Systems for rating bodies of evidence used in systematic reviews of air pollution exposure and reproductive and children's health: a methodological survey.

BACKGROUND: Translating findings from systematic reviews assessing associations between environmental exposures and reproductive and children's health into policy recommendations requires valid and transparent evidence grading. METHODS: We aimed to evaluate systems for grading bodies of evidence used in systematic reviews of environmental exposures and reproductive/ children's health outcomes, by conducting a methodological survey of air pollution research, comprising a comprehensive search for and assessment of all relevant systematic reviews. To evaluate the frameworks used for rating the internal validity of primary studies and for grading bodies of evidence (multiple studies), we considered whether and how specific criteria or domains were operationalized to address reproductive/children's environmental health, e.g., whether the timing of exposure assessment was evaluated with regard to vulnerable developmental stages. RESULTS: Eighteen out of 177 (9.8%) systematic reviews used formal systems for rating the body of evidence; 15 distinct internal validity assessment tools for primary studies, and nine different grading systems for bodies of evidence were used, with multiple modifications applied to the cited approaches. The Newcastle Ottawa Scale (NOS) and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework, neither developed specifically for this field, were the most commonly used approaches for rating individual studies and bodies of evidence, respectively. Overall, the identified approaches were highly heterogeneous in both their comprehensiveness and their applicability to reproductive/children's environmental health research. CONCLUSION: Establishing the wider use of more appropriate evidence grading methods is instrumental both for strengthening systematic review methodologies, and for the effective development and implementation of environmental public health policies, particularly for protecting pregnant persons and children.

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.

An approach to quantifying the potential importance of residual confounding in systematic reviews of observational studies: A GRADE concept paper.

Small relative effect sizes are common in observational studies of exposure in environmental and public health. However, such effects can still have considerable policy importance when the baseline rate of the health outcome is high, and many persons are exposed. Assessing the certainty of the evidence based on these effect sizes is challenging because they can be prone to residual confounding due to the non-randomized nature of the evidence. When applying GRADE, a precise relative risk >2.0 increases the certainty in an existing effect because residual confounding is unlikely to explain the association. GRADE also suggests rating up when opposing plausible residual confounding exists for other effect sizes. In this concept paper, we propose using the E-value, defined as the smallest effect size of a confounder that still can reduce an observed RR to the null value, and a reference confounder to assess the likelihood of residual confounding. We propose a 4-step approach. 1. Assess the association of interest for relevant exposure levels. 2. Calculate the E-value for this observed association. 3. Choose a reference confounder with sufficient strength and information and assess its effect on the observed association using the E-value. 4. Assess how likely it is that residual confounding will still bias the observed RR. We present three case studies and discuss the feasibility of the approach.

To establish a body of evidence on safety for postmarketing Chinese medicine: A new research paradigm.

The issue of safety evaluation on postmarketing Chinese medicines has become a hot topic in mainland China recently. Researchers and decision-makers can obtain a variety of evidence resources about safety in order to evaluate the safety profile for postmarketing Chinese medicines. A registry study on ten Chinese medicine injections for postmarketing surveillance has come to the end. From such a study observing more than 300,000 patients for more than 4 years, a theoretical research question emerges, that is, how to identify and evaluate safety evidence systematically. We put forward a brand new research paradigm on the theory level, which is to establish a body of evidence on safety evaluation for postmarketing Chinese medicine. Therefore, multiple information sources were explored and extracted from preclinical experiments for toxicity, postmarketing clinical trials for effificacy and safety evaluation, registry study for surveillance, retrospective data analysis from hospital information system and spontaneous response system, and case reports and systematic review from literature. Greater efforts for this idea and cooperation with experts in this fifield both in China and abroad are urgently needed.

To establish a body of evidence on safety for postmarketing Chinese medicine: A new research paradigm / 中国结合医学杂志

The issue of safety evaluation on postmarketing Chinese medicines has become a hot topic in mainland China recently. Researchers and decision-makers can obtain a variety of evidence resources about safety in order to evaluate the safety profile for postmarketing Chinese medicines. A registry study on ten Chinese medicine injections for postmarketing surveillance has come to the end. From such a study observing more than 300,000 patients for more than 4 years, a theoretical research question emerges, that is, how to identify and evaluate safety evidence systematically. We put forward a brand new research paradigm on the theory level, which is to establish a body of evidence on safety evaluation for postmarketing Chinese medicine. Therefore, multiple information sources were explored and extracted from preclinical experiments for toxicity, postmarketing clinical trials for effificacy and safety evaluation, registry study for surveillance, retrospective data analysis from hospital information system and spontaneous response system, and case reports and systematic review from literature. Greater efforts for this idea and cooperation with experts in this fifield both in China and abroad are urgently needed.