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Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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At least 19 recordsLinked to original sources
PubMed1992

The selection of cases for randomised trials: a registry survey of concurrent trial and non-trial patients. The British Stomach Cancer Group.

A randomised trial of adjuvant chemotherapy vs placebo in operable stomach cancer recruited 249 patients from the West Midlands Region between 1976-1980. A Cancer Registry survey identified a further 1261 suitable concurrent cases. Trial patients were compared with the 960 non-trial cases from participating Districts. Only 493 (51%) non-trial cases passed all of the prospective trial selection criteria for entry. Stage and fitness caused the majority of exclusions and were also highly prognostic. A univariate analysis comparing eligible patients with the trial showed the two groups to be balanced for the significant independent prognostic factors of the trial. However, differences in patient age and the surgery performed indicate that recruitment may have been influenced by unknown selection factors. This survey highlights the difficulty of retrospective selection and confirms the need for randomised controls. Data available from specialist Registries may be used to help develop new protocols and to verify and extend trial results.

Adolescent↗
PubMed1989

Estimation of trial-to-trial variation in evoked potential signals by smoothing across trials.

Averaging single trial evoked potential data to produce an estimate of the underlying signal obscures trial-to-trial variation in the response. We describe a method for estimating slow changes in the evoked potential signal by smoothing the data over trials. We discuss the crucial issue of deciding how much to smooth and suggest that an appropriate smoothing parameter is one that minimizes the estimated mean average square error of the smoothed data. Equations to estimate the mean average square error for a one-dimensional local linear regression smoother are presented. Performance of the method is assessed using simulated evoked potential data with several different models of a changing signal and different values of the signal-to-noise ratio. We find that the method rarely imputes trial-to-trial variation to data sets that have an unchanging signal, while it almost always produces less error than averaging when estimating a varying signal. The ability of the method to reveal signal heterogeneity is hampered by very low signal-to-noise ratios. When applied to real auditory evoked potential data from a sample of elderly subjects, the method indicated a changing signal in 35% of all subjects and in 56% of subjects with signal-to-noise ratios above 0.6. Consistent patterns of variation in the auditory evoked potential were present in this sample.

Aged↗
PubMed1990

Mortality rates after 10.5 years for participants in the Multiple Risk Factor Intervention Trial. Findings related to a priori hypotheses of the trial. The Multiple Risk Factor Intervention Trial Research Group.

The Multiple Risk Factor Intervention Trial was a primary prevention trial to test the effect of multifactor intervention on coronary heart disease mortality in high-risk men who were randomly assigned to special intervention (n = 6428) or to their usual sources of health care (n = 6438). As previously reported, after 6 to 8 years of intervention, mortality from coronary heart disease and from all causes did not differ significantly between men assigned to special intervention and men assigned to their usual sources of health care. This report describes the mortality findings after 10.5 years (an average of 3.8 years after the end of intervention). Mortality rates were lower for men who received special intervention than for men who received their usual care by 10.6% for coronary heart disease and by 7.7% for all causes. Differences in mortality rates were substantially larger after the end of intervention than observed to that point. Differences in mortality rates after 10.5 years were primarily due to a 24% reduction in the death rate from acute myocardial infarction in men receiving special intervention compared with men receiving their usual care. As before, mortality differences between special intervention and usual care varied according to the presence of resting electrocardiographic abnormalities. These data suggest that multiple risk factor intervention confers a mortality benefit in middle-aged men over a period of about 10 years.

Adult↗
PubMed1987

Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial. Report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh.

In a trial that began in 1978, 1312 evaluable patients under 80 years of age who either had negative axillary nodes or were postmenopausal with positive axillary nodes were randomised to receive adjuvant tamoxifen 20 mg daily for 5 years, or tamoxifen for the treatment of first relapse. Estimates of oestrogen receptor (ER) content of primary tumour specimens were made in 57%. There has been a highly significant delay in relapse in the adjuvant arm of the trial. This benefit supersedes that from tamoxifen given as treatment for recurrent disease in control-arm patients (93% received this) so that benefit from adjuvant tamoxifen was maintained in the overall survival comparisons. This improvement seems to be independent of nodal and menopausal status. It does not differ significantly with ER level, although the greatest benefit in disease-free survival is in patients with levels of 100 fmol/mg protein or more.

Adult↗
PubMed1991

Verification of the cause of death in the trial of early detection of breast cancer. UK Trial of Early Detection of Breast Cancer Group. Trial Co-ordinating Centre.

The limitations of case review as a means of identifying errors in death certificates among breast cancer patients in a non-randomised trial of screening are illustrated by the findings of this large study. Records of 928 out of 990 deaths were available for review but were very variable in quality. Definite errors were found in 1%, errors were suspected in a further 5% and uncertainty about the cause of death, despite review, was recorded for 27%. The overall bias in reporting breast cancer deaths was less than 1%. It was concluded that the certified underlying cause of death without review provides an adequate endpoint for evaluating breast cancer screening programmes in the UK.

Age Factors↗
PubMed1992

The Lipid Research Clinics Coronary Primary Prevention Trial. Results of 6 years of post-trial follow-up. The Lipid Research Clinics Investigators.

BACKGROUND: Participants in the Lipid Research Clinics Coronary Primary Prevention Trial, a randomized, cholesterol-lowering trial comparing cholestyramine (N = 1907) vs placebo (N = 1899) treatment in 35- and 59-year-old asymptomatic hypercholesterolemic men, conducted between 1973 and 1983, were followed up annually from 1985 until 1989. Post-trial treatment was not provided. METHODS: Eleven predefined hypotheses pertaining to possible benefits and adverse effects of in-trial cholestyramine treatment were tested by standard statistical comparisons of the two original Coronary Primary Prevention Trial treatment groups (cholestyramine and placebo). RESULTS: Similar increasing proportions of cholestyramine and placebo used cholesterol-lowering drugs post-trial. After 13.4 years of in-trial plus post-trial follow-up, there were 13 (143 vs 156) fewer deaths in the cholestyramine group than in the placebo group. Although not statistically significant, the mortality hazard ratio (0.89) was similar to that in other cholesterol-lowering trials. This trend, a result of reduced coronary heart disease mortality, occurred despite a post-trial narrowing of the in-trial cholestyramine-placebo difference in coronary heart disease incidence from 32 (155 vs 187) to 16 (268 vs 284). The cholestyramine and placebo groups had similar 13.4-year mortality rates from cancer, other medical causes, and trauma and similar cancer incidence rates. However, 13.4-year incidences of benign colorectal tumors (50 vs 34), cancer of the buccal cavity and pharynx (eight vs two), gallbladder disease (68 vs 53), and gallbladder surgery (58 vs 40) were nonsignificantly increased in the cholestyramine group. CONCLUSION: Overall, 6 years of post-Coronary Primary Prevention Trial follow-up have not provided conclusive evidence of benefit or long-term toxicity of cholestyramine treatment beyond that evident at the cessation of the trial.

Cause of Death↗
PubMed1987

Two randomised phase II trials of intermittent intravenous versus subcutaneous alpha-2 interferon alone (trial 1) and in combination with 5-fluorouracil (trial 2) in advanced colorectal cancer.

Sixty-five patients with advanced colorectal cancer were randomised to one of two schedules of recombinant alpha-2 interferon (IFN). In the first study, 36 patients received single-agent IFN, either 50 X 10(6) U/m2 intravenously on 5 consecutive days every 4 weeks, or 20 X 10(6) U/m2 subcutaneously three times per week. No tumour responses were seen and toxicity was unacceptable. In the second study, 29 patients received IFN in two similar schedules, but the dose of IFN was reduced to 20 X 10(6) U/m2 per day in the intravenous arm and to 5 X 10(6) U/m2 per day in the subcutaneous arm. In addition these patients were administered intravenous 5-Fluorouracil (5-FU), 250-500 mg/m2 per day on the first 5 days of each 4-weekly cycle. Although the toxicity of this second study was tolerable, only one short-lived partial remission was observed. Alpha-2 interferon, alone or in combination with 5-FU, is ineffective in advanced colorectal cancer.

Adenocarcinoma↗
PubMed1985

Termination of clinical trials: the beta-blocker heart attack trial and the hypertension detection and follow-up program experience.

The close-out of clinical trials that end ahead of schedule often involves problems that differ from those of trials that end as planned. The Beta-Blocker Heart Attack Trial (BHAT), a double-blind study of 3837 post-myocardial infarction patients, was a multicenter clinical trial that ended early because therapeutic benefit had been demonstrated. The Hypertension Detection and Follow-up Program (HDFP), a randomized unblinded study of 10,940 hypertensive individuals, was a multicenter trial that ended as planned. Using these trials as illustrations, the issues arising in multicenter trials that end ahead of schedule are contrasted to those that arise in trials that end as scheduled. Close-out activities that are discussed include documentation of close-out procedures, release of trial information, preparation of trial participants and staff, ascertaining vital status, continuing patient care, data collection and coding, and publication of trial results. Because of the possibility a study might end early, advance planning for close-out is essential.

Adult↗
PubMed2026

Timing of OMERACT core domain measurement in gout clinical trials: a systematic review of randomised trials.

AIMS: The Outcome Measures in Rheumatology (OMERACT) initiative has endorsed core domain sets for gout trials. The aims of this study were to evaluate the time points and frequencies at which the gout core domains are measured in existing gout urate-lowering therapy and gout flare trials, and whether all collected measurements were reported. METHODS: Urate-lowering therapy (n = 29) and gout flare randomised clinical trials (n = 14) from 2005 were identified from a prior systematic review of core domain reporting. Data were extracted for the time points and frequencies at which each core domain was measured, as well as whether all collected measurements were reported. RESULTS: In urate-lowering therapy trials, the core domains were measured at seven different frequencies. Serum urate and gout flares were most commonly measured monthly, and tophus burden was most commonly measured three monthly. Reporting of all collected measurements varied, from 24/29 (83%) trials for serum urate to 0/2 (0%) trials for activity limitation. In gout flare trials, core domains were measured at nine different frequencies. Pain, joint tenderness and joint swelling were most commonly measured monthly. Reporting of all collected measurements varied, from 13/14 (93%) trials for pain to 3/8 (37.5%) trials for joint tenderness. CONCLUSION: In both urate-lowering therapy and gout flare trials, there is substantial variability in when the core domains are measured, and reporting of collected measurements is inconsistent. This work provides the foundation for a consensus process to establish standardised time points and frequencies for measuring the OMERACT-endorsed gout core domains.

Gout↗
PubMed1991

Aspects of the science of cancer prevention trials: lessons from the conduct and planning of clinical trials of a low-fat diet intervention among women.

Cancer prevention trials are contrasted with cancer therapy trials, cardiovascular disease prevention trials, epidemiologic cohort and case-control studies, and trials with surrogate endpoints, in order to highlight some of their unique features and in order to examine the role of such trials in the cancer prevention agenda. The implication of these features and this role are discussed with respect to trial rationale, trial design, and trial protocol, with planning exercises for proposed dietary fat intervention trials among women providing illustration. Finally, some considerations are mentioned for the planning of a primary prevention trial of breast cancer using tamoxifen.

Aged↗
PubMed1986

Ethics and errors of clinical trials and the role and place of different types of trial.

Controlled clinical trials, usually carried out in a multicentre, randomized manner, have become fashionable and popular because they contribute to the general acceptance of the results, particularly when the difference between the treatment arms is small. The present book and the present introduction attempt to discuss when and how this form of trial is appropriate. It is recognized that the discussion may be one-sided in the sense that the undoubted and well-known merits of controlled clinical trials are not reiterated. The focus of the present discussion is on the scientific, practical and ethical problems inherent in such trials and on possibilities for improving their design. In the future clinical trials should be used with more restraint than hitherto. Phase I trials should replace inter-patient by intra-patient dose escalation in order to give each patient a chance to benefit from the treatment. Since such trials frequently cause discomfort, they should be limited to one centre at a time. The number of patients subjected to phase II trials can be appreciably reduced if reasonable statistical measures are taken, as proposed here, to optimize and minimize the trial. Phase III trials must improve the relevance of the questions asked, reporting of errors, patient information and statistical interpretation. They must be based on promising phase II studies with historical controls so that their efficacy is increased.

Antineoplastic Agents↗
PubMed2026

Understanding randomized controlled trial generalizability through an embedded molecular diagnostics trial.

BACKGROUND: Issues with randomized controlled trial generalizability are well described, but whether these issues result from differences in patient treatment across contexts remains unknown. We studied treatment of patients with high-risk prostate cancer after radical prostatectomy inside and outside a randomized controlled trial evaluating the impact of a genomic classifier on post-radical prostatectomy treatment decision making (Genomics in Michigan Impacting Observation of Radiation [G-MINOR]; ClinicalTrials.gov identifier NCT02783950). METHODS: G-MINOR enrolled 338 patients; propensity score-matched eligible but unenrolled patient cohorts (pretrial and trial contemporary) from the Michigan Urological Surgery Improvement Collaborative (MUSIC), in which the trial was embedded, were compared for rates and time to secondary treatment (adjuvant or salvage therapy) after prostatectomy. RESULTS: Among 338 patients in the G-MINOR cohort, 69 (31 adjuvant, 38 salvage) received secondary treatment compared with 266 (183 adjuvant, 83 salvage) and 104 (60 adjuvant, 44 salvage) in the 1014 contemporary and 338 pretrial-matched MUSIC cohorts. Time to secondary treatment was much shorter in the MUSIC cohort across all comparisons. For example, matching G-MINOR to synchronous MUSIC patients demonstrated 84% vs 74% estimated 2-year treatment-free survival for trial and real-world patients, respectively (P&#x2009;<&#x2009;.001). CONCLUSIONS: Controlling for key clinicopathologic factors, patients in the G-MINOR randomized controlled trial and MUSIC cohorts were treated differently, even after stratifying by genomic risk. These findings suggest that challenges in randomized controlled trial generalizability extend beyond the representativeness of trial participants. Differences in management may also explain why divergent patient outcomes are observed in randomized controlled trials vs real-world settings.

Aged↗
PubMed1978

The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial. Survey of 71 "negative" trials.

Seventy-one "negative" randomized control trials were re-examined to determine if the investigators had studied large enough samples to give a high probability (greater than 0.90) of detecting a 25 per cent and 50 per cent therapeutic improvement in the response. Sixty-seven of the trials had a greater than 10 per cent risk of missing a true 25 per cent therapeutic improvement, and with the same risk, 50 of the trials could have missed a 50 per cent improvement. Estimates of 90 per cent confidence intervals for the true improvement in each trial showed that in 57 of these "negative" trials, a potential 25 per cent improvement was possible, and 34 of the trials showed a potential 50 per cent improvement. Many of the therapies labeled as "no different from control" in trials using inadequate samples have not received a fair test. Concern for the probability of missing an important therapeutic improvement because of small sample sizes deserves more attention in the planning of clinical trials.

Clinical Trials as Topic↗
PubMed1991

Monitoring a randomized clinical trial for futility: the north-Norwegian lidocaine intervention trial.

Randomized clinical trials of acute disease are usually designed as single-look, fixed sample size trials. This methodological study compares the conventional approach with a multiple-look, group sequential design with stopping rules for both treatment efficacy and for an inconclusive trial outcome, called trial futility. An ongoing trial on pre-hospital prophylaxis of sudden death in acute myocardial infarction forms the basis of the analysis. The effects of introducing multiple looks (or interim analyses) and tests for futility were obtained by binomial simulation. The introduction of four looks (that is, three interim and a final analysis) resulted in a modest increase in the maximal number of patients required. This was, however, fully compensated for by the high probability of early termination in case of treatment efficacy. The addition of futility tests, enabling termination at half the maximum trial size when there is no treatment difference, resulted in only a negligible reduction of overall power. We conclude that multiple-look, group sequential designs testing for both treatment efficacy and trial futility may improve the cost-effectiveness of randomized trials of acute disease.

Binomial Distribution↗
PubMed1988

Report from the panel on the Case for Registers of Clinical Trials at the Eighth Annual Meeting of the Society for Clinical Trials.

A plenary session at the Eighth Annual Meeting of the Society for Clinical Trials addressed "The Case for Registers of Clinical Trials." There are a number of reasons for having registers of clinical trials: to promote collaboration and communication among investigators regarding new and ongoing clinical trials, to provide a basis for methodologic research, and to facilitate meta-analysis by the availability of a system of trial identification that is independent of the published literature. The experience gleaned by those involved with two existing trial registers, the International Committee on Thrombosis and Haemostasis Registry and the Oxford Database of Perinatal Trials, can be used to provide insight into the issues generic to trial registration. The time perspective to be used, inclusion and exclusion criteria, the practicability of comprehensive prospective registration, and funding are central considerations for these and other registers.

Clinical Trials as Topic↗
PubMed2026

Network-Integrated Platform for Clinical Trial Navigation from the New South Wales Early Phase Clinical Trials Alliance.

PURPOSE: Access to early-phase clinical trials (EPCT) is increasingly constrained by delays in genomic testing and lack of coordinated system-level navigation. The New South Wales Early Phase Clinical Trials Alliance (NECTA) was established to improve EPCT access. Practical Assessment of NECTA Network Assistance in Cancer Outpatient Trials Access (PANNA-COTA) prospectively evaluated whether integrating circulating tumor DNA (ctDNA) profiling with a real-time, cross-site molecular tumor board (MTB) facilitates EPCT enrollment. PATIENTS AND METHODS: In this multicenter prospective study across nine NECTA sites, patients referred for EPCT consideration underwent ctDNA testing using the Guardant360 74-gene assay. The results were reviewed at a fortnightly MTB incorporating cross-site trial mapping and dynamic eligibility review. The primary endpoint was proportion enrolled into EPCTs. Secondary endpoints included ctDNA findings and trial outcomes. RESULTS: Of 104 consented participants, 101 were eligible. Participants had advanced, heavily pretreated solid tumors; 48% lacked prior tumor next-generation sequencing. ctDNA alterations were detected in 85%, with actionable alterations in 44%. Therapeutic options were identified in 88%, and EPCTs were recommended in 76%. Despite this, only 7% of participants received genomically matched therapy. In contrast, 37% enrolled in EPCTs within 3 months and 47% overall [95% confidence interval (CI), 0.37-0.56]. Among evaluable participants on trial, the disease control rate was 81% and objective response rate was 33%. CONCLUSIONS: PANNA-COTA demonstrates that integrating liquid biopsy with real-time, network-level trial navigation enables high rates of EPCT enrollment despite low rates of genomically matched therapy. These findings indicate that clinical trial access is influenced by navigation, eligibility, and system-level coordination rather than genomic actionability alone.

Humans↗