“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

The effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer: A systematic review and meta-analysis 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) are the producers of the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). Welding fumes have been classified as carcinogenic to humans (Group 1) by the WHO International Agency for Research on Cancer (IARC) in IARC Monograph 118; this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus, and lung cancer attributable to occupational exposure to welding fumes, to inform the development of WHO/ILO Joint Estimates on this burden of disease (if considered feasible). Objectives: We aimed to systematically review and meta-analyse estimates of the effect of any (or high) occupational exposure to welding fumes, compared with no (or low) occupational exposure to welding fumes, on trachea, bronchus, and lung cancer (three outcomes: prevalence, incidence, and mortality). Data sources: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CENTRAL and CISDOC. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. Study eligibility and criteria: We included working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but excluded children (<15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies, and other non-randomized intervention studies with an estimate of the effect of any (or high) occupational exposure to welding fumes, compared with occupational exposure to no (or low) welding fumes, on trachea, bronchus, and lung cancer (prevalence, incidence, and mortality). Study appraisal and synthesis methods: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. If studies reported odds ratios, these were converted to risk ratios (RRs). We combined all RRs using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence, and strength of evidence, using the Navigation Guide tools and approaches adapted to this project. Subgroup (e.g., by WHO region and sex) and sensitivity analyses (e.g., studies judged to be of “high”/“probably high” risk of bias compared with “low”/“probably low” risk of bias) were conducted. Results: Forty-one records from 40 studies (29 case control studies and 11 cohort studies) met the inclusion criteria, comprising over 1,265,512 participants (≥22,761 females) in 21 countries in three WHO regions (Region of the Americas, European Region, and Western Pacific Region). The exposure and outcome were generally assessed by job title or self-report, and medical or administrative records, respectively. Across included studies, risk of bias was overall generally probably low/low, with risk judged high or probably high for several studies in the domains for misclassification bias and confounding.Our search identified no evidence on the outcome of having trachea, bronchus, and lung cancer (prevalence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk of acquiring trachea, bronchus, and lung cancer (incidence) by an estimated 48 % (RR 1.48, 95 % confidence interval [CI] 1.29–1.70, 23 studies, 57,931 participants, I2 24 %; moderate quality of evidence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk dying from trachea, bronchus, and lung cancer (mortality) by an estimated 27 % (RR 1.27, 95 % CI 1.04–1.56, 3 studies, 8,686 participants, I2 0 %; low quality of evidence). Our subgroup analyses found no evidence for difference by WHO region and sex. Sensitivity analyses supported the main analyses. Conclusions: Overall, for incidence and mortality of trachea, bronchus, and lung cancer, we judged the existing body of evidence for human data as “sufficient evidence of harmfulness” and “limited evidence of harmfulness”, respectively. Occupational exposure to welding fumes increased the risk of acquiring and dying from trachea, bronchus, and lung cancer. Producing estimates for the burden of trachea, bronchus, and lung cancer attributable to any (or high) occupational exposure to welding fumes appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates. Protocol identifier: https://doi.org/10.1016/j.envint.2020.106089

Reducing Bias in Public Health Guidelines

Background and Objectives Bias in research and the methods used for developing public health guidelines may put the public’s health at risk. This dissertation explores three possible sources of influence on the recommendations made in public health guidelines: • Commercial Influences on Nutrition Research: Primary research studies and systematic reviews form the evidence base for dietary guidelines. The association between funding sources and the outcomes of nutrition studies was therefore explored; • Methods Used for Public Health Guideline Development: Heterogenous methodologies used in the development of public health guidelines may lead to conflicting recommendations. I conducted a systematic analysis of the methods used in their development; • Social Influences on Public Health Guideline Development: The interactions within guideline groups may be a significant influence on the final recommendations made. I aimed to understand the experiences of the participants involved in developing public health guidelines. Methods My methods included: 1) Meta-analysis and systematic review to measure bias in primary nutrition research; 2) Content analysis to understand the methods used in synthesising evidence for public health guidance development; and 3) Qualitative analysis of interviews to understand social influences on guideline development. Results My major findings were: I found an association with industry sponsorship with the outcomes of studies, even when controlling for the internal validity between the studies; I established heterogenous methodologies are being used by organisations that conduct hazard identification and risk assessment; and I identified that the public health guideline process in Australia is a divided one. Conclusions Through greater transparency of funding practices, the development of nutrition study registries and improvements in risk of bias tools used to evaluate the evidence, industry influence on the outcomes of nutrition studies relevant to dietary guidelines can be accounted for. Further, the use of standardised, transparent methodological processes and collaboration between systematic review teams and guideline groups will lead to increased comparability and validity of guidelines and ensure that the recommendations made from them will protect the public’s health

Associations between industry involvement and study characteristics at the time of trial registration in biomedical research

Background Commercial or industry funding is associated with outcomes that favour the study funder in published studies, across various areas of research. However, it is currently unclear whether there are differences between trials with and without industry involvement at the stage of trial registration. Objective To determine whether industry involvement (industry sponsorship, funding, or collaboration) is associated with trial characteristics at the time of trial registration. Methods We conducted a cross-sectional analysis of all interventional studies registered on the Australian New Zealand Clinical Trials Registry in 2017 and classified them by industry involvement. We analysed whether there were differences in study characteristics (including type of control, sample size, study phase, randomisation, registration timing, and purpose of study) by industry involvement. Results Industry involvement was reported by 21% of the 1,433 included trials. Only 40% of trials with industry involvement used an active control compared to 58% of non-industry trials (OR = 0.49, 95%CI = 0.38 to 0.63, p < .001), and industry trials reported smaller sample sizes (Median(IQR)industry = 45(24–100), Median(IQR)non-industry = 70(35–160), Mean Difference = -153, 95% CI = -233 to -75, p < .001). Industry trials were more likely to be earlier phase trials (Χ2(df) = 71.46(4), p < .001). There was no difference in use of randomisation between industry (70%) and non-industry trials (73%) (OR = 0.88, 95%CI = 0.67–1.20, p = .38). Eighty-three percent of industry trials compared to 70% of non-industry trials were prospectively registered (OR = 2.02, 95%CI = 1.47–2.82, p < .001). Industry trials were more likely to assess treatment (85%), rather than prevention, education or diagnosis compared to non-industry trials (64%) (OR = 3.02, 95%CI = 2.17–4.32, p < .001). Conclusion The current study gives insight into differences in trial characteristics by industry involvement at registration stage. There was a reduced use of active controls in trials with industry involvement which has previously been proposed as a mechanism behind more favourable results. Non-industry funders and sponsors are crucial to ensure research addresses not only treatments, but also prevention, diagnosis and education questions

Associations between industry involvement and study characteristics at the time of trial registration in biomedical research.

BACKGROUND:Commercial or industry funding is associated with outcomes that favour the study funder in published studies, across various areas of research. However, it is currently unclear whether there are differences between trials with and without industry involvement at the stage of trial registration. OBJECTIVE:To determine whether industry involvement (industry sponsorship, funding, or collaboration) is associated with trial characteristics at the time of trial registration. METHODS:We conducted a cross-sectional analysis of all interventional studies registered on the Australian New Zealand Clinical Trials Registry in 2017 and classified them by industry involvement. We analysed whether there were differences in study characteristics (including type of control, sample size, study phase, randomisation, registration timing, and purpose of study) by industry involvement. RESULTS:Industry involvement was reported by 21% of the 1,433 included trials. Only 40% of trials with industry involvement used an active control compared to 58% of non-industry trials (OR = 0.49, 95%CI = 0.38 to 0.63, p < .001), and industry trials reported smaller sample sizes (Median(IQR)industry = 45(24-100), Median(IQR)non-industry = 70(35-160), Mean Difference = -153, 95% CI = -233 to -75, p < .001). Industry trials were more likely to be earlier phase trials (Χ2(df) = 71.46(4), p < .001). There was no difference in use of randomisation between industry (70%) and non-industry trials (73%) (OR = 0.88, 95%CI = 0.67-1.20, p = .38). Eighty-three percent of industry trials compared to 70% of non-industry trials were prospectively registered (OR = 2.02, 95%CI = 1.47-2.82, p < .001). Industry trials were more likely to assess treatment (85%), rather than prevention, education or diagnosis compared to non-industry trials (64%) (OR = 3.02, 95%CI = 2.17-4.32, p < .001). CONCLUSION:The current study gives insight into differences in trial characteristics by industry involvement at registration stage. There was a reduced use of active controls in trials with industry involvement which has previously been proposed as a mechanism behind more favourable results. Non-industry funders and sponsors are crucial to ensure research addresses not only treatments, but also prevention, diagnosis and education questions

Evidence-to-decision frameworks: a review and analysis to inform decision-making for environmental health interventions.

BackgroundEvidence-to-decision (EtD) frameworks provide a structured and transparent approach for groups of experts to use when formulating recommendations or making decisions. While extensively used for clinical and public health recommendations, EtD frameworks are not in widespread use in environmental health. This review sought to identify, compare and contrast key EtD frameworks for decisions on interventions used in clinical medicine, public health or environmental health. This information can be used to develop an EtD framework suitable for formulating recommendations for interventions in environmental health.MethodsWe identified a convenience sample of EtD frameworks used by a range of organizations. We searched Medline for systematic reviews of frameworks. We summarized the decision criteria in the selected frameworks and reviews in a qualitative manner.FindingsFourteen organizations provided 18 EtD frameworks; most frameworks focused on clinical medicine or public health interventions; four focused on environmental health and three on economic considerations. Harms of interventions were examined in all frameworks and benefits in all but one. Other criteria included certainty of the body of evidence (15 frameworks), resource considerations (15), feasibility (13), equity (12), values (11), acceptability (11), and human rights (2). There was variation in how specific criteria were defined. The five identified systematic reviews reported a similar spectrum of EtD criteria.InterpretationThe EtD frameworks examined encompassed similar criteria, with tailoring to specific audience needs. Existing frameworks are a useful starting point for development of one tailored to decision-making in environmental health.FunderJPB Foundation