High quality protocols facilitate proper conduct, reporting, and external review
 of clinical trials. However, the completeness of trial protocols is often
 inadequate. To help improve the content and quality of protocols, an
 international group of stakeholders developed the SPIRIT 2013 Statement
 (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT
 Statement provides guidance in the form of a checklist of recommended items to
 include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important
 information to promote full understanding of the checklist recommendations. For
 each checklist item, we provide a rationale and detailed description; a model
 example from an actual protocol; and relevant references supporting its
 importance. We strongly recommend that this explanatory paper be used in
 conjunction with the SPIRIT Statement. A website of resources is also available
 (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement,
 should help with the drafting of trial protocols. Complete documentation of key
 trial elements can facilitate transparency and protocol review for the benefit
 of all stakeholders.

https://www.bmj.com/content/bmj/346/bmj.e7586.full.pdf

SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

Objective: To identify interventions designed to improve recruitment to randomised controlled trials, and to quantify their effect on trial participation. Design: Systematic review. Data sources: The Cochrane Methodology Review Group Specialised Register in the Cochrane Library, MEDLINE, EMBASE, ERIC, Science Citation Index, Social Sciences Citation Index, C2-SPECTR, the National Research Register and PubMed. Most searches were undertaken up to 2010; no language restrictions were applied. Study selection: Randomised and quasi-randomised controlled trials, including those recruiting to hypothetical studies. Studies on retention strategies, examining ways to increase questionnaire response or evaluating the use of incentives for clinicians were excluded. The study population included any potential trial participant (eg, patient, clinician and member of the public), or individual or group of individuals responsible for trial recruitment (eg, clinicians, researchers and recruitment sites). Two authors independently screened identified studies for eligibility. Results: 45 trials with over 43 000 participants were included. Some interventions were effective in increasing recruitment: telephone reminders to non-respondents (risk ratio (RR) 1.66, 95% CI 1.03 to 2.46; two studies, 1058 participants), use of opt-out rather than opt-in procedures for contacting potential participants (RR 1.39, 95% CI 1.06 to 1.84; one study, 152 participants) and open designs where participants know which treatment they are receiving in the trial (RR 1.22, 95% CI 1.09 to 1.36; two studies, 4833 participants). However, the effect of many other strategies is less clear, including the use of video to provide trial information and interventions aimed at recruiters.

https://bmjopen.bmj.com/content/bmjopen/3/2/e002360.full.pdf

Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)60687-5.pdf

The systemic immune response to trauma: an overview of pathophysiology and treatment.

The influence of social networking sites on health behavior change: a systematic review and meta-analysis

Summary Background The role of adjuvant chemotherapy for patients with rectal cancer after preoperative (chemo)radiotherapy and surgery is uncertain. We did a meta-analysis of individual patient data to compare adjuvant chemotherapy with observation for patients with rectal cancer. Methods We searched PubMed, Medline, Embase, Web of Science, the Cochrane Library, CENTRAL, and conference abstracts to identify European randomised, controlled, phase 3 trials comparing observation with adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with non-metastatic rectal cancer. The primary endpoint of interest was overall survival. Findings We analysed data from four eligible trials, including data from 1196 patients with (y)pTNM stage II or III disease, who had an R0 resection, had a low anterior resection or an abdominoperineal resection, and had a tumour located within 15 cm of the anal verge. We found no significant differences in overall survival between patients who received adjuvant chemotherapy and those who underwent observation (hazard ratio [HR] 0·97, 95% CI 0·81–1·17; p=0·775); there were no significant differences in overall survival in subgroup analyses. Overall, adjuvant chemotherapy did not significantly improve disease-free survival (HR 0·91, 95% CI 0·77–1·07; p=0·230) or distant recurrences (0·94, 0·78–1·14; p=0·523) compared with observation. However, in subgroup analyses, patients with a tumour 10–15 cm from the anal verge had improved disease-free survival (0·59, 0·40–0·85; p=0·005, p interaction =0·107) and fewer distant recurrences (0·61, 0·40–0·94; p=0·025, p interaction =0·126) when treated with adjuvant chemotherapy compared with patients undergoing observation. Interpretation Overall, adjuvant fluorouracil-based chemotherapy did not improve overall survival, disease-free survival, or distant recurrences. However, adjuvant chemotherapy might benefit patients with a tumour 10–15 cm from the anal verge in terms of disease-free survival and distant recurrence. Further studies of preoperative and postoperative treatment for this subgroup of patients are warranted. Funding None.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(14)71199-4.pdf

Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Recruiting participants to trials can be extremely difficult. Identifying strategies that improve trial recruitment would benefit both trialists and health research. OBJECTIVES: To quantify the effects of strategies to improve recruitment of participants to randomised controlled trials. SEARCH STRATEGY: We searched the Cochrane Methodology Review Group Specialised Register - CMR (The Cochrane Library (online) Issue 1 2008) (searched 20 February 2008); MEDLINE, Ovid (1950 to date of search) (searched 06 May 2008); EMBASE, Ovid (1980 to date of search) (searched 16 May 2008); ERIC, CSA (1966 to date of search) (searched 19 March 2008); Science Citation Index Expanded, ISI Web of Science (1975 to date of search) (searched 19 March 2008); Social Sciences Citation Index, ISI Web of Science (1975 to date of search) (searched 19 March 2008); and National Research Register (online) (Issue 3 2007) (searched 03 September 2007); C2-SPECTR (searched 09 April 2008). We also searched PubMed (25 March 2008) to retrieve "related articles" for 15 studies included in a previous version of this review. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of methods to increase recruitment to randomised controlled trials. This includes non-healthcare studies and studies recruiting to hypothetical trials. Studies aiming to increase response rates to questionnaires or trial retention, or which evaluated incentives and disincentives for clinicians to recruit patients were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted on the method evaluated; country in which the study was carried out; nature of the population; nature of the study setting; nature of the study to be recruited into; randomisation or quasi-randomisation method; and numbers and proportions in each intervention group. We used risk ratios and their 95% confidence intervals to describe the effects in individual trials, and assessed heterogeneity of these ratios between trials. MAIN RESULTS: We identified 27 eligible trials with more than 26,604 participants. There were 24 studies involving interventions aimed directly at trial participants, while three evaluated interventions aimed at people recruiting participants. All studies were in health care. Some interventions were effective in increasing recruitment: telephone reminders to non-respondents (RR 2.66, 95% CI 1.37 to 5.18), use of opt-out, rather than opt-in, procedures for contacting potential trial participants (RR 1.39, 95% CI 1.06 to 1.84) and open designs where participants know which treatment they are receiving in the trial (RR 1.25, 95% CI 1.18 to 1.34). However, some of these strategies have disadvantages, which may limit their widespread use. For example, opt-out procedures are controversial and open designs are by definition unblinded. The effects of many other recruitment strategies are unclear; examples include the use of video to provide trial information to potential participants and modifying the training of recruiters. Many studies looked at recruitment to hypothetical trials and it is unclear how applicable these results are to real trials. AUTHORS' CONCLUSIONS: Trialists can increase recruitment to their trials by using the strategies shown to be effective in this review: telephone reminders; use of opt-out, rather than opt-in; procedures for contacting potential trial participants and open designs. Some strategies (e.g. open trial designs) need to be considered carefully before use because they also have disadvantages. For example, opt-out procedures are controversial and open designs are by definition unblinded.

/pdf/strategies-to-improve-recruitment-to-randomised-controlled-r5ah17iror.pdf

Strategies to improve recruitment to randomised controlled trials.

A criticism of Randomized Controlled Trials (RCTs) in primary care is that they lack external validity, participants being unrepresentative of the wider population. Our aim was to determine whether published primary care-based RCTs report information about how the study sample is assembled, and whether this is associated with RCT characteristics. We reviewed RCTs published in four primary care journals in the years 2001–2004. Main outcomes were: (1) eligibility fraction (proportion eligible of those screened), (2) enrolment fraction (proportion randomised of those eligible), (3) recruitment fraction (proportion of potential participants actually randomised), and (4) number of patients needed to be screened (NNS) in order to randomize one participant. A total of 148 RCTs were reviewed. One hundred and three trials (70%) reported the number of individuals assessed by investigators for eligibility, 119 (80%) reported the number eligible for participation, and all reported the actual number recruited. The median eligibility fraction was 83% (IQR 40% to 100%), and the median enrolment fraction was 74% (IQR 49% to 92%). The median NNS was 2.43, with some trials reportedly recruiting every patient or practice screened for eligibility, and one trial screening 484 for each patient recruited. We found no association between NNS and journal, trial size, multi- or single-centre, funding source or type of intervention. There may be associations between provision of sufficient recruitment data for the calculation of NNS and funding source and type of intervention. RCTs reporting recruitment data in primary care suggest that once screened for eligibility and found to match inclusion criteria patients are likely to be randomized. This finding needs to be treated with caution as it may represent inadequate identification or reporting of the eligible population. A substantial minority of RCTs did not provide sufficient information about the patient recruitment process.

/pdf/the-external-validity-of-published-randomized-controlled-1x0ua1340w.pdf

Ritu Jones

Papers

Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis

Strategies to improve recruitment to randomised controlled trials.

The external validity of published randomized controlled trials in primary care