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Results for “Randomized trial”

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PubMed2005

Determinants of the intracluster correlation coefficient in cluster randomized trials: the case of implementation research.

The objective of this research was to identify determinants of the magnitude of intracluster correlation coefficients (ICCs) in cluster randomized trials from the field of implementation research. A survey of experts was conducted to generate a priori hypotheses of factors that might affect ICC size. Hypotheses were tested on empirical estimates of ICCs calculated from 21 implementation research datasets, mainly from the UK. Effects of setting (primary or secondary care), type of variable (process or outcome), type of measurement (objective or subjective), prevalence of outcome and size of cluster were tested. In total, 220 ICCs were available (range 0 to 0.415). Significant differences in ICC magnitude were found. The ICCs were significantly higher for process than for outcome variables, and for secondary care outcomes compared with primary care outcomes. The effects of prevalence and size were less clear cut. There was no evidence to suggest that type of measurement affected ICC size. In conclusion, accurate estimates of ICCs are essential for sample size calculations for cluster randomized trials of professional behaviour change interventions. This study demonstrates that ICCs are sensitive to a number of trial factors, particularly setting and outcome type. These factors must be considered when planning such cluster randomized trials.

Biomedical Research↗

PubMed2005

The use of random effects models to allow for clustering in individually randomized trials.

BACKGROUND: We describe different forms of clustering that may occur in individually randomized trials, where the observed outcomes for different individuals cannot be regarded as independent. We propose random effects models to allow for such clustering, across a range of contexts and trial designs, and investigate their effect on estimation and interpretation of the treatment effect. METHODS: We apply our proposed models to two individually randomized trials with potential for clustering, a trial of teleconsultation in hospital referral (the main outcome being offer of a further hospital appointment) and a trial of exercise therapy delivered by physiotherapists for low back pain (the outcome being a back pain score). Extensions to the methods include the possibility of explaining heterogeneity between clusters using cluster level characteristics and the potential dilution of cluster effects due to noncompliance. RESULTS: In the teleconsultation trial, the odds ratio was significant (1.52, 95% CI 1.27 to 1.82) when clustering was ignored, but smaller and nonsignificant (1.36, 95% CI 0.85 to 2.13) when clustering by hospital consultant was taken into account. The 95% range of estimated treatment effects across consultants was from 0.21 to 8.76. This variability was only partially explained by the specialty of the consultant. In the back pain trial, although there was an overall benefit of exercise (change of - 0.51 points on the back pain score) and little evidence of clustering, the estimated treatment effects for different physiotherapists ranged from -1.26 to +0.26 points. CONCLUSIONS: Clustering is an important issue in many individually randomized trials. Ignoring it can lead to underestimates of the uncertainty and too extreme P-values. Even when there is little apparent heterogeneity across clusters, it can still have a large impact on the estimation and interpretation of the treatment effect.

Back Pain↗

PubMed1995

Comparison and meta-analysis of randomized trials of endarterectomy for symptomatic carotid artery stenosis.

OBJECTIVE: Comparison and meta-analysis of randomized trials of carotid endarterectomy for symptomatic stenosis of the extracranial carotid artery. BACKGROUND: Randomized trials (North American Symptomatic Carotid Endarterectomy Trial [NASCET], the European Carotid Surgery Trial [ECST], and the VA Cooperative Study [VACS]) each show that carotid endarterectomy improves outcomes in selected symptomatic patients with high-grade extracranial carotid artery stenosis. Direct comparisons among the studies have not been possible because of differing methodologies, endpoints, and formats of data reporting. DESIGN/METHODS: Data for specified endpoints and corresponding person-years at risk were obtained for each trial. The rates of nonfatal stroke, nonfatal myocardial infarction, or death for surgically or medically treated patients in the perioperative period (30 days) and thereafter were compared (both including and excluding perioperative events) and then combined using meta-analytic techniques. Data from NASCET and ECST were also analyzed for differences in outcomes by sex. RESULTS: Event rate estimates (with 95% confidence intervals [95% CI]) for the first 30 days (events per person-year, primarily nonfatal stroke) for medically treated patients were 0.44 (0.22 to 0.76) for NASCET, 0.15 (0.04 to 0.38) for ECST, and 0.27 (0.03 to 0.96) for VACS. For surgically treated patients, the corresponding rates (per person-year) were 0.78 (0.49 to 1.19), 0.63 (0.41 to 0.94), and 1.27 (0.58 to 2.43). Event rates per year after 30 days were higher for medically treated patients (0.20 [0.16 to 0.25] versus 0.08 [0.05 to 0.11] for NASCET; 0.12 [0.10 to 0.15] versus 0.07 [0.06 to 0.09] for ECST; and 0.15 [0.07 to 0.25] versus 0.07 [0.03 to 0.16] for VACS). There were no significant differences among the trials, with an overall benefit for surgical therapy (risk ratio estimate, RR = 0.67, 95% CI = 0.54 to 0.83). There were no significant sex-based differences between NASCET and ECST and the overall benefit was not significantly different for men and women (RR = 0.58, 95% CI = 0.45 to 0.74 for men; RR = 0.84, 95% CI = 0.57 to 1.25 for women). CONCLUSIONS: Adjusting for primary endpoints and duration of follow-up, carotid endarterectomy has a similar benefit for symptomatic patients across trials and a similar benefit for men and women.

Aged↗

PubMed2005

Searching the LILACS database for Portuguese- and Spanish-language randomized trials in physiotherapy was difficult.

OBJECTIVE: Evidence-based practice requires access to systematic reviews and randomized controlled trials; however, most literature databases index primarily English-language journals. We sought to determine the extent and quality of Portuguese- and Spanish-language reports of randomized trials relevant to physiotherapy by searching the LILACS database (Literatura Latino Americana e do Caribe em Ciências da Saúde). A secondary aim was to compare the sensitivity of three strategies for searching for Portuguese- and Spanish-language randomized trials in physiotherapy. STUDY DESIGN AND SETTING: The LILACS database was searched for randomized trials using three search strategies. RESULTS: Three search strategies returned 5,262 records, of which only 47 were randomized trials. Most trials reported treatments for pain or cardiopulmonary disease, and most were of moderate to high quality. The sensitivity of the three search strategies varied from 2% to 53%. CONCLUSION: A small number of moderate- to high-quality randomized trials in physiotherapy are published in Spanish and Portuguese languages, but they are difficult to find.

Bibliometrics↗

PubMed2002

Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials.

OBJECTIVE: The antihypertensive effect of fish oil was estimated from randomized trials using metaregression analysis. Modification of the blood pressure (BP) effect by age, gender, blood pressure, and body mass index was examined. METHODS: A total of 90 randomized trials of fish oil and BP were identified through MEDLINE (1966-March 2001). Trials with co-interventions, patient populations, non-placebo controls, or duration of < 2 weeks were excluded. A total of 36 trials (50 strata) were included, 22 of which had a double-blind design. Original reports were retrieved for data collection on sample size, study design, duration, fish oil dose, BP changes and baseline characteristics of trial populations. Pooled BP estimates were obtained by metaregression analysis, weighted for trial sample sizes. Stratified analyses according to population characteristics were performed. RESULTS: Intake of fish oil was high in most trials (median dose: 3.7 g/day). Fish oil reduced systolic BP by 2.1 mmHg [95% confidence interval (CI): 1.0, 3.2; P < 0.01] and diastolic BP by 1.6 mmHg (95% CI: 1.0. 2.2; P < 0.01). Restricting the analysis to double-blind trials yielded BP reductions of 1.7 mmHg (95% CI: 0.3, 3.1) and 1.5 mmHg (95% CI: 0.6, 2.3), respectively. BP effects tended to be larger in populations that were older (> 45 years) and in hypertensive populations (BP >or= 140/90 mmHg). CONCLUSIONS: High intake of fish oil may lower BP, especially in older and hypertensive subjects. The antihypertensive effect of lower doses of fish oil (< 0.5 g/day) however, remains to be established.

Blood Pressure↗

PubMed1988

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Selecting patients for randomized trials: a systematic approach based on risk group.

BACKGROUND: A key aspect of randomized trial design is the choice of risk group. Some trials include patients from the entire at-risk population, others accrue only patients deemed to be at increased risk. We present a simple statistical approach for choosing between these approaches. The method is easily adapted to determine which of several competing definitions of high risk is optimal. METHOD: We treat eligibility criteria for a trial, such as a smoking history, as a prediction rule associated with a certain sensitivity (the number of patients who have the event and who are classified as high risk divided by the total number patients who have an event) and specificity (the number of patients who do not have an event and who do not meet criteria for high risk divided by the total number of patients who do not have an event). We then derive simple formulae to determine the proportion of patients receiving intervention, and the proportion who experience an event, where either all patients or only those at high risk are treated. We assume that the relative risk associated with intervention is the same over all choices of risk group. The proportion of events and interventions are combined using a net benefit approach and net benefit compared between strategies. RESULTS: We applied our method to design a trial of adjuvant therapy after prostatectomy. We were able to demonstrate that treating a high risk group was superior to treating all patients; choose the optimal definition of high risk; test the robustness of our results by sensitivity analysis. Our results had a ready clinical interpretation that could immediately aid trial design. CONCLUSION: The choice of risk group in randomized trials is usually based on rather informal methods. Our simple method demonstrates that this decision can be informed by simple statistical analyses.

Journal Article↗

PubMedDate not supplied

Analysis of variance is easily misapplied in the analysis of randomized trials: a critique and discussion of alternative statistical approaches.

Analysis of variance (ANOVA) is a statistical method that is widely used in the psychosomatic literature to analyze the results of randomized trials, yet ANOVA does not provide an estimate for the difference between groups, the key variable of interest in a randomized trial. Although the use of ANOVA is frequently justified on the grounds that a trial incorporates more than two groups, the hypothesis tested by ANOVA for these trials--"Are all groups equivalent?"--is often scientifically uninteresting. Regression methods are not only applicable to trials with many groups, but can be designed to address specific questions arising from the study design. ANOVA is also frequently used for trials with repeated measures, but the consequent reporting of "group effects," "time effects," and "time-by-group interactions" is a distraction from statistics of clinical and scientific value. Given that ANOVA is easily misapplied in the analysis of randomized trials, alternative approaches such as regression methods should be considered in preference.

Analysis of Variance↗

PubMedDate not supplied

Increasing fruit and vegetable consumption among callers to the CIS: results from a randomized trial.

BACKGROUND: Results are reported from a large randomized trial designed to increase fruit and vegetable consumption among callers to the Cancer Information Service (CIS). METHODS: CIS callers assigned to the intervention group received a brief proactive educational intervention over the telephone at the end of usual service, with two follow-up mailouts. Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention subjects. Subjects were interviewed by telephone at both 4-week (n = 1,672) and 4-month (n = 1,286) follow-up. RESULTS: A single-item measure of fruit and vegetable consumption revealed a significant intervention effect of approximately 0.65 servings per day at 4-week follow-up (P < 0.001) and 0.41 servings per day at 4-month follow-up (P < 0.001). Using a seven-item food frequency measure that was also included in the 4-month interviews, a similar intervention effect of 0.34 servings per day was obtained (P = 0.006). The vast majority of CIS callers (88%) endorsed the strategy of providing 5 A Day information proactively. CONCLUSIONS: A brief educational intervention delivered to CIS callers at the end of usual service was associated with an increase in self-reported fruit and vegetable intake.

Adult↗

PubMed1995

Long-term follow-up of mothers and their infants in a randomized trial on iron prophylaxis during pregnancy.

OBJECTIVE: A randomized trial comparing women who were given iron only if needed and those given iron prophylactically showed that routine prophylaxis is not crucial for mothers' or infants' health up to postpartum examination. This study investigated these infants' and mothers' subsequent health, as available in routine registers in a 7-year follow-up. STUDY DESIGN: Original data (N = 2693) were linked to the national population, birth, and hospital inpatient registers. RESULTS: The outcomes in the two groups were very similar: there were no statistically significant differences in deaths after birth, number or timing of infants' or mothers' hospitalizations, reasons for mothers' first hospitalization, number or timing of subsequent miscarriages or births, or problems or outcomes in the next birth. However, infants of the prophylactically supplemented group were more frequently hospitalized because of convulsions. CONCLUSION: This study does not support routine iron prophylaxis for well-nourished pregnant women.

Abortion, Spontaneous↗

PubMed1988

Implementation of the group sequential methodology in a randomized trial in metastatic colorectal carcinoma.

A prospective randomized trial using the group sequential statistical method with frequent planned interim analyses was initiated in patients with metastatic colorectal adenocarcinoma comparing methotrexate and 5 fluorouracil (MTX-FU) to methyl CCNU, vincristine, FU, and streptozotocin (MOF-Strep). As a requirement of the group sequential design, a p value of 0.0125 was necessary to stop the trial at the first analysis. The first analysis was done after 17 patients were entered in each study arm and revealed six partial responses to MOF-Strep (35%) and one partial response to MTX-FU (6%) (p = 0.017). As a result, patient accrual continued. Problems encountered with the implementation of the group sequential methodology and the importance of stratification for prognostic variables are discussed.

Adult↗

PubMed2001

Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials.

CONTEXT: Hormone replacement therapy (HRT) is widely considered to reduce fractures, but this belief is based on observational data; evidence from randomized trials is lacking. OBJECTIVE: To conduct a systematic review of all randomized trials of HRT that have reported or collected nonvertebral fracture data but that may not have focused on fracture prevention. DATA SOURCES: The MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trials Register databases were searched from 1997 through 2000 and a search was conducted of all recent systematic reviews to identify older studies. Authors were contacted to establish whether fracture data had been collected but not reported. Researchers in the field and pharmaceutical companies also were contacted to try to identify unpublished studies. STUDY SELECTION: Trials were included in which participants had been randomized to at least 12 months of therapy and data on nonvertebral fractures at any other site and due to any cause were available. Of 70 initially identified studies, 22 were included in the analysis. DATA EXTRACTION: Both investigators extracted data independently and appraised trial quality according to the Jadad scale, which assesses the methods of randomization, concealment allocation, and reporting of withdrawals and dropouts. Disagreements were resolved by discussion. DATA SYNTHESIS: There was an overall 27% reduction in nonvertebral fractures in a pooled analysis (reduction favoring HRT in relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.94; P =.02). This effect was greater among women randomized to HRT who had a mean age younger than 60 years (RR, 0.67; 95% CI, 0.46-0.98; P =.03). Among women with a mean age of 60 years or older, there was a reduced effect (RR, 0.88; 95% CI, 0.71-1.08; P =.22). For hip and wrist fractures alone, the effectiveness of HRT appeared more marked (RR, 0.60; 95% CI, 0.40-0.91; P =.02), particularly for women younger than 60 years (RR, 0.45; 95% CI, 0.26-0.79; P =.005). CONCLUSIONS: Our meta-analysis of randomized controlled trials of HRT noted a statistically significant reduction in nonvertebral fractures. However, this effect may be attenuated in older women.

Aged↗

PubMed1997

High-Dose Chemotherapy in Adult Solid Tumors and Lymphoproliferative Disorders: The Need for Randomized Trials.

The demonstration of a dose-effect relationship in a wide spectrum of malignancies including solid tumors and lymphoproliferative disorders, along with the development of new techniques of hematopoietic stem cell support, have given rise to a growing interest for high-dose chemotherapy in recent years. Results in more than 3,000 patients included in nonrandomized trials have been reported in the literature. However, only nine randomized trials addressing the issue of the impact of high-dose chemotherapy on survival have been published: three in non-Hodgkin's lymphoma, one in multiple myeloma, two in metastatic breast cancer, one in germ-cell tumors, one in melanoma, and one in small-cell lung cancer. Firm, reliable conclusions can only be drawn from studies conducted in the salvage treatment of non-Hodgkin's lymphoma and in the first-line treatment of multiple myeloma: high-dose chemotherapy used in a consolidation setting after conventional chemotherapy leads to a survival advantage in chemosensitive patients. Promising but not firmly conclusive results were reported in metastatic breast cancer. The results of the sixteen ongoing randomized trials as well as studies addressing the issue of cost-effectiveness will be critical in establishing definite conclusions on the role of high-dose chemotherapy. With the exception of multiple myeloma and relapsed non-Hodgkin's lymphoma, there is no evidence for treating patients with high-dose chemotherapy outside randomized clinical trials.

Journal Article↗

PubMed1995

Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies.

BACKGROUND: Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. PATIENTS AND METHODS: 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. RESULTS: The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. CONCLUSIONS: Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.

Adult↗

PubMed2005

Reliability, effect size, and responsiveness of health status measures in the design of randomized and cluster-randomized trials.

BACKGROUND: New health status survey instruments are often described by their psychometric (measurement) properties, such as Validity, Reliability, Effect Size, and Responsiveness. For cluster-randomized trials, another important statistic is the Intraclass Correlation (ICC) for the instrument within clusters. Studies using better instruments can be performed with smaller sample sizes, but better instruments may be more expensive in terms of dollars, opportunity cost, or poorer data quality due to the response burden of longer instruments. METHODS: We defined the psychometric statistics in terms of a mathematical model, and examined the power of a two-sample test as a function of the test-retest Reliability, Effect Size, Responsiveness, and Intraclass Correlation of the instrument. We examined the "cost-effectiveness" of using a one-item versus a five-item measure of mental health status. FINDINGS: Under the standard model for measurement error, the psychometric statistics are all functions of the same error term. They are also functions of the setting in which they were estimated. In randomized trials, power is a function of Reliability and sample size, and a less reliable instrument can achieve the desired power if N is increased. In cluster-randomized trials, adequate power may be obtained by increasing the number of clusters per treatment group (and often the number of persons per cluster), as well as by choosing a more reliable instrument. The one-item measure of mental health status may be more cost-effective than the five-item measure in some situations. CONCLUSION: If the goal is to diagnose or refer individual patients, an instrument with high Validity and Reliability is needed. In settings where the sample sizes are large or can be increased easily, any valid instrument may be cost-effective. It is likely that many published values of psychometric statistics are accurate only in settings similar to that in which they were estimated.

Cost-Benefit Analysis↗

PubMed1991

Laparoscopic surgery in ectopic pregnancy. A randomized trial versus laparotomy.

A randomized, prospective clinical trial was conducted to compare the efficacy of laparoscopic treatment with conventional conservative abdominal surgery for tubal pregnancy. Entry criteria were: size of the ectopic gestation less than 4 cm, hemodynamic stability, accessibility for laparoscopic treatment and a trained laparoscopist on duty. There was no difference between the groups regarding gestational duration, size and location of the ectopic gestation, or the mean preoperative hCG values. The groups differed with respect to total operation time (73 min for the laparoscopy group vs. 88 min for the laparotomy group), hospital stay (2.2 vs. 5.4 days) and convalescence period (11 vs. 24 days). The rates of elimination of hCG was similar in the groups, and there were no statistical difference in the rate of second intervention.

Chorionic Gonadotropin↗

PubMed2026

Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. METHODS: Twenty-eight adults with TRD were randomized to six weeks of figure-8-coil iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) (n = 15) or H7-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) (n = 13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. RESULTS: Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for figure-8-coil iTBS and 50.0% for H7-coil rTMS (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. CONCLUSION: In this pilot trial, figure-8-coil iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group differences. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05902312).

Adult↗

PubMed2004

Outcome reporting bias in randomized trials funded by the Canadian Institutes of Health Research.

BACKGROUND: The reporting of outcomes within published randomized trials has previously been shown to be incomplete, biased and inconsistent with study protocols. We sought to determine whether outcome reporting bias would be present in a cohort of government-funded trials subjected to rigorous peer review. METHODS: We compared protocols for randomized trials approved for funding by the Canadian Institutes of Health Research (formerly the Medical Research Council of Canada) from 1990 to 1998 with subsequent reports of the trials identified in journal publications. Characteristics of reported and unreported outcomes were recorded from the protocols and publications. Incompletely reported outcomes were defined as those with insufficient data provided in publications for inclusion in meta-analyses. An overall odds ratio measuring the association between completeness of reporting and statistical significance was calculated stratified by trial. Finally, primary outcomes specified in trial protocols were compared with those reported in publications. RESULTS: We identified 48 trials with 68 publications and 1402 outcomes. The median number of participants per trial was 299, and 44% of the trials were published in general medical journals. A median of 31% (10th-90th percentile range 5%-67%) of outcomes measured to assess the efficacy of an intervention (efficacy outcomes) and 59% (0%-100%) of those measured to assess the harm of an intervention (harm outcomes) per trial were incompletely reported. Statistically significant efficacy outcomes had a higher odds than nonsignificant efficacy outcomes of being fully reported (odds ratio 2.7; 95% confidence interval 1.5-5.0). Primary outcomes differed between protocols and publications for 40% of the trials. INTERPRETATION: Selective reporting of outcomes frequently occurs in publications of high-quality government-funded trials.

Canada↗