ArticlePDF Available

Undisclosed financial ties between guideline writers and pharmaceutical companies: A cross-sectional study across 10 disease categories

Authors:

Abstract and Figures

Objectives To investigate the proportion of potentially relevant undisclosed financial ties between clinical practice guideline writers and pharmaceutical companies. Design Cross-sectional study of a stratified random sample of Australian guidelines and writers. Setting Guidelines available from Australia’s National Health and Medical Research Council guideline database, 2012–2014, stratified across 10 health priority areas. Population 402 authors of 33 guidelines, including up to four from each area, dependent on availability: arthritis/musculoskeletal (3); asthma (4); cancer (4); cardiovascular (4); diabetes (4); injury (3); kidney/urogenital (4); mental health (4); neurological (1); obesity (1). For guideline writers with no disclosures, or who disclosed no ties, a search of disclosures in the medical literature in the 5 years prior to guideline publication identified potentially relevant ties, undisclosed in guidelines. Guidelines were included if they contained recommendations of medicines, and writers included if developing or writing guidelines. Main outcome measures Proportions of guideline writers with potentially relevant undisclosed financial ties to pharmaceutical companies active in the therapeutic area; proportion of guidelines including at least one writer with a potentially relevant undisclosed tie. Results 344 of 402 writers (86%; 95% CI 82% to 89%) either had no published disclosures (228) or disclosed they had no ties (116). Of the 344 with no disclosed ties, 83 (24%; 95% CI 20% to 29%) had potentially relevant undisclosed ties. Of 33 guidelines, 23 (70%; 95% CI 51% to 84%) included at least one writer with a potentially relevant undisclosed tie. Writers of guidelines developed and funded by governments were less likely to have undisclosed financial ties (8.1%vs30.6%; risk ratio 0.26; 95% CI 0.13 to 0.53; p<0.001). Conclusions Almost one in four guideline writers with no disclosed ties may have potentially relevant undisclosed ties to pharmaceutical companies. These data confirm the need for strategies to ensure greater transparency and more independence in relationships between guidelines and industry.
Content may be subject to copyright.
1
MoynihanR, etal. BMJ Open 2019;9:e025864. doi:10.1136/bmjopen-2018-025864
Open access
Undisclosed nancial ties between
guideline writers and pharmaceutical
companies: a cross-sectional study
across 10 disease categories
Ray Moynihan,1 Alexandra Lai,2 Huw Jarvis,3 Geraint Duggan,3
Stephanie Goodrick,3 Elaine Beller,1 Lisa Bero2
To cite: MoynihanR, LaiA,
JarvisH, etal. Undisclosed
nancial ties between guideline
writers and pharmaceutical
companies: a cross-sectional
study across 10 disease
categories. BMJ Open
2019;9:e025864. doi:10.1136/
bmjopen-2018-025864
Prepublication history and
additional material for this
paper are available online. To
view these les, please visit
the journal online (http:// dx. doi.
org/ 10. 1136/ bmjopen- 2018-
025864).
Received 7 August 2018
Revised 6 November 2018
Accepted 6 November 2018
1Centre for Research in
Evidence-Based Practice,
Bond University, Gold Coast,
Queensland, Australia
2Charles Perkins Centre and
Faculty of Pharmacy, University
of Sydney, Sydney, Australia
3National Health and Medical
Research Council, Canberra,
Australian Capital Territory,
Australia
Correspondence to
RayMoynihan;
raymoynihan@ bond. edu. au
Research
© Author(s) (or their
employer(s)) 2019. Re-use
permitted under CC BY-NC. No
commercial re-use. See rights
and permissions. Published by
BMJ.
ABSTRACT
Objectives To investigate the proportion of potentially
relevant undisclosed nancial ties between clinical
practice guideline writers and pharmaceutical companies.
Design Cross-sectional study of a stratied random
sample of Australian guidelines and writers.
Setting Guidelines available from Australia’s National
Health and Medical Research Council guideline database,
2012–2014, stratied across 10 health priority areas.
Population 402 authors of 33 guidelines, including up to
four from each area, dependent on availability: arthritis/
musculoskeletal (3); asthma (4); cancer (4); cardiovascular
(4); diabetes (4); injury (3); kidney/urogenital (4); mental
health (4); neurological (1); obesity (1). For guideline
writers with no disclosures, or who disclosed no ties, a
search of disclosures in the medical literature in the 5
years prior to guideline publication identied potentially
relevant ties, undisclosed in guidelines. Guidelines were
included if they contained recommendations of medicines,
and writers included if developing or writing guidelines.
Main outcome measures Proportions of guideline writers
with potentially relevant undisclosed nancial ties to
pharmaceutical companies active in the therapeutic area;
proportion of guidelines including at least one writer with a
potentially relevant undisclosed tie.
Results 344 of 402 writers (86%; 95% CI 82% to 89%)
either had no published disclosures (228) or disclosed
they had no ties (116). Of the 344 with no disclosed ties,
83 (24%; 95% CI 20% to 29%) had potentially relevant
undisclosed ties. Of 33 guidelines, 23 (70%; 95% CI 51%
to 84%) included at least one writer with a potentially
relevant undisclosed tie. Writers of guidelines developed
and funded by governments were less likely to have
undisclosed nancial ties (8.1%vs30.6%; risk ratio 0.26;
95% CI 0.13 to 0.53; p<0.001).
Conclusions Almost one in four guideline writers with no
disclosed ties may have potentially relevant undisclosed
ties to pharmaceutical companies. These data conrm the
need for strategies to ensure greater transparency and
more independence in relationships between guidelines
and industry.
INTRODUCTION
There is global concern about the nature
and extent of financial ties between
pharmaceutical companies and health
professionals, including those who develop
influential clinical practice guidelines.1–3
In 2009, a landmark Institute of Medicine
report on conflicts of interest acknowl-
edged the importance of collaboration with
industry, but warned financial ties to industry
were widespread and risked jeopardising the
integrity of medical education, research and
practice, and called for greater transparency
and independence.1 A subsequent Institute
of Medicine report, titled ‘Clinical prac-
tice guidelines we can trust’, recommended
that groups developing guidelines ‘opti-
mally comprise members without conflict of
interest.’2 Systematic review evidence suggests
most guideline writers disclose some form of
industry affiliation, with estimates between
56% and 87%.3 There are, however, few data
on the extent of undisclosed financial ties of
guideline writers. One study of North Amer-
ican cholesterol and diabetes guidelines esti-
mated 11% of writers had undisclosed ties,4
another study of American head and neck
surgery guidelines found 6% had discrep-
ancies between disclosures and an open
payments database,5 while a Danish study
Strengths and limitations of this study
Our study is the largest to date to examine undis-
closed ties of guideline writers and includes a broad
sample of guidelines across 10 disease categories.
Our study includes guidelines with different funding
and development arrangements, enabling compari-
son of guidelines funded and developed by govern-
ment, with other guidelines.
Our study did not investigate the undisclosed ties
of guideline writers who had disclosed ties in the
sample of guidelines analysed.
Study results likely underestimate the extent of un-
disclosed nancial ties of guideline writers.
on 6 February 2019 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2018-025864 on 5 February 2019. Downloaded from
2MoynihanR, etal. BMJ Open 2019;9:e025864. doi:10.1136/bmjopen-2018-025864
Open access
of 14 specialty society guidelines found 52% had undis-
closed ties.6 (For consistency, the term guideline writer is
used throughout to refer to those who develop, draft and
author guidelines.)
A conflict of interest is defined as “a set of circum-
stances that creates a risk that professional judgement or
actions regarding a primary interest will be unduly influ-
enced by a secondary interest”.1 A primary interest of a
guideline writer may be maximising health outcomes,
and a secondary interest could be personal gain derived
from a financial relationship with a company active in
the relevant therapeutic area. Evidence from other areas,
such as clinical trials, has shown such conflicts of interest
may introduce bias. A recent systematic review found
drug trials sponsored by industry more often have effi-
cacy results and conclusions favourable to the sponsor.7
Similarly, a cross-sectional study of randomised trials
found those authored by principal investigators with
ties to pharmaceutical companies were more likely than
other trials to report favourable results.8 Such evidence
has provoked debate about the optimum constitution of
guideline groups, with calls for chairs and a majority of
writers to be free of financial ties,9 10 as well as recommen-
dations for exclusion of any conflicted writer.2
In Australia, the publicly funded National Health
and Medical Research Council (NHMRC) is currently
engaged in improving standards for guideline develop-
ment, including in relation to transparency and manage-
ment of conflicts of interest. An internal analysis of 9 years
of Australian guidelines made available via the NHMRC
guideline portal, 2005–2013, found only 12% of guide-
lines published declarations of the conflicts of interest
of guideline writers.11 As part of work to improve stan-
dards of guidelines which can have direct impacts on how
clinicians deliver care to their patients, the NHMRC is
developing new ‘guidelines for guidelines’, and a draft
released for public comment in 2017 included the recom-
mendation: “Organisations planning guidelines should
aim to appoint a guideline development group whose
members have no financial or other links with relevant
industry groups”.12 In order to inform ongoing efforts to
improve guideline quality in Australia and internation-
ally, our objective was to investigate the extent of undis-
closed financial ties to industry, for a broad cross-section
of guideline writers from different categories of guide-
line developer, sampled from a comprehensive national
guideline database, across a wide spectrum of diseases.
METHODS
We conducted a cross-sectional study of a stratified
random sample of Australian clinical practice guidelines
and followed the STROBE checklist for reporting obser-
vational studies (see online supplementary file 1).13
Sampling guidelines
We identified a stratified random sample of clinical
practice guidelines from within the NHMRC guidelines
database, across nine government-designated health
priority areas (https:// nhmrc. gov. au/ about- us/ publi-
cations/ nhmrc- corporate- plan- 2017- 2018) plus kidney/
urogenital, published in the years 2012–2014. The
NHMRC database comprised guidelines made available
on the publicly accessible NHMRC guidelines portal,
which aimed to include all Australian guidelines,
defined broadly as published articles making clinical
recommendations. While the NHMRC portal at that
time included all Australian guidelines, it also provided
users of the portal with information on quality indica-
tors for these guidelines, such as whether the guideline
was based on a systematic review of evidence, whether
the authors provided conflict of interest disclosures
and whether or not the guideline had been approved
by NHMRC. From 2015, the NHMRC portal restricted
the inclusion of guidelines to only include guidelines
which met certain quality standards, so to achieve a
representative sample from the comprehensive collec-
tion of widely used Australian guidelines, we analysed
guidelines available on the portal in the 3 years leading
up to the change.
In 2017, NHMRC staff (HJ) identified all guidelines
in the database, published in the years 2012–2014, and
used previous coding by NHMRC to exclude articles
not relevant to the 10 health areas of interest, those
not considered guidelines, including those coded as
Evidence Reviews, Posters/Flowcharts, Standards and
Summary guidelines. Following the initial screen, each
guideline was randomly ordered using Microsoft Excel
within each of the 10 health areas. Two authors (LB,
RM) then assessed each guideline in the order they had
been ranked, against explicit inclusion criteria, and iden-
tified guideline writers to be included in the analysis.
Guidelines were included if they were associated with a
professional organisation or entity and made mention
of medicines in recommendations. They were excluded
if they were a journal article unconnected from an
external organisation, or if no author names or full text
was available. Guideline writers listed in the guideline
were included for analysis if they were explicitly engaged
in developing, preparing or writing the guideline, and
excluded if they were external consultants, members
of oversight committees or staff from a drug company,
NHMRC or administrative staff. Any discrepancies were
resolved by discussion.
The primary unit of analysis was the guideline writer.
Based on assumptions that 10% of guideline writers
might have an undisclosed relevant financial tie, and that
guidelines would have 4–20 writers each, we estimated a
need for a minimum sample of 12 guidelines—aiming for
approximately 140 writers—to produce a CI of a width
of 10% around our estimate of the proportion of writers
with undisclosed ties. In addition, to obtain as broad a
cross-section as possible, we aimed to analyse up to four
guidelines per health priority/disease area, depending
on guideline availability.
on 6 February 2019 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2018-025864 on 5 February 2019. Downloaded from
3
MoynihanR, etal. BMJ Open 2019;9:e025864. doi:10.1136/bmjopen-2018-025864
Open access
Guideline and author information
One investigator (either AL or RM) extracted all rele-
vant information from each included guideline into
the REDCap electronic data capture tools hosted at
the University of Sydney.14 The extracted information
included the names of all included writers, classified in
one of three ways: disclosure of ties; disclosure of no ties;
no disclosure present. Disclosures were those included in
the guideline document or associated publicly available
documents. Information on whether the guideline had
a statement on conflicts of interest, and the developer/s
and funder/s was also extracted.
Identication of potentially relevant undisclosed nancial ties
For any guideline writer with no declaration present, or
who declared no conflicts of interests, one investigator
(AL or RM) conducted a search of the writer’s publica-
tions in the 5 years before the year of guideline publica-
tion. The period of 5 years was chosen for the following
reasons: many guidelines are estimated to be at least
2 years in development before the year of publication;
disclosures are directly relevant at the start of the process
of guideline development; WHO guidance suggests a
period of 4 years prior to publication is relevant when
disclosing financial ties15; many disclosure policies have
a recall period of 3 to 5 years.16 Publications were also
searched in the 3 years following guideline publication,
as some organisations, including the Institute of Medi-
cine, recommend guideline writers be free of conflicts for
periods of time after guideline publication.17
The Scopus database was used to search for publications
of guideline writers using their names and affiliations.
Full texts were obtained. Searches were conducted from
the earliest date and as per Forsyth et al18 were stopped
once a potentially relevant financial tie was identified. A
potentially relevant tie was defined as a financial tie to
a pharmaceutical company actively marketing or in late
stages of bringing a medicine to market in the therapeutic
area relevant to the guideline, at the time of the guideline
publication, determined through searches of company
websites and relevant product information material. Cate-
gorisation of ties was developed based on criteria set by
the International Committee of Medical Journal Editors,
ICMJE, and based on adaptations of ICMJE criteria
used in a previous study,18 including grants (funding
for research study), personal fees (consulting, advisory,
speakers, honoraria, travel), patents/copyrights/royal-
ties and miscellaneous. Once a potentially relevant tie was
identified by one author (AL or RM), a second author
(RM or LB) double checked the full text of the disclosure
and verified the tie as a potentially relevant tie, and any
discrepancies were resolved by discussion. Searches were
conducted between August and December 2017.
Outcome measures and statistical analysis
The primary outcome measures were specified as the
proportion of guideline writers with potentially rele-
vant undisclosed ties, and the proportion of guidelines
in the sample which included at least one writer with an
undisclosed tie. Secondary outcome measures were the
proportion of writers with disclosed ties, the proportion
of guidelines which have any statement about conflicts
of interest, and the proportion of guidelines developed
and funded by governments (state, federal or territories).
We report data proportions using descriptive statistics
and including 95% CIs. We examined the association
between having statements and the proportion of poten-
tially relevant undisclosed ties of writers, and the associa-
tion between a guideline being developed and funded by
government/s and the proportion of potentially relevant
undisclosed ties of writers. Potential associations were
tested using the χ2 test. CIs were not adjusted for clus-
tering of writers within multiple guidelines or for clus-
tering of guidelines within disease area.
Ethics
As all publications analysed for this study were on the
public record, the chair of Bond University’s Human
Research Ethics committee asserted that the study did not
require ethics review if no individuals were identified or
described.
Patient and public involvement
No patients or members of the public were involved in
this study.
RESULTS
Characteristics of guidelines
There was a total of 347 guidelines in the NHMRC data-
base, published 2012–2014 (figure 1). The initial screen
excluded 11 items not considered guidelines, coded by
NHMRC as Evidence Reviews, Posters/Flowcharts, Stan-
dards and Summary guidelines, 62 because they did not
contain names of those who had developed the guideline
and 129 published outside the 10 health areas in this study.
The remaining 145 guidelines were assigned a random
number to establish a random order for assessment of
the guidelines within each of the 10 health areas. We
continued to assess guidelines within each area in random
order until we had included four for each health area or
had completed assessing all the available guidelines in a
given health area. In total, LB and RM assessed 82 guide-
lines. Forty-nine of those guidelines were excluded after
assessment because they were a publication only with no
affiliation to any external organisation (n=22), had no
recommendations about medications (n=25), or the full
text or author list of the guideline was not publicly avail-
able (n=2). Sixty-three were not assessed.
We included 33 guidelines in our final sample: arthritis/
musculoskeletal (n=3); asthma (n=4); cancer (n=4);
cardiovascular (n=4); diabetes (n=4); injury (n=4); mental
health (n=4); neurological (n=1); obesity (n=1); kidney/
urogenital (n=4) (online supplementary file 2). The 33
guidelines involved a total of 402 guideline writers, with
on 6 February 2019 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2018-025864 on 5 February 2019. Downloaded from
4MoynihanR, etal. BMJ Open 2019;9:e025864. doi:10.1136/bmjopen-2018-025864
Open access
individual guidelines having between 2 and 35 writers
included for analysis.
Prevalence of undisclosed ties
Among all 402 guideline writers, 58 disclosed ties (14%;
95% CI 11% to 18%) (table 1). Among the 402 writers,
344 had no disclosed ties (86%; 95% CI 82% to 89%),
including 228 writers where no disclosures appeared
and 116 writers with statements that they had no ties. Of
the 344 writers with no disclosed ties, 83 had at least one
potentially relevant undisclosed tie (24%; 95% CI 20%
to 29%), discovered in the published literature in the
same year as the guideline was published or the previous
5 years. Of those undisclosed ties, the first category of
tie listed in the relevant disclosure was pharmaceutical
company grant (64%) or personal fees (36%). If the time
frame was extended to 3 years after the guideline, the
proportion of potentially relevant undisclosed ties rose
from 24% to 28% (95% CI 23% to 33%).
Of 33 guidelines, 23 included at least one writer with
a potentially relevant undisclosed tie (70%; 95% CI 51%
to 84%) (figure 2). Of those 23 guidelines, 14 guidelines
had 20% or more writers who disclosed no ties, but had
potentially relevant undisclosed ties. Figure 2 also reveals
the proportion of undisclosed ties of guideline writers
who disclosed no ties, per guideline, grouped by disease
category.
Guideline characteristics and undisclosed ties
Guidelines which included any statement about conflicts
of interest were not significantly different from those
without statements: 59 of 223 writers (27%) had poten-
tially relevant undisclosed ties, compared with 24 of
121 writers (20%) (risk ratio 1.33; 95% CI 0.88 to 2.03;
p=0.170) (table 2). Guidelines both developed and
funded by governments, as opposed to non-government
groups (including professional bodies, foundations or
pharmaceutical companies), were significantly less likely
to have authors with potentially relevant undisclosed ties:
8 of 99 writers (8%) compared with 75 of 245 writers
(31%) (risk ratio 0.26; 95% CI 0.13 to 0.53; p<0.001).
Figure 1 Flowchart for sample.NHMRC,National Health and Medical Research Council.
on 6 February 2019 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2018-025864 on 5 February 2019. Downloaded from
5
MoynihanR, etal. BMJ Open 2019;9:e025864. doi:10.1136/bmjopen-2018-025864
Open access
DISCUSSION
In this broad cross-sectional sample of Australian clin-
ical practice guidelines, 14% of guideline writers had
published disclosures of conflicts of interest. Among
those who either had no disclosures or disclosed they
had no conflicts, 24%—almost one in four—had at
least one potentially relevant undisclosed financial
tie to a pharmaceutical company active in the thera-
peutic area. More than two-thirds, or 70%, of the 33
guidelines in this sample had at least one writer with
an undisclosed tie. Undisclosed financial ties of guide-
line writers appeared to be more common in some
therapeutic areas such as diabetes and cardiovascular
disease, compared with other areas such as injury and
mental health. Guideline writers working on guidelines
developed and funded by government were much less
likely to have undisclosed financial ties: 8% compared
with 31%.
Table 1 Characteristics of guideline writers from a stratied random sample of guidelines, 2012–2014 (n=33)
Therapeutic
area
Clinical practice
guideline (ID
number)
Total number of
writers
Number with
disclosed ties
Number with no
disclosed ties
COI statement
available
Developed
and funded by
government
Arthritis 1 15 0 15 Yes No
2 26 2 24 Yes No
3 6 0 6 No Yes
Asthma 4 14 0 14 No Yes
5 7 0 7 No No
6 6 0 6 No No
7 6 4 2 Yes No
Cancer 8 27 4 23 Yes No
9 6 1 5 Yes No
10 14 0 14 Yes Yes
11 31 0 31 No Yes
Cardiovascular 12 11 4 7 Yes No
13 4 0 4 No No
14 8 1 7 Yes No
15 34 0 34 Yes No
Diabetes 16 4 0 4 No No
17 14 0 14 No No
18 5 5 0 Yes No
19 13 0 13 Yes No
Injury 20 18 0 18 No Yes
21 2 0 2 No Yes
22 35 4 31 Yes No
23 9 0 9 Yes Yes
Kidney 24 7 1 6 Yes No
25 9 2 7 Yes No
26 6 2 4 Yes No
27 13 0 13 No No
Mental health 28 10 10 0 Ye s Ye s
29 11 11 0 Ye s Ye s
30 9 0 9 Yes No
31 8 0 8 Yes No
Neurological 32 2 0 2 No No
Obesity 33 12 7 5 Ye s Ye s
Total 402 58 344
COI, conict of interest.
on 6 February 2019 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2018-025864 on 5 February 2019. Downloaded from
6MoynihanR, etal. BMJ Open 2019;9:e025864. doi:10.1136/bmjopen-2018-025864
Open access
There are important limitations to this study. First, the
results likely underestimate the frequency of undisclosed
ties for several reasons: there is a general under-reporting
of ties published in medical journals as many important
transfers of benefits to professionals, such as hospitality
or industry-subsidised education, are not routinely
disclosed; Australia did not at the time have a database
with information on company payments to individuals;
and we did not search for any potentially relevant undis-
closed ties of writers who made disclosures of ties in the
guideline, whether those ties were to pharmaceutical
companies or other groups. Second, our results may tend
to a small degree to overestimate the frequency of undis-
closed ties, through what some may see as a broad defi-
nition of potential relevance; for example, categorising
a co-investigator of a study funded by a pharmaceutical
company active in the therapeutic area as a potentially
relevant tie. Third, the sample of guidelines, while broad
and accessible, comes from 2012 to 2014—the most
recent years available for this sample from a comprehen-
sive collection—admitting the possibility of change since
that time. And fourth, we looked only at financial ties, not
other non-financial conflicts of interest. The strengths
of the study lie in it being the largest to date in terms
of guideline writers and undisclosed ties to industry, as
well as covering a broad cross-section of disease catego-
ries and guideline developers—both government and
non-government—with previous smaller studies limited
to specific therapeutic areas,4 5 or guidelines produced
only by specialty societies.6
Neuman and colleagues investigated the prevalence of
conflicts of interest among panels producing 14 North
American guidelines for high cholesterol and diabetes.4
They reported that among writers who formally declared
no conflicts, 11% had one or more. Looking at a small
sample of 49 writers of head and neck surgery guide-
lines, Horn and colleagues found 6% had discrepancies
between guideline disclosures and information available
in the Open Payments transparency database.5 Analysing
Danish specialty society guidelines, and cross-checking
disclosures against a public register of disclosures, Bind-
sley and colleagues estimated 52% of 254 guideline writers
had not disclosed ties.6 A possible explanation of why our
estimate of 24% sits within these finding is that the North
American studies used narrower timeframes to search for
undisclosed ties, while the Danish study defined a conflict
of interest as any affiliation with any drug company.
As others have stated, guideline writer ties to compa-
nies with interest in the guideline’s outcome raise crit-
ical questions about potential bias in processes that may
have great impacts on the use of healthcare interven-
tions,4 12 disease definitions19 and patient care. Findings
of potentially relevant undisclosed ties compound the
problem further and raise the spectre of hidden bias,
increasing the wariness of guideline users. Contemporary
community standards now demand total transparency,
and our findings of undisclosed ties add weight to calls
for reforms like the Sunshine Act and Open Payments
system in the USA,20 ‘publicly accessible registries of
researcher conflicts of interest’,21 and more immediately,
Figure 2 Proportion of Australian clinical practice guideline writers with undisclosed ties, 2012–2014.
Table 2 Proportion of guidelines writers with undisclosed nancial ties by guideline type
Yes No Risk ratio (95% CI) Pvalue
COI statement in
guideline
59/223 (26.5%) 24/121 (19.8%) 1.33 (0.88 to 2.03) 0.170
Developed, funded by
government/s
8/99 (8.1%) 75/245 (30.6%) 0.26 (0.13 to 0.53) <0.001
Pvalue refers to χ2 test.
COI, conict of interest.
on 6 February 2019 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2018-025864 on 5 February 2019. Downloaded from
7
MoynihanR, etal. BMJ Open 2019;9:e025864. doi:10.1136/bmjopen-2018-025864
Open access
enforcement of current disclosure policies to minimise
undisclosed ties. In line with repeated recommendations
for greater independence between health professionals
and industry,1 2 12 our incidental finding that almost one
in five of these guidelines had less than 10% of writers
with any ties to industry shows it is possible to assemble
guideline panels almost entirely free of financial conflicts
of interest.
The related reform processes of enhanced transparency
and greater independence underway in many nations
creates clear opportunities for research comparing the
quality of guidelines developed by writers with and without
links to industry, a research question beyond the scope of
this study, and where there are currently limited data.22
Similarly, there is a need for more research investigating
the impacts of links between industry and the professional
organisations which auspice guideline development, with
one recent study suggesting such ties are ‘common and
infrequently disclosed’.23 Given their potential influence
over human health, and health system sustainability, such
vital research on the independence and trustworthiness
of guidelines will be greatly enhanced by complete trans-
parency around the financial conflicts of interest of those
developing them.
Acknowledgements We would like to thank Edward Luca, who helped develop the
search for guideline writer publications.
Contributors RM, AL, HJ, GD, SG and LB conceived and designed the study. RM
and LB supervised the study. RM, AL, EB and LB analysed the data. RM, AL, HJ, GD,
SG, EB and LB interpreted the data. RM wrote the rst draft of the manuscript, and
RM, AL, HJ, GD, SG, EB and LB were involved in revisions of the manuscript. RM and
LB are guarantors. All authors contributed to the planning, conduct and reporting of
this study. All authors had full access to all data and can take responsibility for the
integrity of the data analysis.
Funding RM is supported by a research fellowship funded by NHMRC,
GNT1124207. EB is supported by grants from NHMRC to the Centre for Research in
Evidence-Based Practice, Bond University.
Competing interests HJ was an employee of NHMRC. SG and GD are employees
of NHMRC. LB is an employee of The University of Sydney and had no funding
specically for this work.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement We will share data where possible, within connes of
guidance from Bond University Ethics Committee that the paper does not identify or
describe any individuals.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the use
is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.
REFERENCES
1. Lo B, Field MJ. Conict of interest in medical research, education,
and practice. Editors: Institute of Medicine (US) Committee on
conict of interest in medical research, education, and practice.
Washington (DC): National Academies Press (US), 2009.
2. Institute of Medicine. Clinical Practice Guidelines We Can Trust,
Report Brief. Washington, DC: The National Academies Press, 2011.
3. Norris SL, Holmer HK, Ogden LA, et al. Conict of interest in clinical
practice guideline development: a systematic review. PLoS One
2011;6:e25153.
4. Neuman J, Korenstein D, Ross JS, et al. Prevalence of nancial
conicts of interest among panel members producing clinical
practice guidelines in Canada and United States: cross sectional
study. BMJ 2011;343:d5621.
5. Horn J, Checketts JX, Jawhar O, et al. Evaluation of industry
relationships among authors of otolaryngology clinical practice
guidelines. JAMA Otolaryngol Head Neck Surg 2018;144:194.
6. Bindslev JB, Schroll J, Gøtzsche PC, et al. Underreporting of
conicts of interest in clinical practice guidelines: cross sectional
study. BMC Med Ethics 2013;14:19.
7. Lundh A, Lexchin J, Mintzes B, et al. Industry sponsorship and
research outcome cochrane database of systematic reviews. First
published 16 February 2017.
8. Ahn R, Woodbridge A, Abraham A, et al. Financial ties of principal
investigators and randomized controlled trial outcomes: cross
sectional study. BMJ 2017;356:i6770.
9. Guyatt G, Akl EA, Hirsh J, et al. The vexing problem of guidelines
and conict of interest: a potential solution. Ann Intern Med
2010;152:738–41.
10. Handbook for Guideline Development. WHO 2nd ed. Geneva, 2014.
11. National Health and Medical Research Council. Annual Report on
Australian Clinical Practice Guidelines. Canberra: National Health and
Medical Research Council, 2014.
12. National Health and Medical Research Council. Identifying and
managing conicts of interest. NHMRC Public Consultation Version
2017 https:// consultations. nhmrc. gov. au/ les/ consultations/ drafts/
iden tify inga ndma nagi ngco ni ctso nt erest. pdf (accessed 12 Apr
2018).
13. STROBE Statement—Checklist of items that should be included in
reports of cross-sectional studies. https://www. strobe- statement. org/
leadmin/ Strobe/ uploads/ checklists/ STROBE_ checklist_ v4_ cross-
sectional. pdf (accessed 12 Apr 2018).
14. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture
(REDCap)-a metadata-driven methodology and workow process for
providing translational research informatics support. J Biomed Inform
2009;42:377–81.
15. World Health Organization. WHO Conict of Interest Guidelines:
declaration of interests for WHO experts, 2010. http:// keionline. org/
node/ 1062. (accessed 12 Apr 2018).
16. Boyd EA, Bero LA. Improving the use of research evidence in
guideline development: 4. Managing conicts of interests. Health Res
Policy Syst 2006;4:16.
17. Institute of Medicine, Board on Health Care Services. Committee on
Standards for Developing Trustworthy Clinical Practice Guidelines.
Clinical Practice Guidelines we can trust. Washington, DC: National
Academies Press, 2011.
18. Forsyth SR, Odierna DH, Krauth D, et al. Conicts of interest and
critiques of the use of systematic reviews in policymaking: an
analysis of opinion articles. Syst Rev 2014;3:122.
19. Moynihan RN, Cooke GP, Doust JA, et al. Expanding disease
denitions in guidelines and expert panel ties to industry: a cross-
sectional study of common conditions in the United States. PLoS
Med 2013;10:e1001500.
20. Centres for Medicare & Medicaid Services, Open Payments
database. https://www. cms. gov/ openpayments/ (accessed 12 Apr
2018).
21. Dunn AG, Coiera E, Mandl KD, et al. Conict of interest disclosure in
biomedical research: a review of current practices, biases, and the
role of public registries in improving transparency. Res Integr Peer
Rev 2019;1:1. Epub 2016 May 3.
22. Cosgrove L, Bursztajn HJ, Erlich DR, et al. Conicts of interest and
the quality of recommendations in clinical guidelines. J Eval Clin
Pract 2013;19:674–81.
23. Campsall P, Colizza K, Straus S, et al. Financial relationships
between organizations that produce clinical practice guidelines
and the biomedical industry: a cross-sectional study. PLoS Med
2016;13:e1002029.
on 6 February 2019 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2018-025864 on 5 February 2019. Downloaded from
... Regarding this period, we collected payment data from 2016 to 2018 because most Japanese professional medical associations ask for COI declarations three years before the publication of a guideline. Additionally, we collected data two years after a guideline publication because some organizations, including the Institute of Medicine, recommend that guideline developers remain free of conflicts for this time period after the guideline is published [19]. ...
... A total of 18 authors (78.3%) in Japan and 12 authors (48.0%) in the USA had undisclosed financial COIs worth $474,663 and $218,501, respectively. In the 2012-2014 Australian CPGs, 24% of CPG developers had at least one potentially relevant undisclosed COI [19]. Of these undisclosed relationships, the first category of relationship listed in the relevant disclosure was pharmaceutical company grants (64%) or personal fees (36%). ...
Article
Full-text available
Accurate disclosure of financial conflicts of interest (COI) among clinical practice guideline (CPG) developers is critical to ensure the quality of CPGs. However, there is limited evidence on the impact of underreporting COIs on the quality of CPGs. This study aimed to examine the proportion of underreported COI disclosure in the development of Japanese CPGs and to estimate the association between underreported COI and CPG quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II. Twenty-three Japanese CPGs published in 2019 and their 1114 developers were included in the study. The results shows that underreporting of COIs occurred in 52% of the included CPGs and 8% of all CPG developers. Underreporting COI disclosure was negatively associated with low-quality CPG (Odds ratio [OR], 0.57; 95% confidence interval [CI]: 0.11, 3.04). On the other hand, CPGs with more than 13% of CPG developers with underreporting COI disclosure who have voting right on recommendation decision were positively associated with low quality (OR,1.78; 95% CI: 0.25, 12.45). For individual CPG developers with voting rights for recommendation decisions, the presence of a COI was positively associated with low quality (OR, 1.11; 95% CI: 0.71, 1.75). This study demonstrates that the involvement and underreporting of COIs did not seriously distort the CPG development process. However, the COI-related factors of CPG developers with voting rights for recommendation decisions may be associated with low CPG quality.
... However, the credibility of these guidelines is often at risk due to potential conflicts of interest (COIs) among CPG developers. Over recent years, there has been a growing focus on the financial relationships between CPG developers and the healthcare industry, both within Japan and globally [3][4][5][6][7][8][9]. While not all financial interactions could lead to problematic relationships and harmful influence on patients, some can introduce bias into CPG recommendations, potentially endangering patient-centered care [2,10,11]. ...
Article
Full-text available
Background Financial relationships between clinical guideline authors and pharmaceutical companies introduce conflicts of interest (COI), potentially biasing guideline recommendations. Thus, proper management of COI is paramount for clinical guideline authors. Nevertheless, little is known about COI among neurology clinical guideline authors. This study aimed to evaluate the financial relationships between pharmaceutical companies and authors of Clinical Practice Guideline for Headache Disorders (CPGHD) in Japan. Methods This is a retrospective analysis of 2016–2020 personal payments data disclosed by all pharmaceutical companies affiliated with the Japan Pharmaceutical Manufacturers Association. We examined amounts and fraction of personal payments to all 57 CPGHD authors and all neurologists board-certified by the Japanese Society of Neurology. Payment data was descriptively analyzed at individual author level. Results Among 57 CPGHD authors, 56 (98.3%) received personal payments totaling 2.7millionfrompharmaceuticalcompaniesbetween2016and2020.Medianfiveyearpaymentswere2.7 million from pharmaceutical companies between 2016 and 2020. Median five-year payments were 89,955 for CPGHD authors, while $521 for board-certified neurologists. The CPGHD chairperson and vice chairperson received substantial payments during the guideline development period. Nevertheless, because of less rigorous and transparent COI policy compared to international standard policies, only 10 authors disclosed their financial relationships with the pharmaceutical companies in the guideline. Conclusions More than 98% of CPGHD authors received much higher personal payments from pharmaceutical companies than those to board-certified neurologists during the guideline development period in Japan.
... Over the past decade, accumulating evidence has shown prevalent financial relationships between CPG authors and the healthcare industry. [3][4][5][6][7][8][9] While not all financial interactions necessarily lead to problematic relationships or harmful influences on patients and physicians' clinical practice, some can introduce bias into CPG recommendations, potentially compromising patient-centered care. 2,10,11 A recent systematic review indicated that CPGs and advisory committee reports with COIs were more likely to make favorable recommendations for pharmaceutical companies. ...
... Clinical practice guidelines are increasingly used by physicians to guide treatment decisions, and the pharmaceutical industry focuses on influencing the authors of these guidelines. Almost one in four guideline writers with no disclosed ties may have potentially relevant undisclosed ties to pharmaceutical companies [2]. Doctors are in a fiduciary relationship with patients and expected to act in their best interests. ...
... Medication requests for hemato/oncological indications were excluded (60% of total requests), as serial published government yearly reports have shown that over 50% of annual supplements to the NDF budget are regularly preallocated for hemato/oncology drugs. This is probably due to strong public advocacy demands, likely driven by pharmaceutical industry advertising and possible influence on expert opinion leaders, who participate ex-officio in national policy making, as shown in other countries [17][18][19][20]. For each submitted request, data were collected on patient demographics (gender, age), submitting physician (GP vs. specialist), and components of the decision process itself, recorded and dichotomously categorized as follows: ...
Article
Full-text available
Background In Israel, coverage of health needs is delivered by four health maintenance organizations (HMOs), which are budgeted by the government according to the recommendations of the National Drug Formulary (NDF) Committee. For medications not listed in the NDF, individuals may request to cover the costs by the HMO Exemptions Committee (DEC). The objectives of the current study, a first of its kind, are to document the DEC decision process, to identify its components and to determine the decisions’ clinical outcome. Methods This retrospective cohort study included all members (≥ age 18) of the Maccabi Healthcare Service (MHS) who submitted a request to the DEC between June 2017 and December 2018. Collected data include patient demographics, clinical information and components of the decision process. Decision success (i.e., clinical outcome correlated with DEC decision) was determined by clinical outcome over at least one-year follow-up. Results A total of 335 requests were included. Strong evidence and rare disease were positively associated with approvals, while the availability of alternative treatments and costs were negatively associated. The majority of decisions (75%) met predicted clinical outcomes. Only estimated costs were found to be associated with decision success. Conclusions Factors that reduce the potential costs of a requested drug are significantly associated with higher odds for drug approval, but only when the evidence supports potential benefit.
... 1,2 However, compiling evidence suggests that the financial conflicts of interest (COIs) between drug companies and the CPG authors potentially compromise the credibility of the guidelines. [3][4][5][6][7][8][9][10][11][12][13] These concerns jeopardise the trust in drug companies and draw attention. 1,2,5,[14][15][16][17][18] Given the profound impact of CPGs on patients, clinicians and various stakeholders, and their perception as guiding principles for physicians, 19 rigorous COI management strategies, encompassing minimisation of COIs among authors and guideline-producing societies, full disclosure of financial COIs and the appointment of COI-free CPG chairs, are indispensable. ...
Article
Full-text available
Background The creation of breast cancer practice guidelines requires proper management of financial relationships with drug companies, as they can introduce conflicts of interest (COIs) among guideline authors. However, little is known about the specific landscape and fraction of financial interactions between the authors of the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, edition 2022 (JBCS2022) and drug companies. Methods Using payment data publicly disclosed by major drug companies in Japan, this study analysed the personal payments made to the authors of JBCS2022 between 2016 and 2020. We performed descriptive analyses on the payment data. Results Of the 149 JBCS2022 authors, 115 (77.2%) received at least one personal payment totaling 3828455fromdrugcompaniesbetween2016and2020.Theaverageandmedianpaymentamountsperauthorwere3 828 455 from drug companies between 2016 and 2020. The average and median payment amounts per author were 25 772 (standard deviation: 58197)and58 197) and 2761 (interquartile range: 322322‒15 828), respectively. The total annual payments per JBCS2022 authors between 2016 and 2019 increased from 588054in2016to588 054 in 2016 to 967 802 in 2019. The JBCS2022 chairperson and vice‐chairperson received 246936(fourthhighest)and246 936 (fourth highest) and 216 744 (fifth highest) over the 5 years. More than 60% of personal payments to the JBCS2022 authors were not declared by the authors as they were below the declaration threshold set by the Japanese Breast Cancer Society. However, nine authors undeclared personal payments summing $594 615 even though these payments were higher than the thresholds. Conclusion This study demonstrated that the majority of the breast cancer guideline authors received personal payments from drug companies in Japan. Furthermore, the majority of payments were not declared because of the less transparent COI policy.
... Over the past decade, accumulating evidence has shown prevalent financial relationships between CPG authors and the healthcare industry. [3][4][5][6][7][8][9] While not all financial interactions necessarily lead to problematic relationships or harmful influences on patients and physicians' clinical practice, some can introduce bias into CPG recommendations, potentially compromising patient-centered care. 2,10,11 A recent systematic review indicated that CPGs and advisory committee reports with COIs were more likely to make favorable recommendations for pharmaceutical companies. ...
... Consequently, many academic journals, professional medical societies, and governmental bodies mandate the disclosure of industry-sponsored research participation and funding. Despite these regulations, disclosures are sometimes incomplete or inaccurately reported [39][40][41][42]. At a minimum, all physicians, including PHOs, should maintain transparency regarding their financial relationships with the healthcare industry, especially when involved in industry-sponsored research. ...
Article
Financial interactions between healthcare industry and pediatric hematologist/oncologists (PHOs) could be conflicts of interest. Nevertheless, little is known about financial relationships between healthcare industry and PHOs. This cross-sectional analysis of the Open Payments Database examined general and research payments to PHOs from healthcare industry in the United States between 2013 and 2021. Payments to the PHOs were analyzed descriptively. Trends in payments were assessed using generalized estimating equation models. Of 2784 PHOs, 2142 (76.9%) PHOs received payments totaling 187.3millionfromthehealthcareindustrybetween2013and2021.Approximately,187.3 million from the healthcare industry between 2013 and 2021. Approximately, 46.3 million (24.8%) were general payments and $137.7 million (73.5%) were funding for research where PHOs served as principal investigators (associated research funding). Both general payments and associated research funding considerably increased between 2014 and 2019. The number of PHOs receiving general payments and associated research funding annually increased by 2.2% (95% CI: 1.2-3.3%, p < .001) and 5.0% (95% CI: 3.3-6.8%, p < .001) between 2014 and 2019, respectively.
... 30 However, it has been shown that many guideline authors have potentially relevant undisclosed COI and COI management is often inadequate. 30,34,35 It is not yet known, to what extent policies and standards for management and disclosure of COI have been adopted for the development of guidelines on ECAP and whether this point is also acknowledged in FBDGs. [35][36][37] It is also not clear, whether COI in guideline development are associated with the content of the recommendations and with the prevalence of intervention-and industry-friendly recommendations. ...
Article
Full-text available
Background With the rising prevalence of allergic diseases in children, prevention of childhood allergies becomes an important public health issue. Recently, a paradigm shift is taking place in the approach to preventing allergies, and clinical practice guidelines (CPG) and food-based dietary guidelines (FBDG) play an important role in providing practitioners with the latest evidence and reliable guidance. However, concern about the methodological quality of the development of FBDGs and CPGs, including limitations in the systematic reviews, lack of transparency and unmanaged conflicts of interest (COI), reduce the trust in these guidelines. Methods We aim to synthesize the available guidance on early childhood allergy prevention (ECAP) through a systematic search for national and international CPGs and FBDGs concerning ECAP and child nutrition (CN) and to assess the quality of the guidelines and management of COI. Additionally, we will analyse the content and the evidence base of the recommendation statements. We aim to quantify the COI in guideline panellists and explore possible associations between COI and recommendations. Through a social network analysis, we expect to elucidate ties between panellists, researchers, institutions, industry and other sponsors. Guidelines are an important tool to inform healthcare practitioners with the newest evidence, but quality and reliability have to be high. This study will help identify potential for further improvement in the development of guidelines and the management of COI. If the social network analysis proves feasible and reveals more information on COI in comparison to disclosed COI from the previous analyses, the methodology can be developed further to identify undisclosed COIs in panelists. Ethics and dissemination This research does not require ethical approval because no human subjects are involved. Results will be published in international peer-reviewed open access journals and via presentations at scientific conferences.
Article
Full-text available
Purpose Clinical research is widely sponsored by drug and device companies. We investigated whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. This review is an update of a previous Cochrane review. Methods In this update we searched MEDLINE and Embase (2010 to February 2015), Cochrane Methodology Register (2015, Issue 2) and Web of Science (June 2015). We included empirical studies that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. Two assessors included papers, extracted data and assessed risk of bias. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether conclusions agreed with results. Results We included 27 additional papers in this update (review now includes 75 papers). Industry sponsored studies more often had favorable efficacy results, RR: 1.27 (95% CI 1.17–1.37), no difference in harms results RR: 1.37 (95% CI 0.64–2.93) and more often favorable conclusions RR: 1.34 (95% CI 1.19–1.51) compared with non-industry sponsored studies. Nineteen papers reported on sponsorship and efficacy effect size, but could not be pooled due to differences in reporting of data and heterogeneity of results. Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.25 (95% CI 1.05–1.50), compared with non-industry sponsored studies. Conclusions Drug and device studies sponsored by manufacturing companies have more favorable efficacy results and conclusions than studies sponsored by other sources.
Article
Full-text available
Objective To examine the association between the presence of individual principal investigators’ financial ties to the manufacturer of the study drug and the trial’s outcomes after accounting for source of research funding. Design Cross sectional study of randomized controlled trials (RCTs). Setting Studies published in “core clinical” journals, as identified by Medline, between 1 January 2013 and 31 December 2013. Participants Random sample of RCTs focused on drug efficacy. Main outcome measure Association between financial ties of principal investigators and study outcome. Results A total of 190 papers describing 195 studies met inclusion criteria. Financial ties between principal investigators and the pharmaceutical industry were present in 132 (67.7%) studies. Of 397 principal investigators, 231 (58%) had financial ties and 166 (42%) did not. Of all principal investigators, 156 (39%) reported advisor/consultancy payments, 81 (20%) reported speakers’ fees, 81 (20%) reported unspecified financial ties, 52 (13%) reported honorariums, 52 (13%) reported employee relationships, 52 (13%) reported travel fees, 41 (10%) reported stock ownership, and 20 (5%) reported having a patent related to the study drug. The prevalence of financial ties of principal investigators was 76% (103/136) among positive studies and 49% (29/59) among negative studies. In unadjusted analyses, the presence of a financial tie was associated with a positive study outcome (odds ratio 3.23, 95% confidence interval 1.7 to 6.1). In the primary multivariate analysis, a financial tie was significantly associated with positive RCT outcome after adjustment for the study funding source (odds ratio 3.57 (1.7 to 7.7). The secondary analysis controlled for additional RCT characteristics such as study phase, sample size, country of first authors, specialty, trial registration, study design, type of analysis, comparator, and outcome measure. These characteristics did not appreciably affect the relation between financial ties and study outcomes (odds ratio 3.37, 1.4 to 7.9). Conclusions Financial ties of principal investigators were independently associated with positive clinical trial results. These findings may be suggestive of bias in the evidence base.
Article
Full-text available
Background: Financial relationships between organizations that produce clinical practice guidelines and biomedical companies are vulnerable to conflicts of interest. We sought to determine whether organizations that produce clinical practice guidelines have financial relationships with biomedical companies and whether there are associations between organizations' conflict of interest policies and recommendations and disclosures provided in guidelines. Methods and findings: We conducted a cross-sectional survey and review of websites of 95 national/international medical organizations that produced 290 clinical practice guidelines published on the National Guideline Clearinghouse website from January 1 to December 31, 2012. Survey responses were available for 68% (65/95) of organizations (167/290 guidelines, 58%), and websites were reviewed for 100% (95/95) of organizations (290/290 guidelines, 100%). In all, 63% (60/95) of organizations producing clinical practice guidelines reported receiving funds from a biomedical company; 80% (76/95) of organizations reported having a policy for managing conflicts of interest. Disclosure statements (disclosing presence or absence of financial relationships with biomedical companies) were available in 65% (188/290) of clinical practice guidelines for direct funding sources to produce the guideline, 51% (147/290) for financial relationships of the guideline committee members, and 1% (4/290) for financial relationships of the organizations producing the guidelines. Among all guidelines, 6% (18/290) disclosed direct funding by biomedical companies, 40% (117/290) disclosed financial relationships between committee members and biomedical companies (38% of guideline committee members, 773/2,043), and 1% (4/290) disclosed financial relationships between the organizations producing the guidelines and biomedical companies. In the survey responses, 60 organizations reported the procedures that they included in their conflict of interest policies (158 guidelines): guidelines produced by organizations reporting more comprehensive conflict of interest policies (per additional procedure, range 5-17) included fewer positive (rate ratio [RR] 0.91, 95% CI 0.86-0.95) and more negative (RR 1.32, 95% CI 1.09-1.60) recommendations regarding patented biomedical products. The clinical practice guidelines produced by organizations reporting more comprehensive conflict of interest policies were also more likely to include disclosure statements for direct funding sources (odds ratio [OR] 1.31, 95% CI 1.10-1.56) and financial relationships of guideline committee members (OR 1.36, 95% CI 1.09-1.79), but not financial relationships of the organizations (0 disclosures). Limitations of the study include the use of the National Guideline Clearinghouse as the single source of clinical practice guidelines and the self-report of survey responses and organizations' website postings. Conclusions: Financial relationships between organizations that produce clinical practice guidelines and biomedical companies are common and infrequently disclosed in guidelines. Our study highlights the need for an effective policy to manage organizational conflicts of interest and disclosure of financial relationships.
Article
Full-text available
Conflicts of interest held by researchers remain a focus of attention in clinical research. Biases related to these relationships have the potential to directly impact the quality of healthcare by influencing decision-making, yet conflicts of interest remain under-reported, inconsistently described, and difficult to access. Initiatives aimed at improving the disclosure of researcher conflicts of interest are still in their infancy but represent a vital reform that must be addressed before potential biases associated with conflicts of interest can be mitigated, and trust in the impartiality of clinical evidence restored. In this review, we examine the prevalence of conflicts of interest, evidence of the effects that disclosed and undisclosed conflicts of interest have had on the reporting of clinical evidence, and the emerging approaches for improving the completeness and consistency of disclosures. Through this review of emerging technologies, we recognize a growing interest in publicly-accessible registries for researcher conflicts of interest, and propose five desiderata aimed at maximizing the value of such registries: mandates for ensuring that researchers keep their records up to date; transparent records that are made available to the public; interoperability to allow researchers, bibliographic databases, and institutions to interact with the registry; a consistent taxonomy for describing different classes of conflicts of interest, and the ability to automatically generate conflicts of interest statements for use in published articles.
Article
Full-text available
Strong opinions for or against the use of systematic reviews to inform policymaking have been published in the medical literature. The purpose of this paper was to examine whether funding sources and author financial conflicts of interest were associated with whether an opinion article was supportive or critical of the use of systematic reviews for policymaking. We examined the nature of the arguments within each article, the types of disclosures present, and whether these articles are being cited in the academic literature. We searched for articles that expressed opinions about the use of systematic reviews for policymaking. We included articles that presented opinions about the use of systematic reviews for policymaking and categorized each article as supportive or critical of such use. We extracted all arguments regarding the use of systematic reviews from each article and inductively coded each as internal or external validity argument, categorized disclosed funding sources, conflicts of interest, and article types, and systematically searched for undisclosed financial ties. We counted the number of times each article has been cited in the "Web of Science." We report descriptive statistics. Articles that were critical of the use of systematic reviews (n = 25) for policymaking had disclosed or undisclosed industry ties 2.3 times more often than articles that were supportive of the use (n = 34). We found that editorials, comments, letters, and perspectives lacked published disclosures nearly twice as often (60% v. 33%) as other types of articles. We also found that editorials, comments, letters, and perspectives were less frequently cited in the academic literature than other article types (median number of citations = 5 v. 19). It is important to consider whether an article has industry ties when evaluating the strength of the argument for or against the use of systematic reviews for policymaking. We found that journal conflict of interest disclosures are often inadequate, particularly for editorials, comments, letters, and perspectives and that these articles are being cited as evidence in the academic literature. Our results further suggest the need for more consistent and complete disclosure for all article types.
Article
Full-text available
Background: Financial ties between health professionals and industry may unduly influence professional judgments and some researchers have suggested that widening disease definitions may be one driver of over-diagnosis, bringing potentially unnecessary labeling and harm. We aimed to identify guidelines in which disease definitions were changed, to assess whether any proposed changes would increase the numbers of individuals considered to have the disease, whether potential harms of expanding disease definitions were investigated, and the extent of members' industry ties. Methods and findings: We undertook a cross-sectional study of the most recent publication between 2000 and 2013 from national and international guideline panels making decisions about definitions or diagnostic criteria for common conditions in the United States. We assessed whether proposed changes widened or narrowed disease definitions, rationales offered, mention of potential harms of those changes, and the nature and extent of disclosed ties between members and pharmaceutical or device companies. Of 16 publications on 14 common conditions, ten proposed changes widening and one narrowing definitions. For five, impact was unclear. Widening fell into three categories: creating "pre-disease"; lowering diagnostic thresholds; and proposing earlier or different diagnostic methods. Rationales included standardising diagnostic criteria and new evidence about risks for people previously considered to not have the disease. No publication included rigorous assessment of potential harms of proposed changes. Among 14 panels with disclosures, the average proportion of members with industry ties was 75%. Twelve were chaired by people with ties. For members with ties, the median number of companies to which they had ties was seven. Companies with ties to the highest proportions of members were active in the relevant therapeutic area. Limitations arise from reliance on only disclosed ties, and exclusion of conditions too broad to enable analysis of single panel publications. Conclusions: For the common conditions studied, a majority of panels proposed changes to disease definitions that increased the number of individuals considered to have the disease, none reported rigorous assessment of potential harms of that widening, and most had a majority of members disclosing financial ties to pharmaceutical companies. Please see later in the article for the Editors' Summary.
Article
Importance: Financial relationships between physicians and industry have influence on patient care. Therefore, organizations producing clinical practice guidelines (CPGs) must have policies limiting financial conflicts during guideline development. Objectives: To evaluate payments received by physician authors of otolaryngology CPGs, compare disclosure statements for accuracy, and investigate the extent to which the American Academy of Otolaryngology-Head and Neck Surgery complied with standards for guideline development from the Institute of Medicine (IOM). Design, setting, and participants: This cross-sectional analysis retrieved CPGs from the American Academy of Otolaryngology-Head and Neck Surgery Foundation that were published or revised from January 1, 2013, through December 31, 2015, by 49 authors. Data were retrieved from December 1 through 31, 2016. Industry payments received by authors were extracted using the Centers for Medicare & Medicaid Services Open Payments database. The values and types of these payments were then evaluated and used to determine whether self-reported disclosure statements were accurate and whether guidelines adhered to applicable IOM standards. Main outcomes and measures: The monetary amounts and types of payments received by physicians who author otolaryngology guidelines and the accuracy of disclosure statements. Results: Of the 49 physicians in this sample, 39 (80%) received an industry payment. Twenty-one authors (43%) accepted more than 1000;12(241000; 12 (24%), more than 10 000; 7 (14%), more than 50000;and2(450 000; and 2 (4%), more than 100 000. Mean (SD) financial payments amounted to 18431(18 431 (53 459) per physician. Total reimbursement for all authors was 995282.DisclosurestatementsdisagreedwiththeOpenPaymentsdatabasefor3authors,amountingtoapproximately995 282. Disclosure statements disagreed with the Open Payments database for 3 authors, amounting to approximately 20 000 among them. Of the 3 IOM standards assessed, only 1 was consistently enforced. Conclusions and relevance: Some CPG authors failed to fully disclose all financial conflicts of interest, and most guideline development panels and chairpersons had conflicts. In addition, adherence to IOM standards for guideline development was lacking. This study is relevant to CPG panels authoring recommendations, physicians implementing CPGs to guide patient care, and the organizations establishing policies for guideline development.
Article
Background: Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical-industry sponsored studies are more often favorable to the sponsor's product compared with studies with other sources of sponsorship. A similar association between sponsorship and outcomes have been found for device studies, but the body of evidence is not as strong as for sponsorship of drug studies. This review is an update of a previous Cochrane review and includes empirical studies on the association between sponsorship and research outcome. Objectives: To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. Search methods: In this update we searched MEDLINE (2010 to February 2015), Embase (2010 to February 2015), the Cochrane Methodology Register (2015, Issue 2) and Web of Science (June 2015). In addition, we searched reference lists of included papers, previous systematic reviews and author files. Selection criteria: Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions. Data collection and analysis: Two assessors screened abstracts and identified and included relevant papers. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals (CIs)). Main results: Twenty-seven new papers were included in this update and in total the review contains 75 included papers. Industry sponsored studies more often had favorable efficacy results, RR: 1.27 (95% CI: 1.17 to 1.37) (25 papers) (moderate quality evidence), similar harms results RR: 1.37 (95% CI: 0.64 to 2.93) (four papers) (very low quality evidence) and more often favorable conclusions RR: 1.34 (95% CI: 1.19 to 1.51) (29 papers) (low quality evidence) compared with non-industry sponsored studies. Nineteen papers reported on sponsorship and efficacy effect size, but could not be pooled due to differences in their reporting of data and the results were heterogeneous. We did not find a difference between drug and device studies in the association between sponsorship and conclusions (test for interaction, P = 0.98) (four papers). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.25 (95% CI: 1.05 to 1.50) (13 papers), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.83 (95% CI: 0.70 to 0.98) (six papers). Authors' conclusions: Sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.
Article
Issues of financial and intellectual conflict of interest in clinical practice guidelines have raised increasing concern. Professional organizations have responded by more rigorous regulation of conflict of interest. Nevertheless, tension remains between the competing goals of optimizing guideline quality by using the experience and insight of experts and ensuring that financial and intellectual conflicts of interest do not influence recommendations. The executive committee of the American College of Chest Physicians' Antithrombotic Guidelines has developed a strategy comprising 3 innovative aspects to address this tension: First, place equal emphasis on intellectual and financial conflicts and provide explicit criteria for both; second, a methodologist without important conflicts of interest should have primary responsibility for each chapter; and third, experts with important financial or intellectual conflicts of interest can collect and interpret evidence, but only panel members without important conflicts can be involved in developing the recommendation for a specific question. These strategies may help to achieve the benefits of expert input without conflicts of interest influencing recommendations.