Evidence of conflicts of interest in Medicine

Evidencia sobre conflictos de intereses en medicina

Patient care, medical research, and continuing health education should be transparent processes, but this is not usually the case. It is common for physicians to receive gifts from a pharmaceutical laboratory and then prescribe the product of the company that acts as a benefactor. In this regard, some authors have reported that simple gifts, such as a meal, have led physicians to change the prescription of medicines to a particular brand.^1-3 In the case of research, scientists may be inclined to avoid publishing results that are unfavorable to the product that is funding the study. ⁴

It is also common for medical societies to finance congresses with contributions from the pharmaceutical and medical technology industry. This financial support is invested not only in logistics, but in travel allowances, accommodation, and food for both speakers and attendees; this support may even go as far as sponsoring conferences as a clearly established marketing plan. This situation may also influence the presentation of outcomes that favor the sponsors.

These examples give an account of how doctors are being used as marketing agents.⁵ This may constitute a conflict of interest that can be understood as a situation where a judgment or action, which should be determined by a primary value established for professional or ethical reasons (protection of research subjects, obtaining safe knowledge and adequate care for the patient in the case of health), may be influenced or appear biased to obtain a secondary benefit.⁶

In Colombia, Article 106 of Act 1438 of 2011⁷ - amended through Article 133 of Act 1474 of 2011⁸ and Article 17 of Act 1751 of 2015-⁹ prohibits pharmaceutical companies that produce drugs and medical supplies from granting perks or gifts to professionals working in the health sector. Also, in 2018, the Ministry of Health and Social Promotion issued Resolution 2881, which requires pharmaceutical companies to report payments to any actor involved in the system.¹⁰

Systematic reviews are a type of scientific investigation that uses primary original studies as their unit of analysis to answer a formulated research question utilizing a systematic and explicit process of analysis of said original studies. Meta-analyses, on the other hand, are reviews that use statistical methods to combine the results of two or more studies. ^11-13

With this in mind, an analysis of the systematic reviews and meta-analyses on conflicts of interest in medicine currently available was performed to synthesize information in this regard.

A search for studies on conflicts of interest in medicine published in serialized scientific journals available in MEDLINE and LILACS was done. In MEDLINE, the search was conducted on February 10, 2018, using the MeSH term "conflict of interest" and the filters "Meta-Analysis" and "Systematic Review." In turn, the search in LILACS was conducted on February 18, 2018, using the DeCS term "Conflicto de interés" (Spanish for conflict of interest) and the filter "Systematic Review." There were no language or publication date restrictions.

First, to determine whether the studies met the inclusion criteria (being a systematic review or a meta-analysis assessing conflicts of interest in some medical area), two reviewers independently scanned the title and abstract of the publications found in the initial search. The full texts of the selected publications were then analyzed by the author of this study to obtain the final sample for the review.

The publications selected during the search for analyses were grouped according to the main activity evaluated: research articles (reviews not involving direct clinical interaction), clinical practice guidelines (CPG), reviews based on clinical practice (evaluation of medical or surgical treatments), and patient-oriented publications.

The search yielded 2 025 references in MEDLINE and 11 in LILACS, of which 29 were selected due to their relevance and design; all were taken from the MEDLINE database (Figure 1). The selected publications were grouped according to the activity evaluated (Tables 1, 2, 3 and 4).

Figure 1
Selection process of articles for analysis.
Source: Own elaboration.

Table 1
Systematic reviews and meta-analyses on conflict of interest in research articles.

Table 2
Systematic reviews of conflict of interest in clinical practice guidelines.

Table 3
Systematic reviews on conflict of interest in reviews based on clinical practice.

Table 4
Systematic reviews and meta-analyses on conflict of interest in patient-oriented research.

Conflicts of interest can occur in any professional activity.⁴³ In medicine, for example, one of the areas in which conflict of interest and outcome bias can have the greatest impact is research, because the results of a biased study can put a large number of people at risk.⁴⁴

Even though there are different methodological procedures to reduce conflicts of interest (e.g. Cochrane's), these strategies focus on study design and development rather than on funding sources.⁴⁴ This is a serious problem since many researches around the globe are financed by the industry; in fact, this is the most common source of funding in the USA.⁴⁵

Some of the analyzed systematic reviews and meta-analyses report a tendency to favor the sponsoring entity.^15-17,19 For instance, Bekelman et al.¹⁵ found that clinical trials funded by the drug manufacturer or in which the researchers have financial relationships with the manufacturers are 3.6 times more likely to report that the drug tested is effective compared to studies without such relationships.

There is also a low level of disclosure of conflicts of interest in CPGs, as the groups that develop them often do not make public their policies on the subject, their sources of funding for the development of guidelines, or the financial relationships of the members of the drafting panel. This lack of transparency makes it difficult for readers and users of the guidelines to assess undue influence and bias and, according to several studies, numerous conflicts of interest are evident when information is disseminated.^23-27 However, it is necessary to highlight the effort made by some groups or entities developing CPGs to reduce the possibility of developers having conflicts of interest. This is an effort in which transparency (understood as a way of operating so that the public can see clearly what actions are carried out) and accessibility have been cited as the most important aspects to assess conflict of interest policies in health organizations.⁴⁶

The conclusions of the clinical practice-based reviews presented in Table 3 showed that most found an association between the sponsored product and favorable research outcomes. Thus, in the review by Riaz et al.,³⁶ the declaration of financial conflicts of interest by at least one investigator was associated with a significantly higher probability of favorable outcomes for the drug or intervention under investigation (p<0.005). On the other hand, DeGeorge et al.³³ found that studies that report conflict of interest are more likely to show a favorable outcome regarding infections (p<0.01), wound complications (p<0.01), overall morbidity (p<0.07) and mortality (p<0.05).³³

Finally, the review by Fadlallah et al.⁴¹ showed that patients and the general public care very little about the personal gifts their physicians receive from the pharmaceutical industry, and that when studies focus on surgeons, patients believe that professionals decide what is best for their health, regardless of their financial relationship with the industry.

Relationships between physicians and the industry are common and vary according to the specialty, type of practice and professional activity.⁴⁷ In the USA, of 850 000 active physicians, 616 567 received some type of payment in 2015⁴⁸ (average payment per physician: USD 3 242; median payment per physician: $157); of these, 589 042 received food and drinks,¹ which was associated with a greater tendency to prescribe brand name drugs, even when there are equally effective generic drugs.^48-53

In all medical activities, it is important to establish policies that reduce the influence of secondary interests, clearly communicate the financial link with the industry, prohibit the acceptance of gifts or entertainment, and seek alternatives to industry funding of continuing medical education activities.^54,55 Careful policy setting regarding conflicts of interest helps maintain confidence in academics.⁵⁶

The relationship between the industry and researchers has been the subject of intense debate worldwide. Such is the case of the organization Cochrane, a very respected organization in the academic field, and the studies on the effectiveness and safety of the human papillomavirus vaccine, which have been at the center of controversy due to the quality of the review conducted by Arbyn et. al,⁵⁷ the sponsorship of these studies,⁵⁸ and the existing conflict of interests of the reviewers.⁵⁹

The main limitation of the present review is that the search was conducted only in two databases, had broad inclusion criteria and its findings were descriptive.

There are relationships between the pharmaceutical industry and physicians that can affect professional practice since interests, different from clinical research, may arise.

The publications analyzed in this review showed that the original studies included in the systematic reviews and meta-analyses do not always report conflicts of interest. However, when they are mentioned, the results tend to favor the sponsor's drug or device.

None stated by the author.