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At least 217 records · Page 12Linked to original sources
PubMed1993

Determinants of accrual of women to a large, multicenter clinical trials program of human immunodeficiency virus infection. The AIDS Clinical Trials Group.

To determine factors influencing the enrollment of women in a large multicenter human immunodeficiency virus (HIV) clinical trials program in the United States, we analyzed enrollment and demographic data of the AIDS Clinical Trials Group (ACTG) during the period 1987-90. Women comprised 6.7% of 11,909 ACTG participants enrolled in 1987-90. Women entering ACTG trials were significantly more likely to be white (48.5%) and less likely to have ever used i.v. drugs (22.6%) than U.S. women reported to have AIDS (26.5% were white; 51.0% had ever used i.v. drugs, p < 0.0001). In a multiple logistic regression model, specific attributes of individual trials did not influence enrollment of women with the exception that trials that targeted asymptomatic persons had greater enrollment of women. There was wide variation among research units in the percentage of women enrolled (1.0-37.5%), and evidence of significant regional variation in the ability of units to recruit available women. Units with female principal or coprincipal investigators had more than twice the percentage of female enrollment as units headed by men (10.8 vs. 5.3%, p < 0.001). Enrollment of women in a large HIV clinical trials program was low and appeared to be influenced more by demographic and geographic factors that attributes of specific trials. An apparent positive influence of female leadership on the enrollment of women warrants further study.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Adherence and its management in clinical trials: implications for arthritis treatment trials.

Adherence in clinical trials is a consistent problem regardless of the disease process or organ system under investigation. In this paper data and examples from clinical trials examining cardiovascular diseases are used as the basis for a review of various adherence principles. Issues reviewed include: the importance of adherence in clinical trials, an overall program for adherence in clinical trials, and specific issues in adherence from arthritis clinical trials. Special attention is given to a program for the prevention of reduced adherence for participants of a clinical trial as well as acute and chronic intervention plans for those with good adherence and those with reduced adherence in a clinical trial.

Arthritis↗
PubMed2007

Multivariable modelling for meta-epidemiological assessment of the association between trial quality and treatment effects estimated in randomized clinical trials.

Methodological deficiencies are known to affect the results of randomized trials. There are several components of trial quality, which, when inadequately attended to, may bias the treatment effect under study. The extent of this bias, so far only vaguely known, is currently being investigated by 'meta-epidemiological' re-analysis of data collected as part of systematic reviews. As inadequate quality components often co-occur, we maintain that the suspected biases must be evaluated simultaneously. Furthermore, the biases cannot safely be assumed to be homogeneous across systematic reviews. Therefore, a stable multivariable method that allows for heterogeneity is needed for assessing the 'bias coefficients'. We present two general statistical models for analysis of a study of 523 randomized trials from 48 meta-analyses in a random sample of Cochrane reviews: a logistic regression model uses the design of the trials as such to give estimates; a weighted regression model incorporates between-trial variation and thus gives wider confidence intervals, but is computationally lighter and can be used with trials of more general design. In both models, heterogeneity in the bias coefficients can be incorporated in two ways. A stratification approach pools the estimates from models estimated on subgroups of the data. We explore stratification by reviews and by broad trial types, the latter of which gives larger subgroups of the data, circumventing instabilities. A multilevel approach also avoids instabilities and addresses the more fundamental problem of interpretation of the pooled multivariable effect in the presence of heterogeneity.

Clinical Trials as Topic↗
PubMed1999

Challenges faced in recruiting patients from primary care practices into a physical activity intervention trial. Activity Counseling Trial Research Group.

BACKGROUND: Special challenges are encountered when clinical trial recruitment targets a physician practice-based population, as opposed to recruiting from the community. Since most published information about recruitment has focused on the latter group, summation of successful primary-care-based recruitment strategies could prove useful for future trials recruiting from this population. METHODS: The Activity Counseling Trial (ACT) is a multicenter, randomized clinical trial that evaluated approaches to primary care-based interventions to increase physical activity in sedentary adults 35-75 years of age. Fifty-four clinicians from eight practices recruited 874 participants from three U.S. sites. Recruitment challenges that related, in great part, to the primary care setting included: (1) focusing on patients from ACT physician practices who had regularly scheduled or intend-to-schedule appointments within the next year; (2) placing trial staff in the clinical offices for recruitment purposes; and (3) placing trial interventionists in the physicians' offices. Other challenges were related to recruitment of minorities and men. RESULTS: Patient mailing yielded 43.4% of all randomized participants, followed by office-based questionnaires (32.5%) and direct telephone contact (21.6%). Based on a retrospective cost-effective analysis (indirect costs excluded), the self-administered office-based questionnaire was the least costly strategy for one site ($14/randomized participant), followed by patient mailing at another site ($58). The direct telephone contact method utilized at one site serving primarily a minority population yielded a per randomized participant cost of $80. CONCLUSIONS: Recruitment of clinical trial participants from practice-based populations requires modification of the strategies used to recruit from the community. Multiple strategies should be employed, followed closely for their respective yields, and adapted as needed.

Adult↗
PubMed2006

Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials.

BACKGROUND: Dietary supplementation with folic acid and vitamin B12 lowers blood homocysteine concentrations by about 25% to 30% in populations without routine folic acid fortification of food and by about 10% to 15% in populations with such fortification. In observational studies, 25% lower homocysteine has been associated with about 10% less coronary heart disease (CHD) and about 20% less stroke. METHODS: We reviewed the design and statistical power of 12 randomized trials assessing the effects of lowering homocysteine with B-vitamin supplements on risk of cardiovascular disease. RESULTS: Seven of these trials are being conducted in populations without fortification (5 involving participants with prior CHD and 2 with prior stroke) and 5 in populations with fortification (2 with prior CHD, 2 with renal disease, and 1 with prior stroke). These trials may not involve sufficient number of vascular events or last long enough to have a good chance on their own to detect reliably plausible effects of homocysteine lowering on cardiovascular risk. But, taken together, these 12 trials involve about 52,000 participants: 32,000 with prior vascular disease in unfortified populations and 14,000 with vascular disease and 6000 with renal disease in fortified populations. Hence, a combined analysis of these trials should have adequate power to determine whether lowering homocysteine reduces the risk of cardiovascular events within just a few years. CONCLUSION: The strength of association of homocysteine with risk of cardiovascular disease may be weaker than had previously been believed. Extending the duration of treatment in these trials would allow any effects associated with prolonged differences in homocysteine concentrations to emerge. Establishing a prospective meta-analysis of the ongoing trials of homocysteine lowering should ensure that reliable information emerges about the effects of such interventions on cardiovascular disease outcomes.

Cardiovascular Diseases↗
PubMed2004

Widening eligibility to phase II trials: constant arcsine difference phase II trials.

This paper presents a method for undertaking Phase II trials in which not all patients are considered equally likely to respond to treatment. In ovarian cancer, for example, it has been shown that response is less likely in patients who have failed the previous treatment after only a short interval compared to those who have a protracted failure-free interval [Gynecol. Oncol. 36 (1990) 207]. The method is analogous to those used in phase III trials which estimate relative rather than absolute effects; a constant odds ratio, for example, encompasses multiple relationships between response rates. Phase II trials commonly test the null hypothesis H(0): P or=p(1), where the response rate p(1) is the minimum required level of efficacy and p(0) the highest level which would indicate that the treatment is of no further interest. This approach can be extended by using the arcsine transformation to allow p(0) and p(1) to vary between patients, thus for the ith patient p(0i)=(sin c(i))(2) and the efficacy level is set to p(1i)=(sin (c(i)+b))(2). The value of the arcsine parameter b therefore determines efficacy and the test for efficacy in the trial then becomes a test of the null hypothesis H(0): B or=b. The value of b is determined by considering representative values of p(0) and p(1) and setting b=(sin(-1) radical p(1)-sin(-1) radical p(0)); b is thus the constant arcsine difference (CAD) between p(0i) and p(1i). The variance of B is 1/4n, which is independent of P, trial designs are therefore independent of P, implying that all patients for whom this difference is identical can be entered into the same trial. This paper considers single-stage and two-stage CAD Phase II trials.

Antibiotics, Antineoplastic↗
PubMed1997

Amyotrophic lateral sclerosis: lessons in trial design from recent trials.

The recent history of clinical trials in ALS is marked by a great diversity in trial design. This has limited the comparability of the trial results, and has resulted in intense discussions about which parameters should or should not be evaluated when testing a new drug for ALS. This article discusses, without any claim to completeness, some aspects of trial design in relation to past, ongoing and future ALS trials, including: choice of endpoints, measurement of disease progression, assessment of quality of life, placebo-controlled trials, open-label trials, collaboration with the industry, and methods for investigating mechanisms of action of experimental drugs.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Intraclass correlation coefficients for cluster randomized trials in primary care: data from the MRC Trial of the Assessment and Management of Older People in the Community.

The cluster randomized trial, in which groups rather than individuals are allocated to different interventions, is an increasingly popular design. In cluster trials observations on individuals within the same cluster may be correlated, and this lack of independence must be taken into account when designing a new trial. We present intraclass correlation coefficients derived from the Medical Research Council Trial of the Assessment and Management of Older People in the Community. This is a UK-based randomized trial comparing different methods of multidimensional screening for people aged 75 years and over. One hundred six general practices and over 30,000 individuals are taking part. Estimates of the intraclass correlation coefficients were obtained using one-way analysis of variance. This is by far the broadest collection of intraclass correlation coefficients for older people at the level of the primary care clinic published to date. The intraclass correlation coefficients presented will be useful in calculating sample sizes for cluster randomized trials and surveys at the primary care clinic level. In conjunction with other papers presenting collections of intraclass correlation coefficients, this paper should help to improve the quality of cluster randomized trials and hence help lead to more reliable estimates of the effectiveness of health care interventions.

Activities of Daily Living↗
PubMed2000

A brief review of the current breast cancer prevention trials and proposals for future trials.

The available results from breast cancer chemoprevention trials are reviewed. Four trials using tamoxifen have been performed of which three have reported efficacy results. A fifth trial using raloxifene has also been published. The largest tamoxifen trial shows approximately a 50% reduction in breast cancer incidence in the short term, but the two smaller trials have not found any incidence reduction. Greater agreement exists for side-effects - thromboembolic disease and endometrial cancers are raised about 2 to 3-fold when tamoxifen is used for 5 years. The possible reasons for the discrepancy in breast cancer reduction are explored. A review of trial parameters does not clearly explain this difference, and a meta-analysis indicates that all results are compatible with a 42% reduction in short-term incidence. Several important questions remain about the clinical implication of this result, including the effect on mortality, the appropriate risk groups for chemoprevention and the long-term effects on incidence. Continued follow-up of these trials is crucial for resolving these issues.

Adult↗
PubMed1999

Randomised trials in ovarian cancer: trial design considerations.

Randomised clinical trials are considered the definitive source of evidence for guiding decisions in clinical practice. The concept of a clinical trial is based on sound scientific, ethical, and practical principles. The strength of evidence that an individual trial provides is assessed on the manner in which these principles are incorporated into the design and execution of the trial. Since the way these principles are incorporated into a trial is judgmental, the strength of evidence from an individual trial is a matter of degree. The purpose of this paper is to present some of the scientific, ethical and practical considerations surrounding the selection of endpoints and determination of sample size for trials in ovarian cancer.

Female↗
PubMed2006

Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures.

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.

Activities of Daily Living↗
PubMed2006

Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics.

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent.

Clinical Trials as Topic↗
PubMed2000

Use of a screen log to audit patient recruitment into multiple randomized trials in the intensive care unit. Canadian Critical Care Trials Group.

OBJECTIVE: To develop and evaluate a screen log for monitoring enrollment in multiple randomized clinical trials conducted in a single center. SETTING: University-affiliated 20-bed tertiary care medical-surgical intensive care unit (ICU). PATIENTS: Consecutive ICU patients admitted between April 1995 and March 1997. METHODS: We developed a screen log for multicentered studies conducted in our ICU. Using a multiple-project, unicenter perspective, we evaluated the screen log as a tool for monitoring eligibility and enrollment of patients in four multicentered randomized trials focused on stress ulcer prophylaxis, blood transfusion thresholds, immunotherapy for sepsis and mechanical ventilation strategies. RESULTS: The screen log was used as an instrument to monitor trial execution. We recorded all aspects of study enrollment and created a taxonomy of reasons for nonenrollment into each trial. We calculated enrollment efficiency rates and used these data to develop strategies to maximize accrual. The screen log became a communication tool that fostered research-oriented continuous quality improvement initiatives for the management of concurrently conducted randomized trials in our ICU. CONCLUSIONS: Intensivists participating in several clinical trials may be interested in monitoring and maximizing enrollment when conducting multiple studies and understanding the influence of each trial on enrollment into the others. The unicenter, multiple-project screen log is one tool that may help to achieve these goals.

Canada↗
PubMed2003

Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements.

OBJECTIVE: This meta-analysis aimed to determine whether ambulatory blood pressure monitoring (ABPM) results from double-blind, placebo-controlled (DBPC) and prospective, randomized, open-label, blinded-endpoint (PROBE) hypertension trials are statistically comparable. METHODS: Two DBPC and three PROBE parallel-group studies were selected from an angiotensin II receptor blocker clinical programme. These were fixed-dose studies involving similar mild to moderate hypertensive patient populations. All used SpaceLabs 90207 ABPM devices, and each comprised a 4-week placebo period and a 4-8-week treatment period. Data from patients receiving telmisartan 80 mg were used to compare the results of DBPC (126 patients) and PROBE (734 patients) trials. The analysis had approximately 87% power to show equivalence between the two design types in terms of ruling out differences of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. Office blood pressure was also compared. RESULTS: The change from baseline in mean 24-h ambulatory SBP was -12.2 mmHg in DBPC trials and -12.3 mmHg in PROBE trials, a rounded difference of 0.2 mmHg [95% confidence interval (CI): -1.8, 2.1]. The change from baseline in mean 24-h ambulatory DBP was -7.7 mmHg in DBPC trials versus -7.9 mmHg in PROBE trials, a difference of 0.2 mmHg (95% CI: -1.1, 1.5). Ambulatory pulse pressure results were identical. CONCLUSIONS: Thus, changes in mean 24-h ambulatory blood pressure from the DBPC and PROBE trials in this meta-analysis are statistically equivalent in terms of ruling out a difference of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. This supports the validity of the PROBE design in assessing antihypertensive efficacy based on blinded ABPM measurements.

Antihypertensive Agents↗
PubMed2001

A brief review of the International Breast Cancer Intervention Study (IBIS), the other current breast cancer prevention trials, and proposals for future trials.

The available results from breast cancer chemoprevention trials are reviewed. Four trials using tamoxifen have been performed, of which three have reported efficacy results. A fifth trial using raloxifene has also been published. The largest tamoxifen trial shows approximately a 50% reduction in breast cancer incidence in the short term, but the two smaller trials have not found any incidence reduction. Greater agreement exists for side effects: thromboembolic disease and endometrial cancers are raised about 2- to 3-fold when tamoxifen is used for 5 years. The possible reasons for the discrepancy in breast cancer reduction are explored. A review of trial parameters does not clearly explain this difference, and a metanalysis indicates that all results are compatible with a 42% reduction in short-term incidence. Several important questions remain about the clinical implication of this result, including the effect on mortality, the appropriate risk groups for chemoprevention, and the long-term effects on incidence. Continued follow-up of these trials is crucial for resolving these issues.

Adult↗
PubMed2006

Formative research in clinical trial development: attitudes of patients with arthritis in enhancing prevention trials.

In preparation for randomised controlled trials (RCTs) of disease-modifying antirheumatic drugs in patients with early inflammatory arthritis (EIA), formative research was conducted to enhance the design of such trials. The objectives of this research were to (1) determine patients' educational needs as they relate to the necessary elements of informed consent; and (2) assess patients' interest in enrolling in a hypothetical prevention trial. In-depth interviews were conducted with nine patients. Seven patients were women and all but one white. The mean age was 48 years. During the 4-month enrolment period, only three patients with EIA were identified; six patients with longer duration of symptoms were also interviewed. Most patients were able to express the primary aim of a hypothetical prevention trial presented. Factors cited by patients favouring enrolment were potential for direct medical benefit and knowledge that they would be withdrawn from the trial if they developed symptoms. Factors cited by patients against enrolment were the inclusion of a placebo and general uncertainty regarding treatment required by the RCT design. Pending larger-scale empirical projects to explore patients' attitudes about prevention trials, small-scale formative research in advance of such trials ought to be conducted.

Adult↗
PubMed2003

Evidence for risk of bias in cluster randomised trials: review of recent trials published in three general medical journals.

OBJECTIVE: To examine the prevalence of a risk of bias associated with the design and conduct of cluster randomised controlled trials among a sample of recently published studies. DESIGN: Retrospective review of cluster randomised trials published in the BMJ, Lancet, and New England Journal of Medicine from January 1997 to October 2002. MAIN OUTCOME MEASURES: Prevalence of secure randomisation of clusters, identification of participants before randomisation (to avoid foreknowledge of allocation), differential recruitment between treatment arms, differential application of inclusion and exclusion criteria, and differential attrition. RESULTS: Of the 36 trials identified, 24 were published in the BMJ,11 in the Lancet, and a single trial in the New England Journal of Medicine. At the cluster level, 15 (42%) trials provided evidence for secure allocation and 25 (69%) used stratified allocation. Few trials showed evidence of imbalance at the cluster level. However, some evidence of susceptibility to risk of bias at the individual level existed in 14 (39%) studies. CONCLUSIONS: Some recently published cluster randomised trials may not have taken adequate precautions to guard against threats to the internal validity of their design.

Bias↗
PubMed2004

Randomisation in trials: do potential trial participants understand it and find it acceptable?

OBJECTIVE: To examine lay persons' ability to identify methods of random allocation and their acceptability of using methods of random allocation in a clinical trial context. DESIGN: Leaflets containing hypothetical medical, non-medical, and clinical trial scenarios involving random allocation, using material from guidelines for trial information leaflets. SETTING AND PARTICIPANTS: Adults attending further education colleges (n = 130), covering a wide range of ages, occupations, and levels of education. MAIN MEASURES: Judgements of whether each of five methods of allocation to two groups was random in a medical or non-medical scenario. Judgements of whether these allocation methods were acceptable in a randomised clinical trial scenario, with or without a scientific justification for randomisation. RESULTS: The majority of our group of participants judged correctly that allowing people their preference was not random, and that the following were random: using a computer with no information about the individual (recommended wording for MREC trial leaflets), tossing a coin, drawing a name out of a hat. Judgements were split over allocating people in turn (not a random allocation method but shares features with randomisation). Judgements were no different in medical and non-medical scenarios. Few of the correctly identified random methods were judged to be acceptable in a clinical trial scenario. Inclusion of a scientific justification for randomising significantly increased the acceptability of only one random method: allocation by computer. CONCLUSIONS: Current UK guidelines' recommended description of random allocation by computer seems warranted. However, while potential trial participants may understand what random allocation means, they may find it unacceptable unless offered an acceptable justification for its use.

Adolescent↗