Interactions with the pharmaceutical industry and the practice, knowledge and beliefs of medical oncologists and clinical haematologists: a systematic review.

BACKGROUND: No previous review has assessed the extent and effect of industry interactions on medical oncologists and haematologists specifically. METHODS: A systematic review investigated interactions with the pharmaceutical industry and how these might affect the clinical practice, knowledge and beliefs of cancer physicians. MEDLINE, Embase, PsycINFO and Web of Science Core Collection databases were searched from inception to February 2021. RESULTS: Twenty-nine cross-sectional and two cohort studies met the inclusion criteria. These were classified into three categories of investigation: (1) extent of exposure to industry for cancer physicians as whole (n = 11); (2) financial ties among influential cancer physicians specifically (n = 11) and (3) associations between industry exposure and prescribing (n = 9). Cancer physicians frequently receive payments from or maintain financial ties with industry, at a prevalence of up to 63% in the United States (US) and 70.6% in Japan. Among influential clinicians, 86% of US and 78% of Japanese oncology guidelines authors receive payments. Payments were associated with either a neutral or negative influence on the quality of prescribing practice. Limited evidence suggests oncologists believe education by industry could lead to unconscious bias. CONCLUSIONS: There is substantial evidence of frequent relationships between cancer physicians and the pharmaceutical industry in a range of high-income countries. More research is needed on clinical implications for patients and better management of these relationships. REGISTRATION: PROSPERO identification number CRD42020143353.

Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1].

BACKGROUND: In August 2021, we published in Environmental Health a Toolkit for detecting misused epidemiological methods with the goal of providing an organizational framework for transparently evaluating epidemiological studies, a body of evidence, and resultant conclusions. Tsuda et al., the first group to utilize the Toolkit in a systematic fashion, have offered suggestions for its modification. MAIN BODY: Among the suggested modifications made by Tsuda et al., we agree that rearrangement of Part A of the Toolkit to reflect the sequence of the epidemiological study process would facilitate its usefulness. Expansion or adaptation of the Toolkit to other disciplines would be valuable but would require the input of discipline-specific expertise. We caution against using the sections of the Toolkit to produce a tally or cumulative score, because none of the items are weighted as to importance or impact. Rather, we suggest a visual representation of how a study meets the Toolkit items, such as the heat maps used to present risk of bias criteria for studies included in Cochrane reviews. We suggest that the Toolkit be incorporated in the sub-specialty known as "forensic epidemiology," as well as in graduate training curricula, continuing education programs, and conferences, with the recognition that it is an extension of widely accepted ethics guidelines for epidemiological research. CONCLUSION: We welcome feedback from the research community about ways to strengthen the Toolkit as it is applied to a broader assemblage of research studies and disciplines, contributing to its value as a living tool/instrument. The application of the Toolkit by Tsuda et al. exemplifies the usefulness of this framework for transparently evaluating, in a systematic way, epidemiological research, conclusions relating to causation, and policy decisions. POSTSCRIPT: We note that our Toolkit has, most recently, inspired authors with discipline-specific expertise in the field of Conservation Biology to adapt it for use in the Biological Sciences.

Disclosure of funding sources and conflicts of interest in evidence underpinning vitamin D and calcium recommendations in bone health guidelines.

OBJECTIVE: The present study aims to examine the relationship between study funding sources, author conflicts of interest (COI) and conclusions in studies supporting vitamin D and Ca intake cited in bone health guideline recommendations. DESIGN: Cross-sectional. SETTING: Forty-seven global bone health guidelines with vitamin D and/or Ca recommendations for adults aged 40 years and above. PARTICIPANTS: The evidence cited to support the recommendations was extracted by two independent reviewers and classified by type of recommendation, article characteristics, study design, types of funding sources and conflict of interest (COI) disclosure and direction of study conclusions. RESULTS: Of 156 articles cited to support the bone health recommendations, 120 (77 %) disclosed a funding source, and 43 (28 %) declared that at least one author had a COI. Compared with articles with non-commercial or no funding source, those funded by commercial sponsors tended to have a study conclusion favourable towards vitamin D/Ca (relative risk (95 % CI): 1·32 (0·94, 1·87), P = 0·16), but the association was not statistically significant (Fisher's exact test). Compared to those with a COI disclosure statement, articles with missing or unclear COI disclosure were more likely to have favourable conclusions (1·56 (1·05, 2·31), P = 0·017) (Fisher's exact test). CONCLUSION: In the evidence underpinning a sample of global bone health guidelines, COI disclosure was low and studies with missing or unclear COI disclosures were more likely to have favourable study conclusions than those with disclosures, suggesting a need for greater transparency of COI in bone health guidelines.

Toolkit for detecting misused epidemiological methods.

BACKGROUND: Critical knowledge of what we know about health and disease, risk factors, causation, prevention, and treatment, derives from epidemiology. Unfortunately, its methods and language can be misused and improperly applied. A repertoire of methods, techniques, arguments, and tactics are used by some people to manipulate science, usually in the service of powerful interests, and particularly those with a financial stake related to toxic agents. Such interests work to foment uncertainty, cast doubt, and mislead decision makers by seeding confusion about cause-and-effect relating to population health. We have compiled a toolkit of the methods used by those whose interests are not aligned with the public health sciences. Professional epidemiologists, as well as those who rely on their work, will thereby be more readily equipped to detect bias and flaws resulting from financial conflict-of-interest, improper study design, data collection, analysis, or interpretation, bringing greater clarity-not only to the advancement of knowledge, but, more immediately, to policy debates. METHODS: The summary of techniques used to manipulate epidemiological findings, compiled as part of the 2020 Position Statement of the International Network for Epidemiology in Policy (INEP) entitled Conflict-of-Interest and Disclosure in Epidemiology, has been expanded and further elucidated in this commentary. RESULTS: Some level of uncertainty is inherent in science. However, corrupted and incomplete literature contributes to confuse, foment further uncertainty, and cast doubt about the evidence under consideration. Confusion delays scientific advancement and leads to the inability of policymakers to make changes that, if enacted, would-supported by the body of valid evidence-protect, maintain, and improve public health. An accessible toolkit is provided that brings attention to the misuse of the methods of epidemiology. Its usefulness is as a compendium of what those trained in epidemiology, as well as those reviewing epidemiological studies, should identify methodologically when assessing the transparency and validity of any epidemiological inquiry, evaluation, or argument. The problems resulting from financial conflicting interests and the misuse of scientific methods, in conjunction with the strategies that can be used to safeguard public health against them, apply not only to epidemiologists, but also to other public health professionals. CONCLUSIONS: This novel toolkit is for use in protecting the public. It is provided to assist public health professionals as gatekeepers of their respective specialty and subspecialty disciplines whose mission includes protecting, maintaining, and improving the public's health. It is intended to serve our roles as educators, reviewers, and researchers.

Industry payments to Australian medical oncologists and clinical haematologists: a cross-sectional analysis of publicly available disclosures.

BACKGROUND: Payments to medical oncologists and clinical haematologists can negatively affect prescribing practice, but the extent of payments to these specialists is unknown in Australia. AIMS: To analyse the extent of payments from the pharmaceutical industry to Australian cancer physicians as reported during the first collated period of the Disclosure Australia website. METHODS: We performed a retrospective, cross-sectional analysis of payments made from November 2018 to April 2019, using a file downloaded from the Disclosure Australia website. We checked the names of listed medical practitioners against Medical Board of Australia records to assign specialties. The number of medical oncologists, clinical haematologists, other specialist physicians and non-specialist physician medical practitioners was calculated, along with the payments to each of these groups. RESULTS: A total of A$7 332 407 was paid to 2775 medical practitioners. Of these, 236 were medical oncologists, 189 were haematologists and 1145 were other specialist physicians. This represents 31.7% of Australian medical oncologists and 30.9% of Australian haematologists, compared with 11.7% of all other specialist physicians and 1.1% of all other non-specialist physician medical practitioners. Medical oncologists received significantly higher payments (median A$2131.26) than other specialist physicians (median A$1376.00, 2-tailed P = 0.004) and other medical practitioners (median A$709.00, 2-tailed P < 0.001), while haematologists received significantly higher payments (median A$1519.95) than other medical practitioners (2-tailed P < 0.001), but similar payments to other specialist physicians (2-tailed P = 0.08). CONCLUSIONS: Australian cancer physicians receive payments at a higher proportional frequency and in greater dollar amounts than other specialist physicians and other medical practitioners in general.

Why Having a (Nonfinancial) Interest Is Not a Conflict of Interest.

A current debate about conflicts of interest related to biomedical research is to question whether the focus on financial conflicts of interest overshadows "nonfinancial" interests that could put scientific judgment at equal or greater risk of bias. There is substantial evidence that financial conflicts of interest such as commercial sponsorship of research and investigators lead to systematic biases in scientific research at all stages of the research process. Conflation of "conflicts of interest" with "interests" in general serves to muddy the waters about how to manage conflicts of interest. We call for heightened disclosure of conflicts of interest and policy action beyond disclosure as the sole management strategy. We propose a different strategy to manage interests more broadly to ensure fair representation and accountability.

How can the integrity of occupational and environmental health research be maintained in the presence of conflicting interests?

BACKGROUND: The sciences, and especially the research subspecialties of occupational and environmental health, are being misused. The misuse serves to interfere with the advancement of policies that depend on rational evidence needed for policies to protect public health. METHODS: We selectively surveyed the independent scientific literature. In addition, the efforts of respected international professional organizations of scientists whose focus is on maintaining and improving public health have been considered. This commentary is unique in assembling not only the factual basis for sounding alarms about significant bias in occupational and environmental health research, but also about the manipulative mechanisms used, and, in turn, the methods needed to keep science honest. RESULTS: Scientific integrity is based on the principle that research is conducted as objectively as possible; it cannot be compromised by special interests whose primary goals are neither to seek truth nor to protect human health. Evidence demonstrates a significant risk of bias in research reports sponsored by financial interests. Practices of corporate malfeasance include the orchestrated contamination of editorial boards of peer-reviewed scientific journals with industry apologists; interference with activities of national regulatory bodies and international review panels engaged in safeguarding occupational and public health; constructing roadblocks by capitalizing on uncertainty to undermine scientific consensus for much-needed government regulation of carcinogenic, endocrine-disrupting and/or immunotoxic agents; promoting "causation" criteria that lack foundation and effectively block workers' access to legal remedies for harms from occupational exposures resulting in morbidity and premature mortality; and, violating standards of professional conduct by seducing reputable scientists with financial incentives that make them beholden to corporate agendas. CONCLUSIONS: Well-orchestrated assaults on science continue unabated and must now be met head-on. Success could be achieved by promoting and protecting the integrity of research. Furthermore, avoiding influence by conflicted corporate affiliates in occupational and public health regulations is needed. Identifying, managing and, ideally, eliminating corporate influence on science and science policy are needed to protect research integrity. Protecting the public's health, preventing disease, and promoting well-being must be the unambiguous goals of research in occupational and environmental health.

Philip Morris International-funded 'Foundation for a Smoke-Free World': analysing its claims of independence.

The Foundation for a Smoke-Free World was launched in September 2017 with an announced 12-year funding commitment of $1 billion from Philip Morris International (PMI). The Foundation claims that its governing documents (certificate of incorporation, bylaws and a pledge agreement) ensure that it has an independent research agenda and stringent protections from conflicts of interest. We analysed the text of these governing documents. Their provisions have multiple loopholes, particularly regarding conflicts of interest. Further, these documents cannot substitute for other important documentation such as information about PMI's internal business case for investing $1 billion in the Foundation, an unwaivable conflict of interest policy, annual disclosure statements, copies of pre-Foundation establishment correspondence between key individuals, all signed contracts or salary information, none of which, as of July 2018, the Foundation has made publicly available. Even if these were released, however, it is problematic that the Foundation's fundamental purpose was decided on and its leader selected following a tobacco company-paid, privately negotiated arrangement with the Foundation's president. It cannot be regarded as independent.

Food industry sponsorship of academic research: investigating commercial bias in the research agenda.

OBJECTIVE: To identify scientific publications that result from food industry-funded projects on human health and to characterize their research topics to assess the potential for bias in the research agenda. DESIGN: Cross-sectional analysis.Setting/SubjectsFood industry-supported projects related to human health were identified from food company websites; publications resulting from the food industry-sponsored projects were identified through a PubMed search. RESULTS: Of ten companies analysed, only two (Coca-Cola and the Mars Center for Cocoa Health Science) provided a list of research projects with sufficient detail for analysis. Among the 204 publications resulting from thirty-seven disclosed research projects, the most common topic was physical activity (40·7 %), while highly processed foods were analysed in 10·8 % of the publications. Twenty-two publications (10·8 %) focused on research integrity or research methods. CONCLUSIONS: Publications resulting from Coca-Cola- and Mars-sponsored research appear to skew the evidence towards solutions that favour industry interests by focusing on food components that can be manipulated and marketed by food companies. These food industry-funded publications can also distract from nutrition as a health issue by diverting public and policy attention to physical activity. Shaping the debate around scientific methods can be another strategy that corporations use for their benefit to raise doubts about the methods used in non-industry sponsored research.

Study sponsorship and the nutrition research agenda: analysis of cohort studies examining the association between nutrition and obesity.

OBJECTIVE: To categorize the research topics covered by a sample of cohort studies exploring the association between nutrition and obesity; to describe their funding sources; and to explore the association between funding sources and research topics. DESIGN: Cross-sectional study. SUBJECTS: Cohort studies retrieved from MEDLINE and PubMed published between 2010 and 2016. RESULTS: One hundred and twenty-one studies were included. Funding source and conflicts of interest were disclosed in 95·0 and 90·1 % of the studies, respectively. Food industry sponsorship was disclosed in 8·3 % of the studies. Half of the studies analysed the consumption of a single food or food groups, 18·2 % included an analysis of dietary patterns and 17·4 % focused on specific nutrients. Highly processed foods were considered in 48·8 % of the studies and 27·3 % considered dietary behaviours (e.g. eating away from home). No statistically significant differences in research topics were observed between industry- and non-industry-funded studies. CONCLUSIONS: Cohort studies focused on more complex exposures (e.g. food or dietary patterns) rather than single nutrients. No significant differences in the research agenda by funding sources were observed. The analysis was limited by the low proportion of studies with disclosed food industry sponsorship.

Study sponsorship and the nutrition research agenda: analysis of randomized controlled trials included in systematic reviews of nutrition interventions to address obesity.

OBJECTIVE: To categorize the research topics covered by a sample of randomized controlled trials (RCT) included in systematic reviews of nutrition interventions to address obesity; to describe their funding sources; and to explore the association between funding sources and nutrition research topics. DESIGN: Cross-sectional study. SUBJECTS: RCT included in Cochrane Reviews of nutrition interventions to address obesity and/or overweight. RESULTS: Two hundred and thirteen RCT from seventeen Cochrane Reviews were included. Funding source and authors' conflicts of interest were disclosed in 82·6 and 29·6 % of the studies, respectively. RCT were more likely to test an intervention to manipulate nutrients in the context of reduced energy intake (44·2 % of studies) than food-level (11·3 %) and dietary pattern-level (0·9 %) interventions. Most of the food industry-sponsored studies focused on interventions involving manipulations of specific nutrients (66·7 %). Only 33·1 % of the industry-funded studies addressed dietary behaviours compared with 66·9 % of the non-industry-funded ones (P=0·002). The level of food processing was poorly considered across all funding sources. CONCLUSIONS: The predominance of RCT examining nutrient-specific questions could limit the public health relevance of rigorous evidence available for systematic reviews and dietary guidelines.

Marketing and the Most Trusted Profession: The Invisible Interactions Between Registered Nurses and Industry.

BACKGROUND: The mainstay for addressing conflicts of interest in health care is disclosure of personal financial ties to industry. However, this approach fails to capture the complexity of industry interactions that are built into clinical practice. Further, the policy climate focuses on physicians and traditional pharmaceutical marketing. OBJECTIVE: To describe industry activities targeted at registered nurses. DESIGN: Qualitative, ethnographic study conducted from January 2012 to October 2014. SETTING: Four acute care hospitals in a western U.S. city. PARTICIPANTS: A purposive sample of 72 participants with direct experience with industry, including staff nurses, administrators, and industry and supply chain professionals. MEASUREMENTS: Fieldwork, including observations (102 hours), semistructured in-depth interviews (n = 51), focus groups (n = 4), and documents analysis. RESULTS: Nurses' reported financial relationships with industry were similar to those reported by prescribers. However, nurses reported that their most significant interactions with industry occurred in daily practice. The current policy environment rendered these interactions invisible, leaving nurses with little guidance to ensure that the boundary between service and sales remained intact. LIMITATIONS: This study could not determine the frequency or prevalence of nurse-industry interactions. The sample is not representative. CONCLUSION: Nurse-industry interactions may be common and influential, but they remain invisible in the current policy climate. Although some aspects of these interactions may be beneficial, others may pose financial risks to hospitals or safety risks to patients. Disclosure strategies alone do not provide health professionals with adequate support to manage day-to-day interactions. Management of industry interactions must include guidance for nurses. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality; Canadian Institutes of Health Research; and University of California, San Francisco.

Tracing the Potential Flow of Consumer Data: A Network Analysis of Prominent Health and Fitness Apps.

BACKGROUND: A great deal of consumer data, collected actively through consumer reporting or passively through sensors, is shared among apps. Developers increasingly allow their programs to communicate with other apps, sensors, and Web-based services, which are promoted as features to potential users. However, health apps also routinely pose risks related to information leaks, information manipulation, and loss of information. There has been less investigation into the kinds of user data that developers are likely to collect, and who might have access to it. OBJECTIVE: We sought to describe how consumer data generated from mobile health apps might be distributed and reused. We also aimed to outline risks to individual privacy and security presented by this potential for aggregating and combining user data across apps. METHODS: We purposively sampled prominent health and fitness apps available in the United States, Canada, and Australia Google Play and iTunes app stores in November 2015. Two independent coders extracted data from app promotional materials on app and developer characteristics, and the developer-reported collection and sharing of user data. We conducted a descriptive analysis of app, developer, and user data collection characteristics. Using structural equivalence analysis, we conducted a network analysis of sampled apps' self-reported sharing of user-generated data. RESULTS: We included 297 unique apps published by 231 individual developers, which requested 58 different permissions (mean 7.95, SD 6.57). We grouped apps into 222 app families on the basis of shared ownership. Analysis of self-reported data sharing revealed a network of 359 app family nodes, with one connected central component of 210 app families (58.5%). Most (143/222, 64.4%) of the sampled app families did not report sharing any data and were therefore isolated from each other and from the core network. Fifteen app families assumed more central network positions as gatekeepers on the shortest paths that data would have to travel between other app families. CONCLUSIONS: This cross-sectional analysis highlights the possibilities for user data collection and potential paths that data is able to travel among a sample of prominent health and fitness apps. While individual apps may not collect personally identifiable information, app families and the partners with which they share data may be able to aggregate consumer data, thus achieving a much more comprehensive picture of the individual consumer. The organizations behind the centrally connected app families represent diverse industries, including apparel manufacturers and social media platforms that are not traditionally involved in health or fitness. This analysis highlights the potential for anticipated and voluntary but also possibly unanticipated and involuntary sharing of user data, validating privacy and security concerns in mobile health.

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.

BACKGROUND: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. METHODS: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. RESULTS: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. CONCLUSIONS: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.

Realist review of policy intervention studies aimed at reducing exposures to environmental hazards in the United States.

BACKGROUND: Exposure to pollution is a significant risk to human health. However few studies have attempted to identify the types of policy interventions that can reduce the health risks of pollution exposure in the United States. The study objective was to conduct a realist review of policy interventions conducted or aimed at reducing chemical exposures in humans or the environment where exposure was measured. METHODS: A systematic literature search identified published articles that assessed policy interventions using exposure data. Two coders independently extracted data from the studies, assessing methods, context, details of interventions, outcomes, and risks of bias. Data were analyzed iteratively and manually to identify the most effective and transferrable types of interventions. The reasons for variability in the success of different interventions were explored. RESULTS: The review found that regulatory interventions that eliminate point sources of pollution appeared to reduce exposure to environmental hazards. Regular monitoring to provide environmental and human exposure data helped assess compliance with the regulatory standards. Educational and economic interventions were less successful. CONCLUSIONS: Although some types of regulatory interventions appear to reduce exposures, our findings are limited by the nature of existing interventions, the weaknesses of the study designs used in the literature, and the lack of details on implementation. Information on contextual factors that influence implementation would assist with future reviews and could help identify effective interventions.