Background: Two-sample Mendelian randomization (2SMR) is an increasingly popular epidemiological method that uses genetic variants as instruments for making causal inferences. Clear reporting of methods employed in such studies is important for evaluating their underlying quality. However, the quality of methodological reporting of 2SMR studies is currently unclear. Objectives: We aimed to assess the reporting quality of studies that used MR-Base, one of the most popular platforms for implementing 2SMR analysis. Methods: We searched Web of Science Core Collection, PsycInfo, MEDLINE, EMBASE and citations listed in Google Scholar of the MR-Base descriptor paper for any published MR study that used MR-Base during any component of the MR analysis. Studies were screened by two independent reviewers. We created a bespoke reporting checklist to evaluate reporting quality of 2SMR studies. Information was extracted by at least two independent reviewers. Results: 87 studies were included in the primary analysis, of which 14 had at least 10 phenotypes. Reporting quality was generally poor with a mean of 53% (SD = 14%) of items reported in each study. Many items required for evaluating the validity of key assumptions made in MR were poorly reported: only 44% of studies provided sufficient details for assessing if the variant associates with the exposure ('relevance' assumption), 31% for the assessing if there are any variant-outcome confounders ('independence' assumption), 89% for the assessing if the variant causes the outcome independently of the exposure ('exclusion restriction' assumption), and 32% for assumptions of falsification tests. We found no evidence of a change in reporting over time and findings were similar in a random sample of MR studies that did not use the MR-Base platform. Discussion: The quality of reporting of two-sample Mendelian randomization studies in our sample was generally poor. Journals and researchers should implement the STROBE-MR guidelines to improve reporting quality. Other: Funding: ESRC, Regression: This study pre-registered on the OSF, and the protocol can be found at DOI 10.17605/OSF.IO/NFM27

Undisclosed discrepancies often exist between study registrations and their associated publications. Discrepancies can increase risk of bias, and when undisclosed, they disguise this increased risk of bias from readers. To remedy this issue, we developed an intervention called discrepancy review. We provided journals with peer reviewers specifically assigned to check for undisclosed discrepancies between registrations and manuscripts submitted to journals. We performed discrepancy review on 18 manuscripts submitted to Nicotine and Tobacco Research and three manuscripts submitted to the European Journal of Personality. We iteratively refined the discrepancy review process based on feedback from discrepancy reviewers, editors and authors. Authors addressed the majority of discrepancy reviewer comments, and there was no opposition to running a trial from authors, editors or discrepancy reviewers. Outcome measures for a trial of discrepancy review could include the presence of primary or secondary outcome discrepancies, whether publications that are not the primary report from a clinical trial registration are clearly described as such, whether registrations are permanent, and an overarching subjective assessment of the impact of discrepancies in published articles. We found that discrepancy review could feasibly be introduced as a regular practice at some journals interested in this process. A full trial of discrepancy review would be needed to evaluate its impact on reducing undisclosed discrepancies.

Background: Registered Reports (RRs) could be a way to increase the quality of scientific research and literature, such as by reducing publication bias and increasing the rigour of study designs. These potential benefits have led to Registered Report funding partnerships (RRFPs or partnerships for short) between research funders and academic journals who collaborate to encourage researchers to publish RRs. In this study we investigated the research question: “What are the experiences of the stakeholders (authors, reviewers, journal editors, funders) in the various partnership models?”. Our companion paper addresses a related, but separate, research question. Methods: We conducted a thematic analysis of 32 semi-structured interviews with stakeholders (funders, editors, authors, reviewers, matchmakers) from six partnerships. Results: Interviewees had highly variable perceptions and experiences, reflecting the complex and nuanced impacts of partnerships. We identified 6 themes: “Importance of communication with authors and reviewers”, “Influence on study design”, “Appropriateness of partners”, “Potential to reduce publication bias”, “Impact on reviewer workload”, and “Insufficient evidence”. Conclusions: This was the first investigation into these novel initiatives. We hope that our findings can benefit and shape current and future partnerships.

Background: We studied a novel initiative – Registered Reports Funding Partnerships (RRFPs) – whereby research funders and journals partner in order to integrate their procedures for funding applications and Registered Reports submissions into one process. We investigated the feasibility of conducting a randomised controlled trial (RCT) of the impact of RRFPs on (1) research quality and (2) the efficiency of the research process, from funding to publication. Methods: We conducted 32 semi-structured interviews and follow-up questionnaires with stakeholders (funders, editors, authors, and reviewers) across six different RRFPs. Results: A RCT of RRFPs appears to be feasible in principle. The partnership concept seems worthwhile to pursue further and is adaptable to the needs of various funders and publishers, and across disciplines. Three primary outcomes of interest should be measurable, and participant randomisation could conceivably be done in a number of ways. In practice, however, the current volume of submissions going through existing partnerships is too low to support a full trial. Conclusions: Although a RCT of RRFPs is conceptually feasible, it will only be possible if organisations are willing to form new partnerships, scale up existing ones, and incorporate a trial (i.e., randomisation) into these partnerships.

Background: Registered Reports (RRs) could be a way to increase the quality of scientific research and literature, such as by reducing publication bias and increasing the rigour of study designs. These potential benefits have led to Registered Report funding partnerships (RRFPs or partnerships for short) between research funders and academic journals who collaborate to encourage researchers to publish RRs. In this study we investigated the research question: “What are the experiences of the stakeholders (authors, reviewers, journal editors, funders) in the various partnership models?”. Our companion paper addresses a related, but separate, research question. Methods: We conducted a thematic analysis of 32 semi-structured interviews with stakeholders (funders, editors, authors, reviewers, matchmakers) from six partnerships. Results: Interviewees had highly variable perceptions and experiences, reflecting the complex and nuanced impacts of partnerships. We identified 6 themes: “Importance of communication with authors and reviewers”, “Influence on study design”, “Appropriateness of partners”, “Potential to reduce publication bias”, “Impact on reviewer workload”, and “Insufficient evidence”. Conclusions: This was the first investigation into these novel initiatives. We hope that our findings can benefit and shape current and future partnerships.

Over the last two decades there has been growing concern that many published findings may not be robust. In recent years, a number of approaches have been suggested – such as pre-registration of study protocols, data and materials sharing – that may serve to improve research quality. This chapter discusses that factors that may contribute research quality, and the initiatives that may serve to encourage better research practices and improve research quality. To ensure these initiatives are effective we need more research on their positive impacts – as well as possible unintended consequences – on the accuracy and robustness of scientific findings.

Primary data collected during a research study is often shared and may be reused for new studies. To assess the extent of data sharing in favourable circumstances and whether data sharing checks can be automated, this article investigates summary statistics from primary human genome-wide association studies (GWAS). This type of data is highly suitable for sharing because it is a standard research output, is straightforward to use in future studies (e.g., for secondary analysis), and may be already stored in a standard format for internal sharing within multi-site research projects. Manual checks of 1799 articles from 2010 and 2017 matching a simple PubMed query for molecular epidemiology GWAS were used to identify 314 primary human GWAS papers. Of these, only 13% reported the location of a complete set of GWAS summary data, increasing from 3% in 2010 to 23% in 2017. Whilst information about whether data was shared was typically located clearly within a data availability statement, the exact nature of the shared data was usually unspecified. Thus, data sharing is the exception even in suitable research fields with relatively strong data sharing norms. Moreover, the lack of clear data descriptions within data sharing statements greatly complicates the task of automatically characterising shared data sets.

Genome-wide association studies have identified associations between variation at rs16969968/rs1051730 in the CHRNA5–A3–B4 gene cluster and smoking related outcomes. Experiments in rodents have described the nicotinic acetylcholine receptors (nAChRs) subunits encoded by this gene cluster and showed a lack of nicotine aversion in nAChRs deficient animal models. We conducted a nicotine challenge and a smoking topography study in humans, hypothesising that: 1. responses to a nicotine challenge would differ according to the rs16969968/rs1051730 genotype and 2. genotype may influence nicotine intake via smoking topography.We used linear regressions to examine associations between rs16969968/rs1051730 genotype and subjective (questionnaires) and objective (physiological parameters) responses following acute nicotine exposure in never smokers (hypothesis 1) or cigarette smoking in current smokers (hypothesis 2). There was evidence to suggest nicotine exposure increases blood pressure and heart rate, and negatively affects mood, but insufficient evidence that these effects differ by genotype. Carriers of the minor allele following smoking one cigarette, exhibited reduced cravings (b=-2.46, 95% CI -4.87 to - 0.06, p=0.04) and inhaled less smoke per cigarette (b=-0.24, 95% CI - 0.43 to - 0.06, p=0.01) and per puff (b=-0.18, 95% CI -0.32 to -0.01, p=0.02). These results suggest that we need to carefully consider the translational value of the findings of aversion behaviour in nAChRs rodent models, and that deeper inhalation does not explain the strong association between rs16969968/rs1051730 genotype and objective biomarkers of tobacco exposure.

BACKGROUND:Alcohol labeling provides a relatively low-cost, population-level approach to providing information about alcohol's content and harms. METHOD:We conducted an online between-subjects experiment with two tasks to examine the impact of alcohol labels (n = 1884). In one task, participants were randomized to view one of four different unit labels (including labels currently used by the alcohol industry and novel labels which provide more information about how the number of units relates to recommended drinking guidelines). We assessed participants' accuracy of estimating weekly serving limits of alcohol. In a second task, participants were randomized to view one of eight health warnings (which varied according to message content, specificity, and framing). We assessed the motivation to quit after viewing the health warning. RESULTS:Accuracy of estimating weekly serving limits of alcohol was greater for participants who viewed novel unit labels compared to the industry standard labels. Motivation to drink less was higher amongst participants who had viewed both cancer and negatively framed messages, compared to mental health and positively framed messages. CONCLUSION:Existing unit labels used by the alcohol industry can be improved; the inclusion of unit information per serving and how these relate to low-risk drinking guidelines may be important for facilitating consumer understanding. Health warning labels should be included alongside units to provide consumers with information about the harms associated with alcohol and discourage riskier drinking behavior.