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INTRODUCTION: Blinding is a methodologically important aspect in randomised controlled trials yet frequently overlooked in trials of spinal manual therapy interventions for back pain. To help inform the blinding methods of a future, double-placebo-controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain, we set four objectives: (1) to assess the feasibility of blinding participants, randomly allocated to an active or placebo-control spinal manual therapy intervention protocol, (2) to assess the feasibility of blinding outcome assessors within the trial, (3) to explore the influence of spinal manual therapy experience and low back pain on blinding, and (4) to explore factors contributing to perceptions about intervention assignment among participants and outcome assessors. METHODS AND ANALYSIS: Two-parallel-group, single-centre, placebo-controlled, methodological blinding feasibility randomised trial. We will recruit between 60 and 100 adults with or without back pain and with or without experience of spinal manual therapy from Zurich, Switzerland. Participants will be randomised to either an active spinal manual therapy or a placebo-control spinal manual therapy protocol-both interventions delivered over two study visits, up to two weeks apart. The primary outcome is participant blinding using the Bang blinding index within each intervention arm immediately after each of the two study visits. Secondary outcomes are participant blinding using the James blinding index, outcome assessor blinding (Bang and James blinding indices), self-reported factors influencing perceived intervention assignment among participants and outcome assessors, and participant-reported credibility and expectancy of study interventions. Other outcomes-included to blind the study objective from participants-are lumbar spine range of motion, self-rated general health, satisfaction with care, pain intensity, and function. Intervention provider outcomes include intervention component fidelity and quality of intervention delivery. ETHICS AND DISSEMINATION: The independent ethics commission of Canton Zurich granted ethical approval for this study (KEK 2023-00381). Written informed consent will be obtained from all participants. Findings will be disseminated in scientific conferences and a peer-reviewed publication and inform the blinding methods of a future double-placebo controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain-the SALuBRITY trial. TRIAL REGISTRATION: NCT05778396.

Abstract Background A Bayesian approach may be useful in the study of possible treatment-related rare serious adverse events, particularly when there are strongly held opinions in the absence of good quality previous data. We demonstrate the application of a Bayesian analysis by integrating expert opinions with population-based epidemiologic data to investigate the association between chiropractic care and acute lumbar disc herniation (LDH) with early surgery. Methods Experts’ opinions were used to derive probability distributions of the incidence rate ratio (IRR) for acute LDH requiring early surgery associated with chiropractic care. A ‘community of priors’ (enthusiastic, neutral, and skeptical) was built by dividing the experts into three groups according to their perceived mean prior IRR. The likelihood was formed from the results of a population-based epidemiologic study comparing the relative incidence of acute LDH with early surgery after chiropractic care versus primary medical care, with sensitive and specific outcome case definitions and surgery occurring within 8- and 12-week time windows after acute LDH. The robustness of results to the community of priors and specific versus sensitive case definitions was assessed. Results The most enthusiastic 25% of experts had a prior IRR of 0.42 (95% credible interval [CrI], 0.03 to 1.27), while the most skeptical 25% of experts had a prior IRR of 1.66 (95% CrI, 0.55 to 4.25). The Bayesian posterior estimates across priors and outcome definitions ranged from an IRR of 0.39 (95% CrI, 0.21 to 0.68) to an IRR of 1.40 (95% CrI, 0.52 to 2.55). With a sensitive definition of the outcome, the analysis produced results that confirmed prior enthusiasts’ beliefs and that were precise enough to shift prior beliefs of skeptics. With a specific definition of the outcome, the results were not strong enough to overcome prior skepticism. Conclusion A Bayesian analysis integrating expert beliefs highlighted the value of eliciting informative priors to better understand how new evidence ought to update prior existing beliefs. Clinical epidemiologists are encouraged to integrate informative and expert opinions representing the end-user community of priors in Bayesian analyses, particularly when there are strongly held opinions in the absence of definitive scientific evidence.

Abstract Introduction Blinding is a methodologically important aspect in randomised controlled trials yet frequently overlooked in trials of spinal manual therapy interventions for back pain. To help inform the blinding methods of a future, double-placebo-controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain, we set four objectives: (1) to assess the feasibility of blinding participants, randomly allocated to an active or placebo-control spinal manual therapy intervention protocol, (2) to assess the feasibility of blinding outcome assessors within the trial, (3) to explore the influence of spinal manual therapy experience and low back pain on blinding, and (4) to explore factors contributing to perceptions about intervention assignment among participants and outcome assessors. Methods and analysis Two-parallel-group, single-centre, placebo-controlled, methodological blinding feasibility randomised trial. We will recruit between 60 and 100 adults with or without back pain and with or without experience of spinal manual therapy from Zurich, Switzerland. Participants will be randomised to either an active spinal manual therapy or a placebo-control spinal manual therapy protocol—both interventions delivered over two study visits, up to two weeks apart. The primary outcome is participant blinding using the Bang blinding index within each intervention arm immediately after each of the two study visits. Secondary outcomes are participant blinding using the James blinding index, outcome assessor blinding (Bang and James blinding indices), self-reported factors influencing perceived intervention assignment among participants and outcome assessors, and participant-reported credibility and expectancy of study interventions. Other outcomes—included to blind the study objective from participants—are lumbar spine range of motion, self-rated general health, satisfaction with care, pain intensity, and function. Intervention provider outcomes include intervention component fidelity and quality of intervention delivery. Ethics and dissemination The independent ethics commission of Canton Zurich granted ethical approval for this study (KEK 2023–00381). Written informed consent will be obtained from all participants. Findings will be disseminated in scientific conferences and a peer-reviewed publication and inform the blinding methods of a future double-placebo controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain—the SALuBRITY trial. Trial registration NCT05778396.

Abstract Study design Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. Background Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. Methods On 7–8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from –1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating ‘random guessing’—balanced ‘active’ and ‘control’ perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. Results 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, −0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (−0.12 to 0.30) and −0.10 (−0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment. Conclusions Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed. Trial registration ClinicalTrials.gov: NCT05822947 (retrospectively registered)

Abstract Background Spinal manual therapy and corticosteroid nerve root injection are commonly used to treat patients with lumbar radiculopathy. The SALuBRITY trial—a two parallel group, double sham controlled, randomised clinical trial—is being developed to compare their effectiveness. By gathering patients’ and clinicians’ perspectives and involving them in discussions related to the trial research question and objectives, proposed trial recruitment processes, methods, and outcome measures, we aimed to improve the relevance and quality of the SALuBRITY trial. Methods We involved patients with lived experience of lumbar radiculopathy (n = 5) and primary care clinicians (n = 4) with experience in the treatment of these patients. Involvement activities included an initial kick-off event to introduce the project, establishing a shared purpose statement, and empowering patient and clinician advisors for their involvement, followed by semi-structured group and individual interviews, and questionnaires to evaluate the experience throughout the project. Results Both patient and clinician advisors endorsed the significance and relevance of the trial’s objectives. Patients assessed the proposed trial methods as acceptable within the context of a trusting patient-clinician relationship. A trial recruitment and enrolment target time of up to five days was regarded as acceptable, although patients with chronic radiculopathy may need more time to consider their trial participation decision. All advisors reached consensus on the acceptability of a medication washout phase of 12- to 24-h before pain outcome measurement, with the inclusion of a rescue medication protocol. Both advisory groups preferred leg pain over back pain as the primary clinical outcome, with patient advisors advocating for personalized primary pain localization. Furthermore, patients requested expanding the pain, enjoyment, and general activity scale with peak pain intensity, rather than average pain alone. Patient and clinician advisors evaluated their engagement in clinical research as meaningful and impactful. Conclusion Patient and public involvement resulted in important and relevant considerations for the SALuBRITY trial, spanning all research phases. These findings hold promise for enhancing the trial’s quality and relevance and improving its translation into clinical practice.

Abstract Background Evidence-based practice (EBP) is the integration of best research evidence with clinical expertise and patients’ values and preferences. Little is known about knowledge, attitudes, and application of EBP among chiropractic students and trainees. Our aims were to (1) examine the feasibility of implementing a new journal club format within a Swiss university chiropractic healthcare education setting, and (2) assess the associations between the new journal club implementation and EBP characteristics among chiropractic students. Methods A before-and-after study was conducted through a newly implemented journal club with 5th and 6th year chiropractic students and postgraduate trainees between 1 February 2021 and 31 July 2021. The journal club was developed based on the “community of practice” and “team-based learning” conceptual frameworks. EBP knowledge, attitudes, personal application, and future use, were assessed with a validated questionnaire. We summarised participant characteristics using descriptive statistics, estimated before-and-after EBP total and subscale scores (i.e., knowledge, attitudes, personal application, and future use), and conducted an exploratory subgroup analysis based on journal club attendance (Group A: 3–5 sessions attended; Group B: ≤ 2 sessions attended). Results Among 32 eligible students and trainees, 29 participants (mean age 26 years; 79% women) were enrolled: 25 (78%) responded to the pre- and 29 (91%) to the post-assessment surveys. Most (80%) were chiropractic students and 20% were postgraduate trainees. Group A consisted of 12 (41%) and Group B of 17 (59%) participants, respectively. We found reasonable feasibility for the new journal club format and our findings were compatible with no difference in before-and-after EBP scores (median EBP total score before: 72.6 [IQR, 63.7–77.4], and after: 73.4 [IQR, 61.3–78.2]). Exploratory subgroup analyses based on journal club attendance were consistent with our overall findings. Conclusion Our study suggests that the newly implemented journal club and embedding chiropractic educational research within the journal club were feasible and acceptable. Small before-and-after differences in the EBP subscale scores for knowledge, attitudes, personal application, and future use were observed in chiropractic students and postgraduate trainees. The small study size and short timeframe during a single semester limit potential inferences.

Abstract Background The implementation of electronic health information technologies is a key target for healthcare quality improvement. Among Swiss chiropractors, reliable data on the use of electronic heath information technologies and distribution of the health workforce was lacking. Objectives To estimate the prevalence of electronic patient record (EPR) and encrypted email communication use among Swiss chiropractors and describe the geographic distribution of chiropractors in Switzerland. Methods Population-based cross-sectional study of all active practising members of the Swiss Chiropractic Association (ChiroSuisse) between 3 December 2019 and 31 January 2020. We asked about clinician and practice characteristics, EPR use for clinical record keeping, use of encrypted email for patient communication, and information on EPR and encrypted email communication products used. Multivariable logistic regression analyses assessed the associations between clinician and practice characteristics and (1) EPR use, and (2) encrypted email use. Results Among 286 eligible Swiss chiropractors (193 [68%] men; mean age, 51.4 [SD, 11.2] years), 217 (76%) completed the survey (140 [65%] men; mean age 50.7 [11.2] years). Among respondents, 47% (95% confidence interval [CI], 40–54%) reported using an EPR in their practice, while 60% (95% CI, 54–67%) endorsed using encrypted email technology. Chiropractors aged ≥ 60 (versus those ≤ 39) years were 74% less likely to use an EPR system (OR 0.26, 95% CI 0.08 to 0.77), while clinicians from practices with 4 or more chiropractors (versus those from solo practices) were over 5 times more likely to report EPR use (OR 5.6, 2.1 to 16.5). Findings for factors associated with encrypted email use were similar. The density of chiropractors in Switzerland was 3.3 per 100,000 inhabitants. Conclusions As of January 2020, 286 duly licensed chiropractors were available to provide musculoskeletal healthcare in Switzerland — just under 50% of responding Swiss chiropractors used an EPR system in clinical practice, while 60% used encrypted email technology. Better implementation of EPR and electronic health information technologies in Swiss chiropractic practice is possible and encouraged for the purpose of musculoskeletal healthcare quality improvement.

Abstract The Swiss chiropractic practice-based research network (PBRN) is a nationwide project developed in collaboration with patients, clinicians, and academic stakeholders to advance musculoskeletal epidemiologic research. The aim of this study was to describe the clinician population recruited and representativeness of this PBRN to inform future collaboration. A population-based cross-sectional study was performed. PBRN clinician characteristics were described and factors related to motivation (operationalised as VAS score ≥ 70) to participate in a subsequent patient cohort pilot study were assessed. Among 326 eligible chiropractors, 152 enrolled in the PBRN (47% participation). The PBRN was representative of the larger Swiss chiropractic population with regards to age, language, and geographic distribution. Of those enrolled, 39% were motivated to participate in a nested patient cohort pilot study. Motivation was associated with age 40 years or older versus 39 years or younger (OR 2.3, 95% CI 1.0–5.2), and with a moderate clinic size (OR 2.4, 95% CI 1.1–5.7) or large clinic size (OR 2.8, 95% CI 1.0–7.8) versus solo practice. The Swiss chiropractic PBRN has enrolled almost half of all Swiss chiropractors and has potential to facilitate collaborative practice-based research to improve musculoskeletal health care quality. Trial registration: Swiss chiropractic PBRN (ClinicalTrials.gov identifier: NCT05046249); Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020).

Objectives: To describe and assess the risk of bias of the primary input studies that underpinned the Global Burden of Disease Study (GBD) 2019 modelled prevalence estimates of low back pain (LBP), neck pain (NP), and knee osteoarthritis (OA), from Australia, Brazil, Canada, Spain, and Switzerland. To evaluate the certainty of the GBD modelled prevalence evidence.Methods: Primary studies were identified using the GBD Data Input Sources Tool and their risk of bias was assessed using a validated tool. We rated the certainty of modelled prevalence estimates based on the GRADE Guidelines 30―the GRADE approach for modelled evidence.Results: Seventy-two primary studies (LBP: 67, NP: 2, knee OA: 3) underpinned the GBD estimates. Most studies had limited representativeness of their study populations, used suboptimal case definitions and applied assessment instruments with unknown psychometric properties. The certainty of modelled prevalence estimates was low, mainly due to risk of bias and indirectness.Conclusion: Beyond the risk of bias of primary input studies for LBP, NP, and knee OA in GBD 2019, the certainty of country-specific modelled prevalence estimates still have room for improvement.

Abstract Background The Balgrist University Hospital in Zurich, Switzerland, is an academic hospital focused on musculoskeletal disorders. An integrated chiropractic medicine clinic provides chiropractic care to a broad patient population. This health services research study aims to advance understanding of chiropractic healthcare service for quality assurance and healthcare quality improvement. Methods We performed an observational clinical cohort study at the Balgrist chiropractic medicine outpatient clinic in 2019. The records of all patients with initial visits or returning initial visits (> 3 months since last visit) and their subsequent visits from January 1, 2019, to December 31, 2019, were used to create the study dataset. Data collected included demographic characteristics, diagnoses, imaging data, conservative treatments, surgeries, and other clinical care data. Descriptive statistics were used to summarize data. Results 1844 distinct patients (52% female, mean age 48 ± 17 years) were eligible and included in the study. 1742 patients had a single initial visit, 101 had 2 initial visits, and 1 patient had 3 initial visits during the study period (total of 1947 initial visit records). The most common main diagnoses were low back pain (42%; 95% CI 40–46%), neck pain (22%; 20–24%), and thoracic pain (8%; 7–9%). 32% of patients presented with acute ( 12 weeks). Patients had a median of 5 chiropractic visits during their episode of care within a median of 28 days duration. Only 49% (95% CI 47–52%) of patient records had a clinical outcome that was extractable from routine clinical documentation in the hospital information system. Conclusion This health services study provides an initial understanding of patient characteristics and healthcare delivered in a Swiss academic hospital chiropractic outpatient setting and areas for improved clinical data quality assurance. A more concerted effort to systematically collect patient reported outcome measures would be a worthwhile healthcare quality improvement initiative.

Introduction Musculoskeletal (MSK) pain conditions, a leading cause of global disability, are usually first managed in primary care settings such as medical, physiotherapy, and chiropractic community-based practices. While chiropractors often treat MSK conditions, there is limited real-world evidence on the topic of health service outcomes among patients receiving this type of care. A nationwide Swiss chiropractic practice-based research network (PBRN) and MSK pain patient cohort study will have potential to monitor the epidemiological trends of MSK pain conditions and contribute to healthcare quality improvement. The primary aims of this protocol are to (1) describe the development of an MSK-focused PBRN within the Swiss chiropractic setting, and (2) describe the methodology of the first nested study to be conducted within the PBRN—an observational prospective patient cohort pilot study.Methods and analysis This initiative is conceptualised with two distinct phases. Phase I focuses on the development of the Swiss chiropractic PBRN, and will use a cross-sectional design to collect information from chiropractic clinicians nationwide. Phase II will recruit consecutive patients aged 18 years or older with MSK pain from community-based chiropractic practices participating in the PBRN into a prospective chiropractic cohort pilot study. All data collection will occur through electronic surveys offered in the three Swiss official languages (German, French, Italian) and English. Surveys will be provided to patients prior to their initial consultation in clinics, 1 hour after initial consultation, and at 2, 6 and 12 weeks after initial consultation.Ethics and dissemination Ethics approval has been obtained from the independent research ethics committee of Canton Zurich (BASEC-Nr: 2021-01479). Informed consent will be obtained electronically from all participants. Findings will be reported to stakeholders after each study phase, presented at local and international conferences, and disseminated through peer-reviewed publications.Study pre-registration Phase I—Swiss chiropractic PBRN (ClinicalTrials.gov identifier: NCT05046249); Phase 2—Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020).

Abstract Background Due to clinical and methodological diversity, clinical studies included in meta-analyses often differ in ways that lead to differences in treatment effects across studies. Meta-regression analysis is generally recommended to explore associations between study-level characteristics and treatment effect, however, three key pitfalls of meta-regression may lead to invalid conclusions. Our aims were to determine the frequency of these three pitfalls of meta-regression analyses, examine characteristics associated with the occurrence of these pitfalls, and explore changes between 2002 and 2012. Methods A meta-epidemiological study of studies including aggregate data meta-regression analysis in the years 2002 and 2012. We assessed the prevalence of meta-regression analyses with at least 1 of 3 pitfalls: ecological fallacy, overfitting, and inappropriate methods to regress treatment effects against the risk of the analysed outcome. We used logistic regression to investigate study characteristics associated with pitfalls and examined differences between 2002 and 2012. Results Our search yielded 580 studies with meta-analyses, of which 81 included meta-regression analyses with aggregated data. 57 meta-regression analyses were found to contain at least one pitfall (70%): 53 were susceptible to ecological fallacy (65%), 14 had a risk of overfitting (17%), and 5 inappropriately regressed treatment effects against the risk of the analysed outcome (6%). We found no difference in the prevalence of meta-regression analyses with methodological pitfalls between 2002 and 2012, nor any study-level characteristic that was clearly associated with the occurrence of any of the pitfalls. Conclusion The majority of meta-regression analyses based on aggregate data contain methodological pitfalls that may result in misleading findings.

Abstract Background A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial. Objectives We convened a Global Summit of international scientists to conduct a systematic review of the literature to determine the efficacy and effectiveness of SMT for the primary, secondary and tertiary prevention of non-musculoskeletal disorders. Global summit The Global Summit took place on September 14–15, 2019 in Toronto, Canada. It was attended by 50 researchers from 8 countries and 28 observers from 18 chiropractic organizations. At the summit, participants critically appraised the literature and synthesized the evidence. Systematic review of the literature We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health, and the Index to Chiropractic Literature from inception to May 15, 2019 using subject headings specific to each database and free text words relevant to manipulation/manual therapy, effectiveness, prevention, treatment, and non-musculoskeletal disorders. Eligible for review were randomized controlled trials published in English. The methodological quality of eligible studies was assessed independently by reviewers using the Scottish Intercollegiate Guidelines Network (SIGN) criteria for randomized controlled trials. We synthesized the evidence from articles with high or acceptable methodological quality according to the Synthesis without Meta-Analysis (SWiM) Guideline. The final risk of bias and evidence tables were reviewed by researchers who attended the Global Summit and 75% (38/50) had to approve the content to reach consensus. Results We retrieved 4997 citations, removed 1123 duplicates and screened 3874 citations. Of those, the eligibility of 32 articles was evaluated at the Global Summit and 16 articles were included in our systematic review. Our synthesis included six randomized controlled trials with acceptable or high methodological quality (reported in seven articles). These trials investigated the efficacy or effectiveness of SMT for the management of infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. None of the trials evaluated the effectiveness of SMT in preventing the occurrence of non-musculoskeletal disorders. Consensus was reached on the content of all risk of bias and evidence tables. All randomized controlled trials with high or acceptable quality found that SMT was not superior to sham interventions for the treatment of these non-musculoskeletal disorders. Six of 50 participants (12%) in the Global Summit did not approve the final report. Conclusion Our systematic review included six randomized clinical trials (534 participants) of acceptable or high quality investigating the efficacy or effectiveness of SMT for the treatment of non-musculoskeletal disorders. We found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function. Governments, payers, regulators, educators, and clinicians should consider this evidence when developing policies about the use and reimbursement of SMT for non-musculoskeletal disorders.

Introduction A patient and public involvement (PPI) project will be embedded within the SALuBRITY pilot trial, a two parallel group, double sham controlled, randomised clinical trial. The study aims to compare the effectiveness of spinal manual therapy and corticosteroid nerve root injections, two methods commonly used to treat patients with lumbar radiculopathy. We aim to gather patients’ and clinicians’ perspectives and involve them in decisions related to the research question and objectives, proposed trial recruitment processes and methods, and proposed outcome measures.Methods and analysis A small group of patients with lived experience of lumbar radiculopathy and primary care clinicians with experience in the treatment of patients with lumbar radiculopathy are involved. An initial kickoff event will prepare and empower the advisors for involvement in the project, followed by semistructured patient group and one-on-one clinician interviews. We will follow the Critical Outcomes of Research Engagement framework for assessing the impact of patient engagement in research. We will summarise and feedback PPI content to the patient and clinician advisors during a member-checking process to ensure accurate interpretation of patient and clinician inputs. Inductive and deductive thematic analysis will be used for the qualitative analysis of the interviews. Two surveys will be completed at different points along the trial to track the advisors’ and researchers’ experiences over the course of the PPI project. Any modifications to the SALuBRITY trial methods due to PPI inputs will be thoroughly documented and recorded in an impact log.Ethics and dissemination The independent research ethics committee of Canton Zurich confirmed that ethical approval for this PPI subproject was not required. PPI results will be disseminated in a peer-reviewed journal and presented at conferences.

Background This study aimed to assess the effectiveness of sodium‐glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes. Methods and Results We conducted a Bayesian meta‐analysis of randomized controlled trials comparing sodium‐glucose cotransporter 2 inhibitors with placebo. We used meta‐regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty‐three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63–0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69–1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72–1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61–1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63–1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71–1.08), with a 90.1% to 98.7% probability for the true RR to be