Reports Of Randomized Controlled Trials Research Articles

Reporting quality and adherence of randomized controlled trials about statins and/or fibrates for diabetic retinopathy to the CONSORT checklist

BackgroundA considerable amount of randomized controlled trials (RCTs) have been published on statins and/or fibrates for diabetic retinopathy, a clinical condition associated with high social and economic burden. Adherence to the CONSORT statement items is imperative to ensure transparency and reproducibility in clinical research. The aim of this study is to assess the reporting quality and the adherence to CONSORT of RCTs assessing statins and/or fibrates for diabetic retinopathy.MethodsWe conducted a critical appraisal study at Discipline of Evidence-based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp). A sensitive literature search was performed to identify all relevant RCTs, with no time or language limits. Two authors independently evaluated the reporting quality of the selected RCTs using the CONSORT statement as a standard.ResultsThirteen reports of RCTs were included in this study. The adherence of the reports to CONSORT items ranged from 24% to 68%. The median score was 11 (interquartile range (IQR) 8 to 13). When analyzed separately, the methods sections of the reports had a median of three items (IQR 2 to 4) judged adherent to the methods items of CONSORT (items 3 to 12). The most underreported items were those related to trial design, title and abstract, allocation concealment, implementation of the randomization sequence, and blinding. Other important items, such as the one related to the description of the inclusion criteria, also had low adherence.ConclusionsThe overall adherence to the CONSORT checklist items was poor, especially in the items related to the methods section. RCT reports on statins and/or fibrates for diabetic retinopathy must be optimized to avoid reporting biases and to improve transparency and reproducibility.

Reporting and interpretation of results from clinical trials that did not claim a treatment difference: survey of four general medical journals

ObjectivesTo describe and summarise how the results of randomised controlled trials (RCTs) that did not find a significant treatment effect are reported, and to estimate how commonly trial reports make...

Rates of retention of persons with a mental health disorder in outpatient smoking cessation and reduction trials, and associated factors: protocol for a systematic review and meta-analysis

IntroductionSmoking among persons with a mental health disorder is associated with inequitable health, social and economic burden. Randomised controlled trials (RCTs) are considered the gold standard design for the assessment...

External validity of randomized controlled trials of interventions in venous leg ulceration: A systematic review.

We set out to evaluate quality of reporting of data related to external validity from randomized controlled trials (RCTs) assessing treatment interventions for active venous leg ulcers. Using a systematic review study design, we identified 144 full-text RCTs of treatment interventions, where the wound was assessed and published in English from 1998 to 2018. We found that the median study sample size was 75.5. Weighted mean wound size was 13.22 cm2 and weighted mean wound duration was 22.20 months. Forty-six (32%) reported numbers screened for eligibility and 27 (19%) reported the number who declined to participate; 19 (13%) reported on patient ethnicity; 60 (42%) reported comorbidities; and 5 (4%) reported current medication use. When reported, 60/102 (59%) excluded patients with an ankle-brachial pressure index <0.8; 68/135 (50%) were conducted in Europe, 6/135 (4%) in Asia, and 74/104 (71%) were conducted in outpatient facilities; 3 (2%) reported socioeconomic factors and 88 (61%) reported on adverse events. We concluded that there is inadequate reporting of data related to external validity in reports of RCTs assessing venous leg ulcers treatment interventions. Significant variability exists in the ankle-brachial pressure index cutoff point for inclusion or exclusion, making generalizability difficult to assess.

A guidance was developed to identify participants with missing outcome data in randomized controlled trials

Background and ObjectivesIn order for authors of systematic reviews to address missing data in randomized controlled trials (RCTs), they need to first identify the number of trial participants with missing data. The objective of this study was to provide guidance for authors of systematic reviews on how to identify participants with missing outcome data in reports of RCTs. MethodsGuidance statements were informed by a review of studies addressing the topic of missing data and an iterative process of feedback and refinement, through meetings involving experts in health research methodology and authors of systematic reviews. ResultsThe proposed guidance includes (1) definitions of key terms, (2) 19 categories of participants described in RCT reports and who might have missing data, and (3) a flowchart on how to judge the outcome data missingness for each category. The judgment of missingness relies on how trial authors report on the categories and handle them in their analyses. Practically, for their primary analysis, systematic review authors should choose how to identify participants with missing outcome data (i.e., use either “definitely missing data” or “total possible missing data”), then select a method for handling missing data in meta-analysis. Sensitivity analyses should be undertaken to explore consistency with competing options for classifying patients as having missing data. ConclusionAdopting the proposed guidance will help promote transparency and consistency regarding how missing data are managed in systematic reviews.

Development of a search filter to identify reports of controlled clinical trials within CINAHL Plus.

Evidence synthesis reviews in health care rely on the efficient identification of research evidence, particularly evidence from randomised controlled trials (RCTs). There are no recently validated filters to identify RCTs in the Cumulative Index to Nursing and Allied Health Literature (CINAHL Plus). To develop, test and validate a search filter to identify reports of RCTs from CINAHL Plus. Nine sets of relevant and irrelevant records were identified to develop and test search filters iteratively. Two sets were used to validate the sensitivity and precision of the filters. The performance of two previously published filters and the filter built into EBSCOhost was evaluated. We present a validated filter which offers sensitivity of 0.88 (95% CI: 0.77-0.95) and precision of 0.36 (95% CI: 0.31-0.41). This is comparable to the sensitivity of published filters, but has much better precision. A sensitive and precise filter, developed using records selected based on title and abstract information, is available for identifying reports of RCTs in the CINAHL Plus database via EBSCOhost. Using this filter is likely to reduce the number of results needing to be screened to a quarter of those retrieved by other published filters.

Analysis and reporting of adverse events in randomised controlled trials: a review.

ObjectiveTo ascertain contemporary approaches to the collection, reporting and analysis of adverse events (AEs) in randomised controlled trials (RCTs) with a primary efficacy outcome.DesignA review of clinical trials of drug interventions from four high impact medical journals.Data sourcesElectronic contents table of the BMJ, the Journal of the American Medical Association (JAMA), the Lancet and the New England Journal of Medicine (NEJM) were searched for reports of original RCTs published between September 2015 and September 2016.MethodsA prepiloted checklist was used and single data extraction was performed by three reviewers with independent check of a randomly sampled subset to verify quality. We extracted data on collection methods, assessment of severity and causality, reporting criteria, analysis methods and presentation of AE data.ResultsWe identified 184 eligible reports (BMJ n=3; JAMA n=38, Lancet n=62 and NEJM n=81). Sixty-two per cent reported some form of spontaneous AE collection but only 29% included details of specific prompts used to ascertain AE data. Numbers that withdrew from the trial were well reported (80%), however only 35% of these reported whether withdrawals were due to AEs. Results presented and analysis performed was predominantly on ‘patients with at least one event’ with 84% of studies ignoring repeated events. Despite a lack of power to undertake formal hypothesis testing, 47% performed such tests for binary outcomes.ConclusionsThis review highlighted that the collection, reporting and analysis of AE data in clinical trials is inconsistent and RCTs as a source of safety data are underused. Areas to improve include reducing information loss when analysing at patient level and inappropriate practice of underpowered multiple hypothesis testing. Implementation of standard reporting practices could enable a more accurate synthesis of safety data and development of guidance for statistical methodology to assess causality of AEs could facilitate better statistical practice.

Control Groups in RCTs of Psychoeducational Palliative Care Interventions: A Systematic Review (S830)

1.Explain the purpose of a control group that is neither usual care nor no-treatment.2.Describe the current practice using control groups that are neither usual care nor no-treatment in RCTs of psychoeducational palliative care interventions.3.Compare the explanations of the active intervention and the more-than-usual-care control in trial reports of RCTs of psychoeducational palliative care interventions. In randomized controlled trials (RCTs) an active intervention’s efficacy is determined relative to a control condition; thus the control condition’s design is as important as the intervention’s. In RCTs of psychoeducational palliative care interventions, researchers often use a control condition that is neither usual care nor no-treatment, but little is known about the extent of research practices in designing such control conditions. Therefore, this study examined: 1) the current research practice using control conditions that are neither usual care nor no-treatment controls in RCTs of psychoeducational palliative care interventions, and 2) the rationale and completeness of the description of those control conditions in trail reports. PubMed, Embase, PsychINFO, and Web of Science were searched. The final sample included nine trial reports. For quality assessment, a modified Delphi list was used. The descriptions of both the active interventions and the control conditions were assessed using a modified version of Schulz et al's Intervention Taxonomy checklist. Four trials used attention controls designed to be equivalent to the structure of the active interventions. An additional four trials used a control condition with some aspects of attention control, but neither the amount nor the intensity of attention were similar to the intervention. Only three trial reports stated the rationale for choice of control conditions. Most reports contained delivery mode, materials, duration, frequency, and sequence of both the intervention and control conditions; but none described the qualifications or training required to deliver the control condition. Only one report mentioned the fidelity monitoring method, and no report included fidelity monitoring data. Our review of RCTs in psychoeducational palliative care interventions calls for researchers’ attention to appropriate selection, design, conduct and report of control conditions.

The quality of reporting randomized controlled trials in the dermatology literature in an era where the CONSORT statement is a standard.

The quality of reporting randomized controlled trials (RCTs) in the dermatology literature has not received much consideration since the late 2000s. We aimed to assess the quality of recently reported RCTs published in dermatology journals, focusing on randomization processes, blinding and trial registration. We reviewed 2042 original articles and identified 141 primary reports of RCTs in four dermatology journals (Journal of the American Academy of Dermatology, JAMA Dermatology, Journal of Investigative Dermatology and British Journal of Dermatology) from January 2015 to December 2017. Details were extracted from articles, supplements and public trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with optimal reporting quality. Among the 141 RCTs, 99 (70·2%), 82 (58·2%) and 69 (48·9%) described methods used for randomization, allocation concealment and implementation, respectively. Most trials (126, 89·4%) reported blinding status; however, one-third did not state the similarity of the intervention. Furthermore, 52 RCTs (36·9%) were not registered prospectively. Trials published in the British Journal of Dermatology and using central randomization were significantly associated with optimal reporting quality after adjusting for covariates. Several critical items in reporting RCTs, including allocation concealment, similarity of interventions in blinded trials and prospective trial registration, have remained unsatisfactory in the recent dermatology literature.

Comparison of the efficacy and safety of drug therapies for macular edema secondary to central retinal vein occlusion

ObjectivesTo evaluate the efficacy and safety of anti-vascular endothelial growth factor (VEGF) agents and corticosteroids for the treatment of macular oedema (ME) secondary to central retinal vein occlusion (CRVO).DesignSystematic review...

Hospitalisations and emergency department visits in cancer patients receiving systemic therapy: Systematic review and meta-analysis

Emergency department visits and hospitalisations (ED+H) during systemic therapy are undesirable for both patients and the health system. We undertook a systematic literature review and meta-analysis to evaluate the frequency of unplanned all-cause and treatment-related ED+H among adults receiving adjuvant or palliative-intent systemic therapy for all cancers. Randomised controlled trials (RCT) and observational studies (OS) reporting ED+H were identified from Medline and EMBASE from inception to June 2016. Quality was assessed using modified STROBE, CONSORT or PRISMA guidelines, depending on study type. A total of 112 OS (308,662 patients) and 26 RCTs (16,081 patients) met inclusion criteria. Most articles focused on palliative treatment (59%) delivered as first-line, in breast, lung and colorectal cancers. Only 20 articles reported ED frequency. Treatment-related and all-cause hospitalisations were more common in routine practice than in RCTs (29% vs. 16% and 42% vs. 28% respectively); frequency varied by treatment intent and tumour site. Methodological issues were common, particularly poor definition of the at-risk period. Hospitalisations are common, especially in unselected populations, but few articles report this and do so poorly. Routine, standardised reporting of ED+H during chemotherapy should be included in RCT reports and evaluated in routine care following adoption of new treatments.

Antigen-specific active immunotherapy for ovarian cancer.

This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials.gov (1966 to July 2009). We also conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For the first update of this review, we extended the searches to October 2013, and for this update, we extended the searches to July 2017. We searched for randomised controlled trials (RCTs), as well as non-randomised studies (NRSs), that included participants with epithelial ovarian cancer, irrespective of disease stage, who were treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, treatment schedule, and reported clinical or immunological outcomes. Two reviews authors independently extracted the data. We evaluated the risk of bias for RCTs according to standard methodological procedures expected by Cochrane, and for NRSs by using a selection of quality domains deemed best applicable to the NRS. We included 67 studies (representing 3632 women with epithelial ovarian cancer). The most striking observations of this review address the lack of uniformity in conduct and reporting of early-phase immunotherapy studies. Response definitions show substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events is frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack the relevant information necessary for risk of bias assessment. Therefore, we cannot rule out serious biases in most of the included trials. However, selection, attrition, and selective reporting biases are likely to have affected the studies included in this review. GRADE ratings were high only for survival; for other primary outcomes, GRADE ratings were very low.The largest body of evidence is currently available for CA-125-targeted antibody therapy (17 studies, 2347 participants; very low-certainty evidence). Non-randomised studies of CA-125-targeted antibody therapy suggest improved survival among humoral and/or cellular responders, with only moderate adverse events. However, four large randomised placebo-controlled trials did not show any clinical benefit, despite induction of immune responses in approximately 60% of participants. Time to relapse with CA-125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9 months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty evidence). Only one RCT provided data on overall survival, reporting rates of 80% in both treatment and placebo groups (three RCTs, 1062 participants; high-certainty evidence). Other small studies targeting many different tumour antigens have presented promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results and the limited side effects and toxicity reported, exploration of clinical efficacy in large well-designed RCTs may be worthwhile. We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously, as review authors found a significant dearth of relevant information for assessment of risk of bias in both RCTs and NRSs.

Effect and safety of combination lipid-lowering therapies based on statin treatment versus statin monotherapies on patients with high risk of cardiovascular events.

This study aimed to compare the effect and safety of statin monotherapies and combination therapies on lipid‐lowing therapies. We searched for published randomized controlled trial (RCT) reports of statin monotherapies and combination therapies in patients with high risk of cardiovascular events, and extracted lipid levels to perform meta‐analysis. A total of 12 RCT reports were included in this study. According to the new guidelines (low‐density lipoprotein cholesterol [LDL‐C] < 100 mg/dL, high‐density lipoprotein cholesterol [HDL‐C] > 130 mg/dL), the percent of LDL‐C attaining goals in combination therapy is more than that of monotherapy (risk ratio [RR] = 1.43, 95% confidence interval [CI]: 1.13 to 1.82, P = 0.003), and the percent of LDL‐C and HDL‐C attaining goals in combination therapy is greater than that of monotherapy (RR = 1.43, 95% CI: 1.24 to 1.65, P = 0.000). The changing level of blood lipid had significant statistical difference between the two groups. The degree of blood lipid lowered by combination therapy was larger than in monotherapy (standard mean difference [SMD] = −0.45, 95% CI: −0.75 to −0.14, P = 0.004; SMD = −0.72, 95% CI: 0.04 to 1.39, P = 0.039; and SMD = −0.71, 95% CI: −1.12 to −0.3, P = 0.001 in LDL‐C, HDL‐C, and triglyceride, respectively). The incidence of adverse events was not significantly different between the two groups (RR = 1.15, 95% CI: 0.91 to 1.37, P = 0.096; RR = 1.5, 95% CI: 0.55 to 4.1, P = 0.427; RR = 0.63, 95% CI: 0.33 to 1.24, P = 0.181 in incidence of total adverse events, drug‐related treatment, and myalgia, respectively). Combination therapy can bring better effect in reducing lipid. It does not increase the incidence of adverse events, so it can be used widely and safely.

Pneumococcal Disease and the Effectiveness of the PPV23 Vaccine in Adults: A Two-Stage Bayesian Meta-Analysis of Observational and RCT Reports

The efficacy of PPV-23 vaccine on outcomes of pneumococcal disease in adults still remains controversial due mainly to the lack of consistency between the results obtained from observational studies(OSs) and those obtained from randomized controlled trials(RCTs). As a consequence, the complexity in the structure of evidence available, in turn, generates a challenge for combining disparate pieces of evidence quantitatively. In this regard, we used a hierarchical Bayesian inference-based evidence synthesis of RCTs and observational data using a two-stage approach (in addition to a traditional random-effects meta-analysis) to examine the effectiveness of PPV-23 in adults. To this end, 21 studies were included involving 826109 adult participants. By a two-stage Bayesian meta-analysis, which was directly used for combining studies of different designs, the overall log OR (95% credible interval) for IPDs was −0.1048 (−0.3920,−0.0250), indicating a significant protective effect of the vaccination against IPDs. No significant effect of PPV-23 was found on all-cause pneumonia, pneumococcal pneumonia, and death from pneumonia, which confirmed the results obtained by a traditional method followed by stratified and sensitivity analyses. The estimated overall log OR (95% credible interval) was −0.0002 (−0.0241,0.0142), −0.0002 (−0.0110,0.0122), and −6.3912 × 10−5 (−0.0219,0.0131), respectively. The PPV-23 vaccine might be effective in preventing the most severe invasive forms of pneumococcal diseases, but not effective in preventing other clinical outcomes, in the adult population of 18 years and older.

Harms Reporting in Randomized Controlled Trials of Interventions Aimed at Modifying Microbiota: A Systematic Review.

Probiotics, prebiotics, and synbiotics are used increasingly, although the safety and potential harms of these interventions are poorly understood. To examine how harms-related information is reported in publications of randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics. Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (without language restrictions) from 1 January 2015 to 20 March 2018. RCTs assessing the safety or efficacy of at least 1 intervention involving probiotics, prebiotics, or synbiotics alone or in combination with another intervention compared with any control (such as a placebo or an antibiotic) for any clinical condition. 4 reviewers independently assessed study characteristics, the reporting of harms, and the presentation of safety results. Of 384 trials conducted in healthy volunteers (n= 136) or patients with any of several medical conditions (n= 248), 339 (88%) were published in specialty journals. Trials most often evaluated probiotics (n= 265 [69%]). Studies in persons with medical conditions enrolled outpatients (n= 195) and high-risk patients (n= 53). No harms-related data were reported for 106 trials (28%), safety results were not reported for 142 (37%), and the number of serious adverse events (SAEs) per study group was not given for 309 (80%). Of 242 studies mentioning harms-related results, 37% (n= 89) used only generic statements to describe AEs and 16% (n= 38) used inadequate metrics. Overall, 375 trials (98%) did not give a definition for AEs or SAEs, the number of participant withdrawals due to harms, or the number of AEs and SAEs per study group with denominators. Journal publication processes may have affected the completeness of reporting; only English-language publications were examined. Harms reporting in published reports of RCTs assessing probiotics, prebiotics, and synbiotics often is lacking or inadequate. We cannot broadly conclude that these interventions are safe without reporting safety data. No specific funding.

Imbalance p values for baseline covariates in randomized controlled trials: a last resort for the use of p values? A pro and contra debate.

BackgroundResults of randomized controlled trials (RCTs) are usually accompanied by a table that compares covariates between the study groups at baseline. Sometimes, the investigators report p values for imbalanced covariates. The aim of this debate is to illustrate the pro and contra of the use of these p values in RCTs.ProLow p values can be a sign of biased or fraudulent randomization and can be used as a warning sign. They can be considered as a screening tool with low positive-predictive value. Low p values should prompt us to ask for the reasons and for potential consequences, especially in combination with hints of methodological problems.ContraA fair randomization produces the expectation that the distribution of p values follows a flat distribution. It does not produce an expectation related to a single p value. The distribution of p values in RCTs can be influenced by the correlation among covariates, differential misclassification or differential mismeasurement of baseline covariates. Given only a small number of reported p values in the reports of RCTs, judging whether the realized p value distribution is, indeed, a flat distribution becomes difficult. If p values ≤0.005 or ≥0.995 were used as a sign of alarm, the false-positive rate would be 5.0% if randomization was done correctly, and five p values per RCT were reported.ConclusionUse of a low p value as a warning sign that randomization is potentially biased can be considered a vague heuristic. The authors of this debate are obviously more or less enthusiastic with this heuristic and differ in the consequences they propose.

Inclusion and exclusion criteria used in non-specific low back pain trials: a review of randomised controlled trials published between 2006 and 2012

BackgroundLow back pain is a common health complaint resulting in substantial economic burden. Each year, upwards of 20 randomised controlled trials (RCTs) evaluating interventions for non-specific low back pain are published. Use of the term non-specific low back pain has been criticised on the grounds of encouraging heterogeneity and hampering interpretation of findings due to possible heterogeneous causes, challenging meta-analyses. We explored selection criteria used in trials of treatments for nsLBP.MethodsA systematic review of English-language reports of RCTs in nsLBP population samples, published between 2006 and 2012, identified from MEDLINE, EMBASE, and the Cochrane Library databases, using a mixed-methods approach to analysis. Study inclusion and exclusion criteria were extracted, thematically categorised, and then descriptive statistics were used to summarise the prevalence by emerging category.ResultsWe included 168 studies. Two inclusion themes (anatomical area, and symptoms and signs) were identified. Anatomical area was most reported as between costal margins and gluteal folds (n = 8, 5%), while low back pain (n = 150, 89%) with or without referred leg pain (n = 27, 16%) was the most reported symptom. Exclusion criteria comprised 21 themes. Previous or scheduled surgery (n = 84, 50%), pregnancy (n = 81, 48%), malignancy (n = 78, 46%), trauma (n = 63, 37%) and psychological conditions (n = 58, 34%) were the most common. Sub-themes of exclusion criteria mostly related to neurological signs and symptoms: nerve root compromise (n = 44, 26%), neurological signs (n = 34, 20%) or disc herniation (n = 30, 18%). Specific conditions that were most often exclusion criteria were spondylolisthesis (n = 35, 21%), spinal stenosis (n = 31, 18%) or osteoporosis (n = 27, 16%).ConclusionRCTs of interventions for non-specific low back pain have incorporated diverse inclusion and exclusion criteria. Guidance on standardisation of inclusion and exclusion criteria for nsLBP trials will increase clinical homogeneity, facilitating greater interpretation of between-trial comparisons and meta-analyses. We propose a template for reporting inclusion and exclusion criteria.

Unbalanced rather than balanced randomized controlled trials are more often positive in favor of the new treatment: An exposed and non-exposed study

Clinical equipoise (i.e., uncertainty within the expert clinical community) is considered as a prerequisite for a randomized controlled trial (RCT). Indeed, a RCT must start with an “honest null hypothesis”, which indicates controversy in the clinical expert community about the superiority of one of the 2 compared interventions. At the planning stage, randomization may reflect the clinical uncertainty, namely, by the randomization ratio. A 1:1 ratio appears to best fit this state of uncertainty. We aimed to assess whether the clinical equipoise principle is satisfied in unbalanced RCTs (i.e., with an unequal probability of subjects being allocated to one group than another). Observational and comparative study between unbalanced and balanced RCTs. We searched the “core clinical journals” of MEDLINE to identify reports of two-parallel–group superiority unbalanced RCTs published between January 2009 and December 2010. For each unbalanced RCT, we identified a maximum of 4 reports (to maximize power) of matched balanced RCTs dealing with the same population. Our primary outcome was the proportion of positive RCTs (i.e., with statistically significant results for the primary outcome [ P < 0.05], showing greater efficacy with the new treatment than the control treatment). We selected 46 reports of unbalanced RCTs and 164 of balanced RCTs; 65.2% unbalanced RCTs and 43.9% of balanced RCTs were positive [odds ratio 2.38; 95% confidence interval: 1.23, 4.63]. As compared with balanced RCTs, unbalanced RCTs were more often industry-funded and their control treatments were more often inactive. Adjusting for these latter variables did not modify the results. This result questions the respect of clinical equipoise in unbalanced RCTs.

Surgical Treatment of Cervical Radiculopathy: Meta-analysis of Randomized Controlled Trials.

Meta-analysis of published randomized controlled trials (RCTs). To determine whether anterior cervical discectomy and fusion (ACDF), cervical disc replacement (CDR), or minimally invasive posterior cervical foraminotomy (MI-PCF) provides the best outcomes for patients with symptomatic single-level, single-side, and cervical radiculopathy. The surgical treatment of cervical radiculopathy is still controversial. ACDF has been widely used as a "gold standard." CDR has evolved and become a motion-preserving alternative with a potentially lower incidence of adjacent segment disease. However, both techniques require anterior neck dissection that carries a potential for serious morbidity. MI-PCF is a motion-preserving technique that can be performed with minimal invasiveness but has not gained universal acceptance. Electronic database search for RCTs comparing the efficacy and effectiveness of ACDF, CDR, and MI-PCF was performed. Meta-analysis was done for secondary surgical procedures and adverse events. A total of 358 studies were retrieved, of which four RCT reports met the inclusion criteria for this study. Three studies present clinical data comparing ACDF and CDR, and one study presents data comparing ACDF and MI-PCF. Available data from the RCTs analyzed concluded that ACDF, CDR, and MI-PCF result in significant improvements in relevant symptoms, clinical, and functional outcomes in patients with single-level, single side cervical radiculopathy refractory to nonoperative treatment. CDR had the lowest percentage of secondary surgical procedures (P = 0.0178) whereas MICPF had the lowest percentage of adverse events (P < 0.0001). All three techniques are effective in treating cervical radicular symptoms. MI-PCF has the lowest rate of adverse events whereas CDR has the lowest rate of secondary procedures. There is insufficient evidence to show which technique is the most effective and provides the longest-lasting symptom relief. 1.

Benzodiazepines as a Monotherapy in Depressive Disorders: A Systematic Review

Background: The aim of this paper was to perform a systematic review and, when feasible, a meta-analysis of randomized controlled trials (RCT) which used benzodiazepines (BZD) as a monotherapy versus placebo, antidepressant drugs (AD), or both. Methods: Keyword searches were conducted for identifying RCT comparing BZD and AD, and/or placebo in the treatment of depression, using electronic databases from their inception up to April 2017. We selected reports of RCT in which BZD were compared to AD and/or placebo in the treatment of adult patients with a primary diagnosis of depressive disorder or anxious depression. When feasible, data were subjected to meta-analysis. Results: A total of 38 studies met the criteria for inclusion and were then included in the systematic review. Only 1 study concerned a newer AD, fluvoxamine. For the meta-analysis, we submitted data on response rate from 22 RCT, considering BZD versus placebo (8 comparisons) and BZD versus tricyclic antidepressants (TCA) (20 comparisons). There was a lack of significant differences as to response rate between BZD and placebo, as well as between BZD and TCA. Analysis of individual studies disclosed that, in more than half of the studies comparing BZD to TCA and/or placebo, BZD were significantly more effective than placebo and as effective as TCA. Conclusions: BZD are a therapeutic option in anxious depression and there are no indications that AD are preferable. There is a pressing need for RCT of adequate methodological quality and follow-up comparing BZD to second-generation AD and placebo in anxious depression.