المؤلفون: Gryaznov, D, von Niederhäusern, B, Speich, B, Kasenda, B, Ojeda-Ruiz, E, Blümle, A, Schandelmaier, S, Mertz, D, Odutayo, A, Tomonaga, Y, Amstutz, A, Pauli-Magnus, C, Gloy, V, Lohner, S, Bischoff, K, Wollmann, K, Rehner, L, Meerpohl, JJ, Nordmann, A, Klatte, K, Ghosh, N, Taji Heravi, A, Wong, J, Chow, N, Hong, P, McCord-De Iaco, KA, Sricharoenchai, S, Busse, JW, Agarwal, A, Saccilotto, R, Schwenkglenks, M, Moffa, G, Hemkens, L, Hopewell, S, Von Elm, E, Briel, M

الوصف: Objectives Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist. Design Repeated cross sectional study. Setting Swiss, German and Canadian research ethics committees (RECs). Participants RCT protocols approved by RECs in 2012 (n=257) and 2016 (n=292). Primary and secondary outcome measures The primary outcomes were the proportion of reported SPIRIT items per protocol and the proportion of trial protocols reporting individual SPIRIT items. We compared these outcomes in protocols approved in 2012 and 2016, and built regression models to explore factors associated with adherence to SPIRIT. For each protocol, we also extracted information on general trial characteristics and assessed whether individual SPIRIT items were reported. Results The median proportion of reported SPIRIT items among RCT protocols showed a non-significant increase from 72% (IQR, 63%–79%) in 2012 to 77% (IQR, 68%–82%) in 2016. However, in a preplanned subgroup analysis, we detected a significant improvement in investigator-sponsored protocols: the median proportion increased from 64% (IQR, 55%–72%) in 2012 to 76% (IQR, 64%–83%) in 2016, while for industry-sponsored protocols median adherence was 77% (IQR 72%–80%) for both years. The following trial characteristics were independently associated with lower adherence to SPIRIT: single-centre trial, no support from a clinical trials unit or contract research organisation, and investigator-sponsorship. Conclusions In 2012, industry-sponsored RCT protocols were reported more comprehensively than investigator-sponsored protocols. After publication of the SPIRIT checklist, investigator-sponsored protocols improved to the level of ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:056e96eb-fcd6-47a5-80b0-b5413b7dfb41Test; https://doi.org/10.1136/bmjopen-2021-053417Test

الإتاحة: https://doi.org/10.1136/bmjopen-2021-053417Test
https://ora.ox.ac.uk/objects/uuid:056e96eb-fcd6-47a5-80b0-b5413b7dfb41Test

المؤلفون: Speich, B, Gryaznov, D, Busse, JW, Gloy, VL, Lohner, S, Klatte, K, Taji Heravi, A, Ghosh, N, Lee, H, Mansouri, A, Marian, IR, Saccilotto, R, Nury, E, Kasenda, B, Ojeda-Ruiz, E, Schandelmaier, S, Tomonaga, Y, Amstutz, A, Pauli-Magnus, C, Bischoff, K, Wollmann, K, Rehner, L, Meerpohl, JJ, Nordmann, A, Wong, J, Chow, N, Hong, PJ, Mc Cord-De Iaco, K, Sricharoenchai, S, Agarwal, A, Schwenkglenks, M, Hemkens, LG, von Elm, E, Copsey, B, Griessbach, AN, Schönenberger, C, Mertz, D, Blümle, A, von Niederhäusern, B, Hopewell, S, Odutayo, A, Briel, M

الوصف: Background We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. Methods and findings We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:296e27c0-9a6b-45fa-9f58-1b8c7ab97b8bTest; https://doi.org/10.1371/journal.pmed.1003980Test

الإتاحة: https://doi.org/10.1371/journal.pmed.1003980Test
https://ora.ox.ac.uk/objects/uuid:296e27c0-9a6b-45fa-9f58-1b8c7ab97b8bTest

المؤلفون: Lohner, S, Gryaznov, D, von Niederhäusern, B, Speich, B, Kasenda, B, Ojeda-Ruiz, E, Schandelmaier, S, Mertz, D, Odutayo, A, Tomonaga, Y, Amstutz, A, Pauli-Magnus, C, Gloy, V, Bischoff, K, Wollmann, K, Rehner, L, Meerpohl, JJ, Nordmann, A, Klatte, K, Ghosh, N, Heravi, AT, Wong, J, Chow, N, Hong, PJ, Cord, KM, Sricharoenchai, S, Busse, JW, Agarwal, A, Saccilotto, R, Schwenkglenks, M, Moffa, G, Hemkens, LG, Hopewell, S, von Elm, E, Blümle, A, Briel, M

الوصف: Objectives To investigate the adherence of randomised controlled trial (RCT) protocols evaluating non-regulated interventions (including dietary interventions, surgical procedures, behavioural and lifestyle interventions, and exercise programmes) in comparison with regulated interventions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement. Methods We conducted a repeated cross-sectional investigation in a random sample of RCT protocols approved in 2012 (n = 257) or 2016 (n = 292) by research ethics committees in Switzerland, Germany, or Canada. We investigated the proportion of accurately reported SPIRIT checklist items in protocols of trials with non-regulated as compared to regulated interventions. Results Overall, 131 (24%) of trial protocols tested non-regulated interventions. In 2012, the median proportion of SPIRIT items reported in these protocols (59%, interquartile range [IQR], 53%-69%) was lower than in protocols with regulated interventions (median, 74%, IQR, 66%-80%). In 2016, the reporting quality of protocols with non-regulated interventions (median, 75%, IQR, 62%-83%) improved to the level of regulated intervention protocols, which had not changed on average. Conclusions Reporting of RCT protocols evaluating non-regulated interventions improved between 2012 and 2016, although remained suboptimal. SPIRIT recommendations need to be further endorsed by researchers, ethics committees, funding agencies, and journals to optimize reporting of RCT protocols.

العلاقة: https://ora.ox.ac.uk/objects/uuid:50c907c7-95ca-4f54-91e0-19c9383088c6Test; https://doi.org/10.1016/j.jclinepi.2021.05.011Test

الإتاحة: https://doi.org/10.1016/j.jclinepi.2021.05.011Test
https://ora.ox.ac.uk/objects/uuid:50c907c7-95ca-4f54-91e0-19c9383088c6Test

المؤلفون: Gryaznov, D, Odutayo, A, von Niederhäusern, B, Speich, B, Kasenda, B, Ojeda-Ruiz, E, Blümle, A, Schandelmaier, S, Mertz, D, Tomonaga, Y, Amstutz, A, Pauli-Magnus, C, Gloy, V, Bischoff, K, Wollmann, K, Rehner, L, Lohner, S, Meerpohl, JJ, Nordmann, A, Klatte, K, Ghosh, N, Heravi, AT, Wong, J, Chow, N, Hong, PJ, Cord, KM, Sricharoenchai, S, Busse, JW, Agarwal, A, Saccilotto, R, Schwenkglenks, M, Moffa, G, Hemkens, LG, Hopewell, S, von Elm, E, Briel, M

الوصف: Background: Clearly structured and comprehensive protocols are an essential component to ensure safety of participants, data validity, successful conduct, and credibility of results of randomized clinical trials (RCTs). Funding agencies, research ethics committees (RECs), regulatory agencies, medical journals, systematic reviewers, and other stakeholders rely on protocols to appraise the conduct and reporting of RCTs. In response to evidence of poor protocol quality, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline was published in 2013 to improve the accuracy and completeness of clinical trial protocols. The impact of these recommendations on protocol completeness and associations between protocol completeness and successful RCT conduct and publication remain uncertain. Objectives and Methods: Aims of the Adherence to SPIrit REcommendations (ASPIRE) study are to investigate adherence to SPIRIT checklist items of RCT protocols approved by RECs in the UK, Switzerland, Germany, and Canada before (2012) and after (2016) the publication of the SPIRIT guidelines; determine protocol features associated with non-adherence to SPIRIT checklist items; and assess potential differences in adherence across countries. We assembled an international cohort of RCTs based on 450 protocols approved in 2012 and 402 protocols approved in 2016 by RECs in Switzerland, the UK, Germany, and Canada. We will extract data on RCT characteristics and adherence to SPIRIT for all included protocols. We will use multivariable regression models to investigate temporal changes in SPIRIT adherence, differences across countries, and associations between SPIRIT adherence of protocols with RCT registration, completion, and publication of results. We plan substudies to examine the registration, premature discontinuation, and non-publication of RCTs; the use of patient-reported outcomes in RCT protocols; SPIRIT adherence of RCT protocols with non-regulated interventions; the planning of RCT subgroup analyses; ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:4d517411-eba7-4950-868c-9767f9322e75Test; https://doi.org/10.1186/s13063-020-04808-yTest

الإتاحة: https://doi.org/10.1186/s13063-020-04808-yTest
https://ora.ox.ac.uk/objects/uuid:4d517411-eba7-4950-868c-9767f9322e75Test

المؤلفون: González-González, AI, Dinh, TS, Meid, AD, Blom, JW, van den Akker, M, Elders, PJM, Thiem, U, Kuellenberg de Gaudry, D, Snell, KIE, Perera, R, Swart, KMA, Rudolf, H, Bosch-Lenders, D, Trampisch, H-J, Meerpohl, JJ, Flaig, B, Kom, G, Gerlach, FM, Hafaeli, WE, Glasziou, PP, Muth, C

الوصف: The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/time-intensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process.

العلاقة: https://ora.ox.ac.uk/objects/uuid:c5c16131-8e7f-461d-a586-5c9b44ca5dd0Test; https://doi.org/10.1016/j.mad.2021.111436Test

الإتاحة: https://doi.org/10.1016/j.mad.2021.111436Test
https://ora.ox.ac.uk/objects/uuid:c5c16131-8e7f-461d-a586-5c9b44ca5dd0Test

المؤلفون: González-González, AI, Meid, AD, Dinh, TS, Blom, JW, van den Akker, M, Elders, PJM, Thiem, U, De Gaudry, DK, Swart, KMA, Rudolf, H, Bosch-Lenders, D, Trampisch, H-J, Meerpohl, JJ, Gerlach, FM, Flaig, B, Kom, G, Snell, KIE, Perera, R, Haefeli, WE, Glasziou, PP, Muth, C

الوصف: Objectives: To develop and validate a prognostic model to predict deterioration in health-related quality of life (dHRQoL) in older general practice patients with at least one chronic condition and one chronic prescription. Study Design and Setting: We used individual participant data from five cluster-randomized trials conducted in the Netherlands and Germany to predict dHRQoL, defined as a decrease in EQ-5D-3 L index score of ≥5% after 6-month follow-up in logistic regression models with stratified intercepts to account for between-study heterogeneity. The model was validated internally and by using internal–external cross-validation (IECV). Results: In 3,582 patients with complete data, of whom 1,046 (29.2%) showed deterioration in HRQoL, and 12/87 variables were selected that were related to single (chronic) conditions, inappropriate medication, medication underuse, functional status, well-being, and HRQoL. Bootstrap internal validation showed a C-statistic of 0.71 (0.69 to 0.72) and a calibration slope of 0.88 (0.78 to 0.98). In the IECV loop, the model provided a pooled C-statistic of 0.68 (0.65 to 0.70) and calibration-in-the-large of 0 (−0.13 to 0.13). HRQoL/functionality had the strongest prognostic value. Conclusion: The model performed well in terms of discrimination, calibration, and generalizability and might help clinicians identify older patients at high risk of dHRQoL.

العلاقة: https://ora.ox.ac.uk/objects/uuid:fe2cfc90-df28-46cb-b19f-89d3effc0e62Test; https://doi.org/10.1016/j.jclinepi.2020.10.006Test

الإتاحة: https://doi.org/10.1016/j.jclinepi.2020.10.006Test
https://ora.ox.ac.uk/objects/uuid:fe2cfc90-df28-46cb-b19f-89d3effc0e62Test