the magnitude of effect is fairly consistent across document types, most studies had a risk of confounding and our individual analyses of each document type had some degree of statistical imprecision. It is more uncertain whether non‐financial conflicts of interest impact on recommendations.

Our findings support conflicts of interest policies from major guideline issuing organisations such as the National Institute for Health and Care Excellence, the US Preventive Services Task Force, and the World Health Organization (NICE 2019U.S. Preventive Services Task Force 2018WHO 2014). These policies aim to minimise the number and role of guideline authors with conflicts of interest. Similarly, some high impact journals manage conflicts of interest beyond disclosure, for example New England Journal of Medicine prohibits narrative reviews and editorials with significant financial conflicts of interest (> US$ 10,000), and The Lancet prohibits commentaries, seminars, reviews, and series by authors with relevant stock ownership, employment, or company board membership (Bero 2018Lundh 2020). Other journals should consider introducing such polices in order to minimise the influence from conflicts of interest on journal content.

In line with this, the FDA introduced more stringent criteria on which types of conflicts of interest where allowed for committee members in 2008 (Ackerley 2009). This could be a possible explanation as to why the study by Zhang and colleagues (Zhang 2019), which exclusively sampled advisory committee reports from 2008 and onwards, found a somewhat weaker association between financial conflicts of interest and recommendations in advisory committee reports than the three other studies included in our pooled analyses (Ackerley 2009Lurie 2006Tibau 2016).

To minimise influence from conflicts of interest we suggest that patients, clinicians, and healthcare decision makers primarily use clinical guidelines that are based on rigorous methodology and have clear policies of how to manage conflicts of interest, such as excluding or minimising the role of members with conflicts and ensuring a broad skill set in the panel. If such guidelines are not available, users should interpret such guidelines with caution. Similarly, journal readers should prefer publications written by authors without conflicts of interest.

Implication for methodological research

Ideally, future studies should try to minimise the risk of confounding, e.g. by using a matched study design (Jørgensen 2006). However, identifying editorials commenting on the same study or guidelines addressing the same question and developed using similar methods might be a challenge. Furthermore, future research could focus on investigating whether specific types of financial conflicts of interest (e.g. advisory board membership) or conflicts of interest related to specific companies (e.g. drug manufacturer) have a greater impact than others. Moreover, the included studies used various definitions of financial conflicts of interest and recommendations, and use of a standardised terminology would be helpful.

Investigating the impact of non‐financial conflicts of interest is challenging because no uniform definition exists. On one hand, a multitude of interests such as specialty interests, intellectual interests, personal beliefs, and personal relationships can be viewed as non‐financial conflicts of interest (The PLoS Medicine Editors 2008Viswanathan 2014). On the other hand, labelling personal beliefs and theoretical schools of thoughts as conflicts of interest risks muddying the waters since no researcher is completely interest free or free from intellectual pre‐conceptions (Bero 2014Bero 2016Bero 2017). Furthermore, the distinction between financial and non‐financial conflicts of interest is not always clear. For example, in relation to the included study on mammography screening guidelines (Norris 2012), it can be debated whether being a radiologist should be considered a purely non‐financial conflict of interest because radiologists may have direct financial income from breast cancer screening. Future studies could focus on investigating the impact of the various types of non‐financial conflicts of interest on favourable recommendations and on the impact of managing such interests using guideline panels with a broad range of skill sets, rather than mainly content area experts.

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