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Policies on Conflicts of Interest in Health Care Guideline Development: A Cross-Sectional Analysis

  • Cristina Morciano ,

    cristina.morciano@iss.it

    Affiliation Centro Nazionale Malattie Rare, Istituto Superiore di Sanità, Rome, Italy

  • Vittorio Basevi,

    Affiliation Centro di Documentazione sulla Salute Perinatale e Riproduttiva, Servizio assistenza distrettuale, medicina generale, pianificazione e sviluppo dei servizi sanitari, Regione Emilia-Romagna, Bologna, Italy

  • Carla Faralli,

    Affiliation Servizio Informatico, Documentazione, Biblioteca e Attività Editoriali, Istituto Superiore di Sanità, Rome, Italy

  • Michele Hilton Boon,

    Affiliation MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Glasgow, United Kingdom

  • Sabina Tonon,

    Affiliation Formerly Centro Nazionale Malattie Rare, Istituto Superiore di Sanità, Rome, Italy

  • Domenica Taruscio

    Affiliation Centro Nazionale Malattie Rare, Istituto Superiore di Sanità, Rome, Italy

Policies on Conflicts of Interest in Health Care Guideline Development: A Cross-Sectional Analysis

  • Cristina Morciano, 
  • Vittorio Basevi, 
  • Carla Faralli, 
  • Michele Hilton Boon, 
  • Sabina Tonon, 
  • Domenica Taruscio
PLOS
x

Abstract

Objective

To assess whether organisations that develop health care guidelines have conflict of interest (COI) policies and to review the content of the available COI policies.

Methods

Survey and content analysis of COI policies available in English, French, Spanish, and Italian conducted between September 2014 and June 2015. A 24-item data abstraction instrument was created on the basis of guideline development standards.

Results

The survey identified 29 organisations from 19 countries that met the inclusion criteria. From these organisations, 19 policies were eligible for inclusion in the content analysis. Over one-third of the policies (7/19, 37%) did not report or did not clearly report whether disclosure was a prerequisite for membership of the guideline panel. Strategies for the prevention of COI such as divestment were mentioned by only two organisations. Only 21% of policies (4/19) used criteria to determine whether an interest constitutes a COI and to assess the severity of the risk imposed.

Conclusions

The finding that some organisations, in contradiction of widely available standards, still do not have COI policies publicly available is concerning. Also troubling were the findings that some policies did not clearly report critical steps in obtaining, managing and communicating disclosure of relationships of interest. This in addition to the variability encountered in content and accessibility of COI policies may cause confusion and distrust among guideline users. It is in the interest of guideline users and developers to design an agreed-upon, comprehensive, clear, and accessible COI policy.

Introduction

The problem of conflict of interest (COI) in health care guidelines has received growing attention from health care guideline developers and users in recent years. Inadequate management of COI can result in bias and have important implications for public confidence in both the guidelines and the organisations that produce them [15]. In response to this problem, numerous recommendations for improving the identification and management of COI in guideline development have been issued [612]. The U.S. Institute of Medicine (IOM) and Guidelines International Network (G-I-N), a global network of individuals and organisations interested in guidelines [www.g-i-n.net/about-g-i-n], have both produced standards for creating trustworthy guidelines [1316] which include guiding principles to identify and manage COI. The importance of recording and addressing COI is also reflected in the appraisal criteria of AGREE II [17], an international tool for assessing the quality and reporting of health care guidelines.

Research on COI in guidelines has focused mainly on compliance with IOM and AGREE II standards [1821] as well as on the prevalence of COI among members of guideline development groups [20,2229]. Findings suggest that adherence to these standards is poor [1821] and COI are both common [19,20,23,2529] and rarely disclosed [23,26,27,29].

For guideline developers, a first step in addressing COI is to have relevant policies and procedures in place. To our knowledge only one previous study [30] has surveyed and examined the content of the COI policies of guideline developers. This cross-sectional study of 37 organisations producing a ‘large’ number of guidelines (defined as five or more guidelines listed in the National Guidelines Clearinghouse in 2009–2010) compared COI policies to IOM standards. Only 17 (17/37, 46%) of the guideline developers studied had a COI policy for guidelines in place and not one policy adhered to all 7 relevant IOM standards [14]. The study was limited to English-language guideline developers and nearly two-thirds of these organisations (24/37, 65%) were in the United States, with the remainder representing four other countries: Canada (5), the United Kingdom (5), New Zealand (2), and the Netherlands (1).

This study expands upon previous research to examine the COI policies of an international sample that includes non-English-language guideline developers.

Objectives

The aim of our study was to assess whether and how organisations address COI issues related to guideline development, and to identify and quantify problematic areas of underreporting.

We set out to capture a cross-sectional sample of worldwide guideline development organisations and to examine the content of their policies on COI available in English, French, Spanish and Italian through a predefined data abstraction instrument.

Methods

Selection of guideline development organisations

Between September 2014 and June 2015 we conducted an Internet search and content analysis of the COI policies of organisations who have a programme of health care guideline development covering a wide range of health topics i.e. a programme not limited to a particular disease or condition or to group or subgroup of diseases or conditions.

We obtained a preliminary list of 53 organisations by searching in the G-I-N database (http://www.g-i-n.net/membership/members-around-the-world) filtered by “activities” and “guideline development” (accessed September 25, 2014).

This list was integrated with a list of organisations obtained through an evidence inventory [31] of surveys of guideline developer organisations. We performed the evidence inventory to list what surveys were available on guideline developer organisations. Studies were sought from MEDLINE (1 January 2009 to 1 August 2014) and limited to English language (S1 Table). The search identified 217 articles. One author (CM) screened the titles and abstracts of all retrieved articles. A survey of European guideline developers was found and included [32] with one companion report [33]. We also included an article [34] which listed guideline handbooks/manuals to identify further guideline developers.

From these studies 60 additional organisations were identified, of which 21 were duplicates, leaving a sample of 92 organisations (S2 Table). In order to identify a manageable subsample of organisations that had the potential to produce guidelines with the most wide-ranging impacts on health, we pragmatically restricted our sample further to exclude organisations whose guideline programmes are limited to single disease areas or single health professions.

Identification of COI policies

We searched the websites of included organisations for documents that described the guideline development process (manuals, handbooks, methodology articles, webpages), disclosure of relationships of interest (DOI) forms, and any other available documents that mentioned COI issues related to guideline development and available in English, French, Italian or Spanish, with no date restrictions. We did not contact organisations directly to obtain additional information, but used only information publicly available.

We aimed to include documents that addressed COI in guideline development and that provided data for at least two of the items included in each of the following overarching items of the data abstraction instrument: “Information required for disclosure of financial and nonfinancial relationships” and “Procedures for collecting, reviewing disclosure of relationships of interest and managing conflict of interest” (Table 1). We called a document meeting these criteria a “COI policy”. In the content analysis we distinguished the term “relationship (financial and nonfinancial) of interest” and “conflict of interest”. The term “relationship of interest” refers to any interest or activity requested to be declared that may be judged to constitute a COI. Consequently we used the term “disclosure of relationships of interest” to indicate the step that precedes the review of DOI.

Data extraction and analysis

We developed a 24-item data abstraction instrument (Table 1) based on recommendations and standards of COI proposed by the IOM [13,14] and G-I-N [15]. The types of financial relationships and nonfinancial relationships considered in this study were based on those listed by IOM [13,14] and G-I-N [15].

One author (CM) abstracted information on each organisation and each COI policy into the predefined template and those data were checked by a second author (CF, ST). When there was disagreement regarding the content of a particular COI policy this was resolved by discussion. If the policy was updated during the period of data collection, we updated the abstracted information. Where disclosure forms were publicly available, data from these were integrated with the data extracted from the policies. Where inconsistencies were found, the information in the policy prevailed.

Results

Twenty-six organisations were excluded from the 92 identified as their remit was restricted to single disease specialties or single professional groups (S2 Table). Of the 66 remaining organisations, 11 were subsequently excluded because they did not provide documents on guideline development in English, French, Italian, or Spanish; 15 because they did not provide publicly accessible documents on guideline development or COI issue guideline related; 5 because their website was not found or not accessible and 6 because they were not guideline developers.

The documents of the remaining 29 organisations (Table 2) were assessed for the presence of a COI policy according to our definition. Of these organisations 21 were governmental, 4 were not for profit and 4 were professional associations. Ten organisations (10/29, 34%) were excluded from content analysis for the following reasons: 8 because their documents did not mention or provided insufficient information on COI, 1 because its handbook referred to an included parent organisation’s COI policy and 1 because its handbook was superseded by the handbook of its collaborating organisation. In the end 19 COI policies were included in the content analysis from 13 countries and 1 intergovernmental organisation. Fig 1 provides a description of the inclusion of organisations at each stage.

Conflict of interest policies

The 19 COI policies were accessible in various formats. Many organisations included their policy in a guideline handbook [37,41,44,45,47,63,6568] (10/19, 53%). Six organisations [48,56,57,59,61,64] (6/19, 32%) posted their COI policies on their website as a stand alone document. Three of these provided additional information about management of COI in their guideline handbook [49,58,62] with reference to the COI policy posted in the website. The remainder of the organisations included information on COI policy on a webpage as a flow chart [43] or in a methodological article posted on the organisation’s website [35,40] (Table 2).

The date of the COI policy was determined by considering the date of the document itself if published as stand alone document or of the corresponding date of the handbook/manual, methodological article, or webpage where the COI policy was included. The date of the 18 policies for which a date could be determined ranged from 2007 to 2014. Of the 18 policies 7 were published in 2014 (7/18, 39%), 5 were dated between 2011–2013 (5/18, 28%) and 6 were dated prior 2011 (6/18, 33%). Around one third of the policies (Table 3) [37,40,41,43,63,67] (6/19, 32%) did not report a definition of the term “conflict of interest” and the remaining policies provided heterogeneous definitions.

Disclosure of relationships of interest

All included policies outlined categories of financial relationships but characterization of specific types of nonfinancial relationships was lacking in some cases [39,40,43,47,63] (4/19, 21%) (Table 4). Policies varied in the categories of information that need to be disclosed and in whether or not disclosures were limited to information relevant to the content/topic of the guideline.

Concerning the item “who is required to report on relationships of interest”, all policies stated that a declaration is collected from members of the guideline development group/panel/committee but a minority [37,44,58,59,61,62,68] (5/19, 26%) detailed additional disclosures from staff involved in a standard guideline development process, for example, guideline methodologists, systematic review team, reviewers and advisors. In contrast, policies were much more likely [35,37,39,40,44,45,48,49,57,58,59,61,62,6468] (14/19, 74%) to require the disclosure of close personal relationships.

Procedures for collecting, reviewing DOI and managing COI

The majority of policies explicitly reported that DOI is requested before appointment of the members of the guideline development group [37,39,40,44,47,48,49,5759,6468] (12/19, 63%), while the remaining seven policies [35,41,43,45,55,56,6163] (7/19, 37%) did not report or were unclear as to whether this important practice was actually used (Table 5).

thumbnail
Table 5. Strategies for disclosure and management of conflict of interest and for recording and making disclosure accessible.

https://doi.org/10.1371/journal.pone.0166485.t005

Regarding the item “who reviews DOI and makes decision” of the 16 organisations reporting on this issue [35,37,39,40,44,45,4749,5559,61,62,6468] (16/19, 84%) the chair and/or the members of the guideline development group were the most cited responsible entity [35,37,44,45,47,5759,61,62,6466] (11/16, 69%). In contrast, only 2 organisations [67,68] (2/16, 13%) appeared to rely exclusively on a committee as an independent entity to review DOI and to devise a management plan across the entire guideline development process.

All organisations reported procedures for exclusion of members with conflicts but divestment was considered a requirement only by 2 organisations [39,40,57] (2/19, 11%), and prohibition of specific relationships by 3 organisations [37,39,40,67]. Only 4 policies [44,48,49,58,59,68] (4/19, 21%) specified an “assessment of risk”, defined as a procedure and criteria to assess whether a relationship of interest constitutes a COI and to evaluate the potential harm of the COI identified [13].

Procedures for recording and public disclosure of DOI

The majority of organisations reported a description of the procedures to record DOI [37,41,4345,4749,5559,61,62,64,6668] (15/19, 79%) whereas four did not address this issue [35,39,40,63,65] (4/19, 21%) (Table 5).

Of those policies that described activities to record DOI, the original completed DOI forms were reported to be publicly accessible on the website and/or in the published guideline by seven organisations [37,44,47,48,49,57,64,66] (7/15, 47%) with some exceptions. For example, one organisation stated DOI will be made public on the organisation website but”exception to this requirement will be by Chief Executive Officer in appropriate circumstances” [57].

Two organisations published in the guideline and/or website a summary of the DOI information [61,62,68] while other two [55,56,67] kept this information confidential although one of these mentioned the possibility of access upon request under state law [67].

Discussion

We found that of the 29 organisations corresponding to our eligibility criteria we were not able to identify COI policies for approximately one in four organisations (8/29, 28%). Failure of guideline developer organisations to adopt a publicly accessible COI policies related to guideline development has also been reported elsewhere in literature. For example, in the above mentioned cross-sectional study of Norris et al. [30] only 46% of the 37 surveyed organisations had a COI policy directly related to health care guidelines. These findings along with the data from our study suggest that the absence of a COI policy might be one of the reason behind the phenomenon of underreporting of COI in guidelines [23,26,27,29] as well as the observed uneven adherence to current standards on COI in guidelines [1821].

We also found that many organisations provided no or unclear information pertaining to some items of our data abstraction instrument. In our view, a particularly troubling area in which COI policies need to be improved is that of guideline panel selection and composition. More attention to this issue has been advocated to reduce of the potential for COI to create bias [10,12,28]. Nevertheless, in our investigation about one-third of the policies did not report or did not clearly report whether disclosure was a prerequisite for panel selection. Additionally, preventive strategy such as divestment [13,15] and prohibition [13] were rarely mentioned.

A second key area in which COI policies need to be improved is the management of the disclosed information, particularly regarding the practices of “the assessment of risk” which is defined as “practices and criteria used to determine if a relation of interest constitutes a COI and to assess the potential for harm of the COI identified” [13]. It is encouraging that the policies surveyed were directed at the most common relationships of interest in support of the identification of COI. However a policy for systematic and transparent management of the disclosed information was uncommon. Few organisations clearly stated what practices and criteria were used to determine whether a relation of interest constitutes a COI and to assess the potential for harm of the COI identified. The translation of the disclosed information into a decision or measures taken to limit the likelihood of undue influence of COI is a critical step. This step should be explicit and transparent to reduce the flexibility of the organisations in addressing financial and nonfinancial ties as well as to assure the ability of the informed reader to appraise the validity of decisions on COI issue.

In terms of the management and monitoring of the disclosed information IOM recommends that organisations should create a COI committee (Recommendation 3.1) [13]. In this regard we found that few organisations have felt the need or identified the necessary resources to have a dedicated infrastructure to act as a third party providing independent review of DOI and managing COI across all the phases of guideline development process.

Most organisations relied on the same group of individuals who develop the guidelines to handle the disclosed cases. This is of particular concern if considered in the context of the evidence of guideline chairs and panel members with a high proportion of conflicts [20,25]. Apart from an improved consistency in decisions taken across guidelines, in our view a “conflict of interest committee” could avoid administrative burden for the chair, co-chair and members of the guideline group and more importantly could consistently implement procedures for the monitoring and enforcement of the policies.

Furthermore our study underlines the issue of variation across policies in keeping with the findings of Norris et al. [30]. We found that the policies varied in their content, for example in the definition of COI (when provided), in the categories and details of the information required to be disclosed, in the time frame for disclosure, in establishing or not establishing a threshold, and in detailing who is required to declare a relationship of interest. Our sample included organisations from 13 countries and one intergovernmental organisation, so this variation in part probably reflects cultural, legal and administrative differences across countries as well as differences in organisational values and interests.

We noted that the policies were also variable in format and accessibility across the organisations, limiting the ability of the guideline user to obtain a clear and complete picture of the strategy to address COI throughout the guideline development process. An important finding is that less than half of the included organisations reported that the information from completed DOI forms was publicly accessible without restriction. Again, notwithstanding cultural, legal and administrative issues, the guideline user has the right to assess the completeness of the disclosure of COI as well as the consistency with which the policy is implemented.

This study contributes to the literature on the quality of guidelines by demonstrating, using an innovative sampling method and highly detailed data extraction, that COI remains an area that requires attention from guideline users and improvement from many guideline development organisations. The study confirms previous research that has drawn the same conclusions about COI from different samples of guidelines. The study also has some limitations that deserve comment.

First, organisations may have practices which are not fully reflected in the written COI policies or do have policy but not publicly available. However, we decided to rely only on information on COI policies publicly accessible on website since we consider accessibility an essential element of a transparent COI policy. As pointed out by IOM, COI policies should be comprehensible and accessible to the individuals and institutions that may be affected [13]. We recommend that the organisations that disseminate their own health care guidelines should provide public information on their strategies to identify and manage COI through an understandable and accessible policy.

Second, information about the policies and information about COI within the policies might be incomplete. We experienced several difficulties in locating COI policies from websites and in obtaining a complete and clear picture of the actual information required to be disclosed, the process of reviewing and the management of COI for the entire guideline development process. Some organisations published their COI policies as a complete self-contained document on their website, whereas others included information on identification and management of COI in their guideline methodology document. In some instances information was interspersed among diverse parts of the guideline methodological document, the disclosure of interest form and other supporting policies. Given the unstructured nature of the documents retrieved we checked as far as possible for presence of information about COI. We also encountered problems in the interpretation and coding of the information (e.g., on what should be disclosed) given that there is not an agreed taxonomy of terms relating to COI.

Third, we restricted our study to organisations that produce guidelines on a wide range of health topics and we excluded some professional organisations, which may limit the generalizability of our results. However, we would argue that our inclusion criteria would bias the sample towards organisations with greater resources for guideline development and therefore, if anything, our results would underestimate the extent of the problem of inadequate COI management. However our study has the strength of including 29 organisations from 19 different countries and one intergovernmental organisation in the sample and a content analysis of documents in four different languages. In terms of countries and languages represented, this may be a more representative sample of guideline development organisations than those obtained in other studies of COI in guidelines.

Conclusions

The finding that some organisations despite the recommendations and standards issued respectively in 2009 [13], 2011 [14] and 2012 [15] still do not have COI policies publicly available is concerning. Also troubling was the failure of many policies to clearly report on critical steps of obtaining, managing and communicating disclosure of relationships of interest. These problems in addition to the existing variation among policies may increase the scope for inconsistency in addressing COI issues; furthermore, unclear and incomplete COI policies may confuse readers, erode public confidence, and decrease trust in guidelines and the organisations that produce them. Thus, it is in the interest of guideline users and developers to promote strong adherence to the standards available on COI in conjunction with better scientific journal policies so that every guideline is completed by a harmonized, complete, understandable, and accessible COI policy.

Supporting Information

S1 Table. Search strategy for evidence inventory of surveys of guideline developer organisations.

https://doi.org/10.1371/journal.pone.0166485.s001

(DOCX)

S2 Table. List of 92 guideline developer organisations.

https://doi.org/10.1371/journal.pone.0166485.s002

(DOCX)

Author Contributions

  1. Conceptualization: CM VB.
  2. Data curation: CM CF ST.
  3. Formal analysis: CM CF ST.
  4. Funding acquisition: CM DT.
  5. Investigation: CM CF ST.
  6. Methodology: CM VB MHB.
  7. Project administration: CM.
  8. Supervision: CM.
  9. Visualization: CM CF.
  10. Writing – original draft: CM.
  11. Writing – review & editing: CM VB CF MHB DT.

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