Retrieval of individual patient data depended on study characteristics : a randomized controlled trial

OBJECTIVE: To examine the effect of providing a financial incentive to authors of randomized clinical trials (RCTs) to obtain individual patient data (IPD). STUDY DESIGN AND SETTING: Parallel-group RCT with authors identified in the RCTs eligible for two systematic reviews. The authors were randomly allocated to the intervention (financial incentive with several contact approaches) or control group (using the same contact approaches). Studied outcomes: proportion of authors who provided IPD, time to obtain IPD, and completeness of IPD received. RESULTS: Of the 129 authors contacted, 37 authors suggested or contacted a person/funder providing relevant details or showed interest to collaborate, while 45 authors directed us to contact a person/funder, lacked resources/time, did not have ownership/approval to share the IPD, or claimed IPD was too old. None of the authors shared their IPD. We contacted 17 sponsors and received two complete IPD datasets from one sponsor. The time to obtain IPD was >1 year after a sponsor's positive response. Common barriers included study identification, data ownership, limited data access, and required IPD licenses. CONCLUSIONS: IPD sharing may depend on study characteristics, including funding type, study size, study risk of bias, and treatment effect, but not on providing a financial incentive. TRIAL REGISTRATION: Clinical Trials.gov (NCT02569411), registered on October 5th, 2015

The final transformation of Étaín

Abstract Background Although serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions Most 5-HT3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting. Trial registration This study was registered at PROSPERO: ( CRD42013003564 )

Contacting authors to retrieve individual patient data : study protocol for a randomized controlled trial

BACKGROUND: Individual patient data (IPD) meta-analysis is considered the "gold standard" for exploring the effectiveness of interventions in different subgroups of patients. However, obtaining IPD is time-consuming and contact with the researchers responsible for the original trials is usually required. To date, there are no studies evaluating different strategies to optimize the process for retrieval of IPD from such researchers. Our aim is to examine the impact of providing incentives to the researchers responsible for the trials eligible for a meta-analysis to submit their IPD. METHODS/DESIGN: We updated our previously published systematic reviews for type 1 diabetes mellitus comparing long- and intermediate-acting insulin regimens (from January 2013 to June 2015) and for Alzheimer's dementia comparing cognitive enhancers (from January 2015 to May 2015). Eligible were randomized controlled trials (RCTs) fulfilling the eligibility criteria of the systematic reviews. We will randomly allocate authors of the reports of these RCTs into an intervention or control group. Those allocated to the intervention group will be contacted by email, mail, and phone, and will be asked to provide the IPD from their RCT and will be given a financial incentive. Those allocated to the control group will be contacted by email, mail, and phone, but will not receive a financial incentive. Our primary outcome will be the proportion of authors who provide the IPD. The secondary outcomes will be the time to return the dataset (defined as the period between the information request and the authors' response with the dataset), and completeness of data. We will compare the response rates in the two groups using the odds ratio and the corresponding 95 % confidence interval. We will also use binary logistic regression and cox regression analyses to examine whether different RCT characteristics, such as study size and sponsor information, influence the probability of providing IPD and the time needed to share the data. DISCUSSION: This study will determine whether a financial incentive affects response rates when seeking IPD from the original researchers. We will disseminate our findings in an open access scientific journal and present results at national and international conferences. TRIAL REGISTRATION: This trial is registered in Clinical Trials.gov, ID number NCT02569411 . Date of registration 5 October 2015

Effectiveness of different compression-to-ventilation methods for cardiopulmonary resuscitation : a systematic review

Aim: To compare the effectiveness of different compression-to-ventilation methods during cardiopulmonary resuscitation (CPR) in patients with cardiac arrest. Methods: We searched MEDLINE and Cochrane Central Register of Controlled Trials from inception until January 2016. We included experimental, quasi-experimental, and observational studies that compared different chest compression-to-ventilation ratios during CPR for all patients and assessed at least one of the following outcomes: favourable neurological outcomes, survival, return of spontaneous circulation (ROSC), and quality of life. Two reviewers independently screened literature search results, abstracted data, and appraised the risk of bias. Random-effects meta-analyses were conducted separately for randomised and non-randomised studies, as well as study characteristics, such as CPR provider. Results: After screening 5703 titles and abstracts and 229 full-text articles, we included 41 studies, of which 13 were companion reports. For adults receiving bystander or dispatcher-instructed CPR, no significant differences were observed across all comparisons and outcomes. Significantly less adults receiving bystander-initiated or plus dispatcher-instructed compression-only CPR experienced favourable neurological outcomes, survival, and ROSC compared to CPR 30:2 (compression-to-ventilation) in un-adjusted analyses in a large cohort study. Evidence from emergency medical service (EMS) CPR providers showed significantly more adults receiving CPR 30:2 experiencing improved favourable neurological outcomes and survival versus those receiving CPR 15:2. Significantly more children receiving CPR 15:2 or 30:2 experienced favourable neurological outcomes, survival, and greater ROSC compared to compression-only CPR. However, for children <1 years of age, no significant differences were observed between CPR 15:2 or 30:2 and compression-only CPR. Conclusions: Our results demonstrated that for adults, CPR 30:2 is associated with better survival and favourable neurological outcomes when compared to CPR 15:2. For children, more patients receiving CPR with either 15:2 or 30:2 compression-to ventilation ratio experienced favourable neurological function, survival, and ROSC when compared to CO-CPR for children of all ages, but for children <1 years of age, no statistically significant differences were observed

Safety, effectiveness, and cost of long-acting versus intermediate-acting insulin for type 1 diabetes: Protocol for a systematic review and network meta-analysis

Abstract Background Type 1 diabetes mellitus (T1DM) causes progressive destruction of pancreatic beta cells leading to absolute insulin deficiency. Treatment of T1DM requires insulin, and some evidence suggests that longer acting insulin analogues might have a higher effectiveness and greater safety profile compared to intermediate-acting insulin. Our objective is to evaluate the comparative effectiveness, safety, and cost of long-acting insulin versus intermediate-acting insulin through a systematic review and network meta-analysis. Design/methods Studies examining long-acting versus intermediate-acting insulin or placebo preparations for adult T1DM patients will be included. The primary outcome is glycosylated hemoglobin (A1C), and secondary outcomes include emergency department and physician visits, hospital admissions, weight gain, quality of life, microvascular complications (e.g., retinopathy), macrovascular complications (e.g., cardiovascular disease), all-cause mortality, incident cancers, and cost. We will include experimental [randomized clinical trials (RCTs), quasi-RCTs, non-RCTs], quasi-experimental (controlled before-after, interrupted time series), observational (cohort), and cost studies, of any duration of follow-up, conducted during all time periods, and disseminated in any language. We will conduct comprehensive searches of electronic databases from inception onwards, including MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. We will also search for difficult to locate and unpublished literature by searching dissertation databases, public health organization websites, and trial registries. After a calibration exercise using our eligibility criteria and data abstraction forms, two reviewers will screen all citations, full-text articles, and abstract data in duplicate. Conflicts will be resolved by team discussion. Using a similar process, the Cochrane Effective Practice and Organization of Care Risk of Bias tool will be used to appraise the risk of bias of experimental and quasi-experimental studies, while the Newcastle Ottawa Scale will be used to assess the methodological quality of cohort studies. If feasible and appropriate, we will conduct a random effects meta-analysis, as well as a network meta-analysis. Discussion Our systematic review will be of utility to healthcare providers, policy-makers, T1DM patients and family members regarding treatment options of long-acting versus intermediate-acting insulin preparations. Systematic review registration PROSPERO registry number: CRD4201300361

Sustainability of knowledge translation interventions in healthcare decision-making: a scoping review

Abstract Background Knowledge translation (KT, also known as research utilization, and sometimes referring to implementation science) is a dynamic and iterative process that includes the synthesis, dissemination, exchange, and ethically sound application of knowledge to improve health. A KT intervention is one which facilitates the uptake of research. The long-term sustainability of KT interventions is unclear. We aimed to characterize KT interventions to manage chronic diseases that have been used for healthcare outcomes beyond 1 year or beyond the termination of initial grant funding. Methods We conducted a scoping review by searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Campbell from inception until February 2013. We included experimental, quasi-experimental, and observational studies providing information on the sustainability of KT interventions for managing chronic diseases in adults and focusing on end-users including patients, clinicians, public health officials, health service managers, and policy-makers. Articles were screened and abstracted by two reviewers, independently. The data were charted and results described narratively. Results We included 62 studies reported in 103 publications (total 260,688 patients) plus 41 companion reports after screening 12,328 titles and abstracts and 464 full-text articles. More than half of the studies were randomized controlled trials (RCTs). The duration of the KT intervention ranged from 61 to 522 weeks. Nine chronic conditions were examined across the studies, such as diabetes (34 %), cardiovascular disease (28 %), and hypertension (16 %). Thirteen KT interventions were reported across the studies. Patient education was the most commonly examined (20 %), followed by self-management (17 %). Most studies (61 %) focused on patient-level outcomes (e.g. disease severity), while 31 % included system-level outcomes (e.g. number of eye examinations), and 8 % used both. The interventions were aimed at the patient (58 %), health system (28 %), and healthcare personnel (14 %) levels. Conclusions We found few studies focusing on the sustainability of KT interventions. Most of the included studies focused on patient-level outcomes and patient-level KT interventions. A future systematic review can be conducted of the RCTs to examine the impact of sustainable KT interventions on health outcomes

Variability in the validity and reliability of outcome measures identified in a systematic review to assess treatment efficacy of cognitive enhancers for Alzheimer's Dementia.

IntroductionSelection of optimal outcome measures is a critical step in a systematic review; inclusion of uncommon or non-validated outcome measures can impact the uptake of systematic review findings. Our goals were to identify the validity and reliability of outcome measures used in primary studies to assess cognition, function, behaviour and global status; and, to use these data to select outcomes for a systematic review (SR) on treatment efficacy of cognitive enhancers for Alzheimer's Dementia (AD).MethodsArticles fulfilling the eligibility criteria of the SR were included in a charting exercise to catalogue outcome measures reported. Outcome measures were then assessed for validity and reliability. Two independent reviewers abstracted data on outcome measures and validity and reliability reported for cognition, function, behaviour and global status.Results129 studies were included in the charting exercise; 57 outcome measures were identified for cognition, 21 for function, 13 for behaviour and 10 for global status. A total of 35 (61%) cognition measures, 10 (48%) functional measures, 8 (61%) behavioural measures and four (40%) of global status measures were only used once in the literature. Validity and reliability information was found for 51% of cognition measures, 90% of function and global status measures and 100% of behavioural measures.ConclusionsWhile a large number of outcome measures were used in primary studies, many of these were used only once. Reporting of validity and reliability varied in AD studies of cognitive enhancers. Core outcome sets should be used when available; when they are not available researchers need to balance frequency of reported outcome measures, their respective validity and reliability, and preferences of knowledge users.Systematic review registrationCRD#42012001948