Understanding explanatory and pragmatic trials: Examples from randomized controlled trials on vertebroplasty

ObjectivesTo better understand the explanatory–pragmatic distinction in the design and interpretation of randomized controlled trials (RCTs).MethodsWe review the explanatory–pragmatic distinction in clinical trial design. We use the PRECIS-2 tool to evaluate the trial design of selected RCTs on percutaneous vertebroplasty for osteoporotic vertebral compression fractures. We discuss difficulties in the selection of criteria and in the construction of PRECIS diagrams. We also examine how inconsistency in the selection of various items of trial design can cause confusion in the interpretation of results.ResultsThe selection of criteria and the scoring of multiple PRECIS domains were subjective and thus debatable. The pragmascope patterns of various vertebroplasty trials were heterogeneous. Many trials had both pragmatic and explanatory components. Some placebo-controlled trial goals seem to have been explanatory, but their design actually included enough pragmatic items such that the meaning of negative trial results remains ambiguous.ConclusionThe results of a trial cannot be interpreted without understanding the various design choices made along the explanatory-pragmatic spectrum.     

Systematic review of randomized clinical trials of surgical treatment for carpal tunnel syndrome

BACKGROUND: Carpal tunnel syndrome (CTS) is a common disorder for which several surgical treatment options are available. However, there is no consensus on the most effective method of treatment. The object of this systematic review is to compare the efficacy of the various surgical techniques in relieving the symptoms of CTS and promoting return to work and/or activities of daily living. METHODS: Computer-aided searches of Medline, EMBASE and the Cochrane Controlled Trials Register were conducted, together with reference checking. A rating system, based on the number of studies and their methodological quality and findings, was used to determine the strength of the available evidence for the efficacy of the treatment. RESULTS: Fourteen studies were included in the review. None of the alternatives to standard open carpal tunnel release (OCTR) seems to offer better relief of symptoms. There is conflicting evidence about whether endoscopic carpal tunnel release results in earlier return to work and/or activities of daily living. CONCLUSION: Standard OCTR is still the preferred method of treatment for CTS. It is just as effective as the alternatives, but is technically less demanding, so incurs a lower risk of complications and of added costs.     

The reporting of randomized clinical trials using a surgical intervention is in need of immediate improvement: a systematic review

OBJECTIVE: To assess the reporting of surgical interventions, care providers, and number of centers in randomized clinical trials. METHODS: Systematic review was performed to assess reports of randomized controlled trials assessing surgical procedure published in 2004. A standardized abstraction form was used to extract data. RESULTS: A total of 158 articles were included. Details on the intervention intended, such as the surgical procedure, were reported in 138 (87.3%) articles, anesthetic management in 56 (35.4%), preoperative care in 34 (15.2%), and postoperative care in 78 (49.4%). How the experimental surgical intervention was carried out was reported in 64 articles (40.5%). Most trials were conducted in single centers (n = 109, 69.0%). The setting was reported in only 11 articles, and the volume of interventions performed was only reported in 5. Selection criteria were reported for care providers in 64 articles (40.5%). The number of care providers performing the intervention was reported in 51 articles (32.2%). The quality of reporting was low as assessed by CLEAR NPT (a 10-items checklist specifically developed to assess the reporting quality of RCTs assessing nonpharmacologic treatment). CONCLUSIONS: Inadequate reporting on the management of the surgical procedure, care providers, and surgery center may introduce bias in RCTs of surgical interventions, making their results questionable. We recommend extending the CONSORT Statement to surgical interventions.     

手法治疗腰椎间盘突出症临床随机对照试验系统评价

目的:评价手法治疗腰椎间盘突出症的有效性和安全性,分析目前临床研究的现状。方法:检索PubMed、OVID、Cochrane图书馆、CBM-disc数据库、CNKI数据库、VIP数据库以及手工检索,共收集手法治疗腰椎间盘突出症文献832篇,其中8篇符合纳入研究标准。Cochrane系统评价手册进行质量评价,并对8篇文献采用RevMan4.2进行Meta分析。结果:纳入的8篇文献共911例患者。8篇文献的治愈率汇总合并OR为3.65,95%CI为[2.15,6.20];有效率汇总合并OR为3.56,95%CI为[2.35,5.38]。手法组对腰椎间盘突出症的治愈率、有效率明显优于其他疗法(除手法之外或药物、或牵引、或针灸、或微波热疗,以下简称"其他疗法")组(P0.01)。结论:目前纳入研究显示手法治疗腰椎间盘突出症安全、有效,手法对腰椎间盘突出症的治愈率、有效率优于其他疗法。但由于纳入文献的数量有限且质量不是很高,结论尚不确定,需高质量证据来进一步验证。     

Moderately hypofractionated post-operative radiation therapy for breast cancer: Systematic review and meta-analysis of randomized clinical trials

IntroductionWe provide a critical assessment regarding current evidence for the use of moderately hypofractionated irradiation for patients with breast cancer. The aim of the study was to summarize the available evidence regarding outcomes after moderately hypofractionated compared with conventional radiation doses in the post-operative treatment of patients with breast cancer.Material and methodsThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS databases were searched until March 25, 2021. All randomized phase 3 clinical trials that compared moderately hypofractionated with conventional radiation doses in the post-operative treatment of patients with breast cancer were selected. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.ResultsEight clinical trials satisfied the eligibility criteria and were the focus of the analysis. A total of 12,139 breast cancer patients was randomly assigned for moderately hypofractionated compared with conventional irradiation. Meta-analysis of the trials regarding local recurrence, loco-regional recurrence, disease-free survival, and overall survival outcomes did not demonstrate any significant difference between moderately hypofractionated irradiation and conventional radiation doses groups. The rate of severe side effects was low in both groups; acute and late side effects and cosmesis were similar or even tended to be lower after moderately hypofractionated than after conventional irradiation.ConclusionsModerately hypofractionated is at least as effective and safe as conventional radiation irradiation regimens and should be considered as a treatment option for most, if not all, breast cancer patients.     

Methods and design considerations for randomized clinical trials evaluating surgical or endovascular treatments for cerebrovascular diseases

OBJECTIVE: The results of clinical trials affect the practice of surgery and endovascular therapy for cerebrovascular diseases. The purpose of this report is to review the basic components of the designs and methods for randomized clinical trials and to describe the influence of those components on the interpretation of trial results. METHODS: The goal of an optimal clinical trial of a new procedure is to provide the most objective and rigorous evaluation of the safety and effectiveness of that procedure. Anything in the design, performance, or analysis that impairs such an assessment decreases the ability of the trial to achieve its goal and answer the research question. To highlight the components of a clinical trial, this report uses examples of Phase III clinical trials that have influenced the practice of cerebrovascular surgery and endovascular therapy in the past three decades, including the International Cooperative Study of Extracranial/Intracranial Arterial Anastomosis, the North American Symptomatic Carotid Endarterectomy Trial, the Asymptomatic Carotid Atherosclerosis Study, the Prolyse in Acute Cerebral Thromboembolism II study, and the International Subarachnoid Aneurysm Trial. RESULTS: The research question (objective) of the trial must be clearly defined, with an objective measure of efficacy and a specified quantitative difference to define the superiority of one intervention over another, in a relatively homogeneous patient population. Allocation concealment, randomization with or without stratification, and blinding (or masking) are important strategies to prevent differences in the study populations that could adversely affect the conclusions of the study. The primary end point must correspond to the specific aims of the trial. It should be objectively defined, quantifiable, reliable, and reproducible. Commonly defined end points in surgical trials include changes from baseline illness or disease severity scores, morbidity and mortality rates, and relative risks of reaching an end point with time. The statistical methods used for interim and final analyses are important. The effects of dropouts, crossovers, and missing data should be understood in the context of the final analysis. Additional concepts, such as intention-to-treat analysis and use of actual versus predicted outcomes, are important with respect to interpretation of the final results of the study. CONCLUSION: The neurosurgical and neuroendovascular communities are currently planning or conducting several clinical trials to evaluate new procedures for the treatment of cerebrovascular diseases. It is hoped that a better understanding of the components of clinical trials will facilitate the design and implementation of effective studies.     

手法治疗椎动脉型颈椎病临床随机对照试验的系统评价

目的:评价手法治疗椎动脉型颈椎病的安全性、有效性,分析目前临床治疗现状。方法:检索PubMed、OVID、Cochrane图书馆、CBM、CNKI、VIP等数据库以及手工检索,共收集手法治疗椎动脉型颈椎病的文献265篇,中文文献251篇,英文文献14篇,其中5篇符合纳入研究标准,全部为中文文献;Cochrane系统评价手册进行质量评价,并对5篇文献采用RevMan 4.2进行Meta分析。结果:纳入的5篇文献共736例患者。5篇文献的治愈率汇总合并OR为2.93,95%CI为[2.10,4.08];有效率汇总合并OR为3.99,95%CI为[2.47,6.44];手法对椎动脉型颈椎病的治愈率、有效率均明显优于其他疗法(除手法之外的治疗方法,如牵引、药物等)(P<0.01)。结论:目前所纳入研究结果显示手法治疗椎动脉型颈椎病安全、有效,手法对椎动脉型颈椎病的治愈率、有效率明显优于其他疗法;但由于纳入文献的数量有限且质量不是很高,结论尚不确定,因此需要多中心的临床随机对照且长时间随访的试验,进一步验证。     

Enrollment and reporting practices in pediatric general surgical randomized clinical trials: A systematic review and observational analysis

Background

Pediatric surgical randomized clinical trials (RCTs) are labor-intensive and costly. This systematic review investigated patient accrual and estimates of study duration in RCTs by interrogating enrollment and registration practices.

Systematic review of randomized trials comparing rubber band ligation with excisional haemorrhoidectomy

BACKGROUND AND METHOD: This review compares the two most popular treatments for haemorrhoids, namely rubber band ligation (RBL) and excisional haemorrhoidectomy. Randomized trials were identified from the major electronic databases. Symptom control, retreatment, postoperative pain, complications, time off work and patient satisfaction were assessed. Relative risk (RR) and weighted mean difference with 95 per cent confidence interval (c.i.) were estimated using a random-effects model for dichotomous and continuous outcomes respectively. RESULTS: Three trials met the inclusion criteria and all were of poor methodological quality. Complete remission of haemorrhoidal symptoms was better after haemorrhoidectomy (RR 1.68 (95 per cent c.i 1.00 to 2.83)). There was significant heterogeneity between the studies (I(2) = 90.5 per cent; P < 0.001). Fewer patients required retreatment after haemorrhoidectomy (RR 0.20 (95 per cent c.i 0.09 to 0.40)), but anal stenosis, postoperative haemorrhage and incontinence to flatus were more common with this operation. CONCLUSIONS: Haemorrhoidectomy produced better long-term symptom control in patients with grade III haemorrhoids, but was associated with more postoperative complications than RBL.     

Systematic review and meta‐analysis of randomized clinical trials comparing single‐incision versus conventional laparoscopic cholecystectomy

Background:

Single‐incision laparoscopic cholecystectomy (SILC) may offer advantages over conventional laparoscopic cholecystectomy (LC).

Methods:

MEDLINE, Embase, PubMed, CINAHL, Cochrane Central Register of Controlled Trials and the Cochrane Library were searched for randomized clinical trials on SILC versus LC until May 2012. Odds ratio (OR) and weight mean difference (WMD) were calculated with 95 per cent confidence intervals (c.i.) based on intention‐to‐treat analysis.

Results:

Thirteen randomized clinical trials included a total of 923 procedures. SILC had a higher procedure failure rate than LC (OR 8·16, 95 per cent c.i. 3·42 to 19·45; P < 0·001), required a longer operating time (WMD 16·55, 95 per cent c.i. 9·95 to 23·15 min; P < 0·001) and was associated with greater intraoperative blood loss (WMD 1·58, 95% of c.i. 0·44 to 2·71 ml; P = 0·007). There were no differences between the two approaches in rate of conversion to open surgery, length of hospital stay, postoperative pain, adverse events, wound infections or port‐site hernias. Better cosmetic outcomes were demonstrated in favour of SILC as measured by Body Image Scale questionnaire (WMD ? 0·97, 95% of c.i. ? 1·51 to ? 0·43; P < 0·001) and Cosmesis score (WMD ? 2·46, 95% of c.i. ? 2·95 to ? 1·97; P < 0·001), but this was based on comparison with procedures in which multiple and often large ports (10 mm) were used.

Conclusion:

SILC has a higher procedure failure rate with more blood loss and takes longer than LC. No trial was adequately powered to assess safety. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Systematic review of groin wound surgical site infection incidence after arterial intervention

The objectives were to determine the surgical site infection incidence (including superficial/deep) fter arterial intervention through non-infected groin incisions and identify variables associated with incidence. MEDLINE, EMBASE and CENTRAL databases were searched for randomised controlled trials and observational studies of adults undergoing arterial intervention through a groin incision and reported surgical site infection. Infection incidence was examined in subgroups, variables were subjected to meta-regression. One hundred seventeen studies reporting 65 138 groin incisions in 42 347 patients were included. Overall surgical site infection incidence per incision was 8.1% (1730/21 431): 6.3% (804/12 786) were superficial and 1.9% (241/12 863) were deep. Superficial infection incidence was higher in randomised controlled trials (15.8% [278/1762]) compared with observational studies (4.8% [526/11 024]); deep infection incidence was similar (1.7% (30/1762) and 1.9% (211/11 101) respectively). Aneurysmal pathology (β = −10.229, P < .001) and retrospective observational design (β = −1.118, P = .002) were associated with lower infection incidence. Surgical site infection being a primary outcome was associated with a higher incidence of surgical site infections (β = 3.429, P = .017). The three-fold higher incidence of superficial surgical site infection reported in randomised controlled trials may be because of a more robust clinical review of patients. These results should be considered when benchmarking practice and could inform future trial design.