Corporate Influences on Science and Health-the Case of Spinal Cord Stimulation.

This Viewpoint discusses tactics by corporations to criticize scientific research that may be unfavorable to their industries, recently including the spinal cord stimulator industry.

Interactions between Australian cancer physicians and the pharmaceutical industry: a qualitative study.

OBJECTIVES: To understand how and why Australian cancer physicians interact with the pharmaceutical industry. DESIGN: Qualitative study using semistructured interviews, performed by a medical oncologist. Thematic analysis using a combination of deductive and inductive codes. SETTING: Given the evidence on industry influences on clinical practice and the importance to the market of oncology drugs, we sought to better understand cancer physicians' experiences. Practising consultant medical oncologists and clinical haematologists from four Australian states were interviewed over Zoom. PARTICIPANTS: 16 cancer physicians were interviewed between November 2021 and March 2022, from 37 invited (response rate 43%). Most were medical oncologists (n=12 of 16, 75%) and male (n=9 of 16, 56%). OUTCOME MEASURES: The analysis of all interviews was based on grounded theory. Transcripts were coded and then codes formed into themes with supporting quotes. The themes were then placed into categories, used to describe the broad areas into which the themes could be grouped. RESULTS: Six themes were identified that fell within two broad categories: cancer physicians' views and experiences of interactions and management of these interactions. Views and experiences included: the transactional nature of relationships, risks of research dependence, ethical challenges and varied attitudes based on interaction type. Management themes included: lack of useful guidance and reduced interactions during the COVID-19 pandemic. These led to an overarching seventh theme, on the desire for a 'middle road'. Cancer physicians identified the transactional nature of industry relationships and felt uncomfortable with several types of interactions, including those with sales representatives. Most wanted less contact with industry, and the forced separation that occurred with the COVID-19 pandemic was generally welcome. CONCLUSIONS: Cancer physicians may have difficulty balancing the perceived need to interact with industry in modern cancer care while maintaining distance to minimise conflicts of interest. Further research is needed to assess management strategies in this area.

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.

Australian Cancer Physicians and the Pharmaceutical Industry: A Survey of Attitudes and Interactions.

PURPOSE: Interactions between cancer physicians and the pharmaceutical industry may create conflicts of interest that can adversely affect patient care. We aimed to survey cancer physicians regarding their attitudes toward and interactions with industry. METHODS: We surveyed Australian cancer physicians between December 2020 and February 2021, questioning how often they interacted with industry and their attitudes toward this. We also assessed factors associated with accepting payments from industry and the amount received, and opinions on policies and industry influence. We used logistic and linear regression to examine links between attitudes and behaviors. RESULTS: There were 116 responses (94 complete). Almost half (n = 53 of 115, 46.1%) felt that there was a positive relationship between cancer physicians and industry. Most (n = 79 of 104, 76.0%) interacted with industry at least once a month, and 67.7% (n = 63 of 93) had received nonresearch payments from industry previously, with a median value of 2,000 Australian dollars over 1 year. Most respondents believed that interactions could influence prescribing while simultaneously denying influence on their own prescribing (n = 66 of 94, 70.2%). Those who judged general sales representative interactions (odds ratio [OR] 9.37 [95% CI, 1.05 to 83.41], P = .045) or clinician sponsorship (OR 3.22 [95% CI, 1.01 to 10.30], P = .049) to be more acceptable also met with sales representatives more frequently. Physicians were more likely to accept industry payments when they deemed sponsorship of clinicians for conferences (OR 10.55 [95% CI, 2.33 to 47.89], P = .002) or honoraria for advisory board membership more acceptable (OR 3.91 [95% CI, 1.04 to 14.74], P = .04) or when they had higher belief in industry influence over own prescribing (OR 25.51 [95% CI, 2.70 to 241.45], P = .005). CONCLUSION: Australian cancer physicians interact with industry frequently, and those who feel positive about these interactions are likely to do so more often. More research is needed to understand the motivations behind these interactions.

Assessing the quality of evidence in studies estimating prevalence of exposure to occupational risk factors: The QoE-SPEO approach applied in the systematic reviews from the WHO/ILO Joint Estimates of the Work-related burden of disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) have produced the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). For these, systematic reviews of studies estimating the prevalence of exposure to selected occupational risk factors have been conducted to provide input data for estimations of the number of exposed workers. A critical part of systematic review methodology is to assess the quality of evidence across studies. In this article, we present the approach applied in these WHO/ILO systematic reviews for performing such assessments on studies of prevalence of exposure. It is called the Quality of Evidence in Studies estimating Prevalence of Exposure to Occupational risk factors (QoE-SPEO) approach. We describe QoE-SPEO's development to date, demonstrate its feasibility reporting results from pilot testing and case studies, note its strengths and limitations, and suggest how QoE-SPEO should be tested and developed further. METHODS: Following a comprehensive literature review, and using expert opinion, selected existing quality of evidence assessment approaches used in environmental and occupational health were reviewed and analysed for their relevance to prevalence studies. Relevant steps and components from the existing approaches were adopted or adapted for QoE-SPEO. New steps and components were developed. We elicited feedback from other systematic review methodologists and exposure scientists and reached consensus on the QoE-SPEO approach. Ten individual experts pilot-tested QoE-SPEO. To assess inter-rater agreement, we counted ratings of expected (actual and non-spurious) heterogeneity and quality of evidence and calculated a raw measure of agreement (Pi) between individual raters and rater teams for the downgrade domains. Pi ranged between 0.00 (no two pilot testers selected the same rating) and 1.00 (all pilot testers selected the same rating). Case studies were conducted of experiences of QoE-SPEO's use in two WHO/ILO systematic reviews. RESULTS: We found no existing quality of evidence assessment approach for occupational exposure prevalence studies. We identified three relevant, existing approaches for environmental and occupational health studies of the effect of exposures. Assessments using QoE-SPEO comprise three steps: (1) judge the level of expected heterogeneity (defined as non-spurious variability that can be expected in exposure prevalence, within or between individual persons, because exposure may change over space and/or time), (2) assess downgrade domains, and (3) reach a final rating on the quality of evidence. Assessments are conducted using the same five downgrade domains as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach: (a) risk of bias, (b) indirectness, (c) inconsistency, (d) imprecision, and (e) publication bias. For downgrade domains (c) and (d), the assessment varies depending on the level of expected heterogeneity. There are no upgrade domains. The QoE-SPEO's ratings are "very low", "low", "moderate", and "high". To arrive at a final decision on the overall quality of evidence, the assessor starts at "high" quality of evidence and for each domain downgrades by one or two levels for serious concerns or very serious concerns, respectively. In pilot tests, there was reasonable agreement in ratings for expected heterogeneity; 70% of raters selected the same rating. Inter-rater agreement ranged considerably between downgrade domains, both for individual rater pairs (range Pi: 0.36-1.00) and rater teams (0.20-1.00). Sparse data prevented rigorous assessment of inter-rater agreement in quality of evidence ratings. CONCLUSIONS: We present QoE-SPEO as an approach for assessing quality of evidence in prevalence studies of exposure to occupational risk factors. It has been developed to its current version (as presented here), has undergone pilot testing, and was applied in the systematic reviews for the WHO/ILO Joint Estimates. While the approach requires further testing and development, it makes steps towards filling an identified gap, and progress made so far can be used to inform future work in this area.

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.

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.

Strengthening the incentives for responsible research practices in Australian health and medical research funding.

BACKGROUND: Australian health and medical research funders support substantial research efforts, and incentives within grant funding schemes influence researcher behaviour. We aimed to determine to what extent Australian health and medical funders incentivise responsible research practices. METHODS: We conducted an audit of instructions from research grant and fellowship schemes. Eight national research grants and fellowships were purposively sampled to select schemes that awarded the largest amount of funds. The funding scheme instructions were assessed against 9 criteria to determine to what extent they incentivised these responsible research and reporting practices: (1) publicly register study protocols before starting data collection, (2) register analysis protocols before starting data analysis, (3) make study data openly available, (4) make analysis code openly available, (5) make research materials openly available, (6) discourage use of publication metrics, (7) conduct quality research (e.g. adhere to reporting guidelines), (8) collaborate with a statistician, and (9) adhere to other responsible research practices. Each criterion was answered using one of the following responses: "Instructed", "Encouraged", or "No mention". RESULTS: Across the 8 schemes from 5 funders, applicants were instructed or encouraged to address a median of 4 (range 0 to 5) of the 9 criteria. Three criteria received no mention in any scheme (register analysis protocols, make analysis code open, collaborate with a statistician). Importantly, most incentives did not seem strong as applicants were only instructed to register study protocols, discourage use of publication metrics and conduct quality research. Other criteria were encouraged but were not required. CONCLUSIONS: Funders could strengthen the incentives for responsible research practices by requiring grant and fellowship applicants to implement these practices in their proposals. Administering institutions could be required to implement these practices to be eligible for funding. Strongly rewarding researchers for implementing robust research practices could lead to sustained improvements in the quality of health and medical research.

Assessment of the Methods Used to Develop Vitamin D and Calcium Recommendations-A Systematic Review of Bone Health Guidelines.

BACKGROUND: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. METHODS: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development; and, identified types identified types of evidence underpinning the recommendations. RESULTS: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9-12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editorials were used to underpin the recommendations. CONCLUSIONS: There is considerable variability in vitamin D and calcium recommendations and in guideline development methods in bone health guidelines. Effort is required to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin nutrition recommendations in evidence-based guidelines on bone health.

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.

"It's Not Smooth Sailing": Bridging the Gap Between Methods and Content Expertise in Public Health Guideline Development.

BACKGROUND: The development of reliable, high quality health-related guidelines depends on explicit and transparent processes, methods aimed at minimising risks of bias and the inclusion of all relevant expertise and perspectives. While the methodological aspects of guidelines have been a focus to improve their quality, less is known about the social processes involved, for example, how guideline group members interact and communicate with one another, and how the evidence is considered in informing recommendations. With this in in mind, we aimed to empirically examine the perspectives and experiences of the key participants involved in developing public health guidelines for the Australian National Health and Medical Research Council (NHMRC). DESIGN: This study was conducted using constructivist grounded theory as described by Charmaz, which informed our sampling, data collection, coding and analysis of interviews with key participants involved in developing public health guidelines. SETTING: Australian public health guidelines commissioned by the NHMRC. PARTICIPANTS: Twenty experts that were involved in Australian NHMRC public health guideline development, including working committee members with content topic expertise (n=16) and members of evidence review groups responsible for evaluating the evidence (n=4). RESULTS: Public health guideline development in Australia is a divided process. The division is driven by 3 related factors: the divergent disciplinary background and expertise that each group brings to the process; the methodological limitations of the framework, inherited from clinical medicine, that is used to assess the evidence; and barriers to communication between content experts and evidence reviewers around respective roles and methodological limitations. CONCLUSION: Our findings suggest several improvements for a more functional and unified guideline development process: greater education of the working committee on the methodological process employed to evaluate evidence, improved communication on the role of the evidence review groups and better facilitation of the process so that the evidence review groups feel their contribution is valued.

Reporting of financial conflicts of interest in meta-analyses of drug trials published in high-impact medical journals: comparison of results from 2017 to 2018 and 2009.

BACKGROUND: A previous study found that 2 of 29 (6.9%) meta-analyses published in high-impact journals in 2009 reported included drug trials' funding sources, and none reported trial authors' financial conflicts of interest (FCOIs) or industry employment. It is not known if reporting has improved since 2009. Our objectives were to (1) investigate the extent to which pharmaceutical industry funding and author-industry FCOIs and employment from included drug trials are reported in meta-analyses published in high-impact journals and (2) compare current reporting with results from 2009. METHODS: We searched PubMed (January 2017-October 2018) for systematic reviews with meta-analyses including ≥ 2 randomized controlled trials (RCTs) of patented drugs. We included 3 meta-analyses published January 2017-October 2018 from each of 4 high-impact general medicine journals, high-impact journals from 5 specialty areas, and the Cochrane Database of Systematic Reviews, as in the previous study. RESULTS: Among 29 meta-analyses reviewed, 13 of 29 (44.8%) reported the funding source of included trials compared to 2 of 29 (6.9%) in 2009, a difference of 37.9% (95% confidence interval, 15.7 to 56.3%); this included 7 of 11 (63.6%) from general medicine journals, 3 of 15 (20.0%) from specialty medicine journals, and 3 of 3 (100%) Cochrane reviews. Only 2 of 29 meta-analyses (6.9%) reported trial author FCOIs, and none reported trial author-industry employment. PROTOCOL PUBLICATION: A protocol was uploaded to the Open Science Framework prior to initiating the study. https://osf.io/8xt5p/ LIMITATIONS: We examined only a relatively small number of meta-analyses from selected high-impact journals and compared results to a similarly small sample from an earlier time period. CONCLUSIONS: Reporting of drug trial sponsorship and author FCOIs in meta-analyses published in high-impact journals has increased since 2009 but is still suboptimal. Standards on reporting of trial funding described in the forthcoming revised PRISMA statement should be adapted and enforced by journals to improve reporting.

Correction: Relationship between Research Outcomes and Risk of Bias, Study Sponsorship, and Author Financial Conflicts of Interest in Reviews of the Effects of Artificially Sweetened Beverages on Weight Outcomes: A Systematic Review of Reviews.

[This corrects the article DOI: 10.1371/journal.pone.0162198.].