Multifactor Intervention Research Articles

Testing homogeneity of the risk ratio in stratified noncompliance randomized trials

The risk ratio (RR), defined as the ratio of probabilities of having an adverse event between an experimental treatment and a control treatment, is one of the most commonly used indices to measure the efficacy of an experimental treatment in a randomized clinical trial (RCT). When we want to obtain a summary estimator of the RR in stratified analysis, it is important that we can examine the assumption whether the underlying RR varies between strata. Although we can find a few publications on testing the homogeneity of RR, all these papers focus the ideal situation in which every patient complies with his/her assigned treatment. The research on testing the homogeneity of RR for a noncompliance RCT is limited. In this paper, we develop three simple test statistics for testing homogeneity of the RR under a noncompliance stratified RCT with large strata. To evaluate the performance of these statistics, we apply Monte Carlo simulation to calculate Type I error and power in a variety of situations. Based on the findings, we provide a general guideline of selecting a preferable test statistic under various situations. Finally, we include a large field trial studying the effect of a multifactor intervention program on the mortality of coronary heart disease (CHD) in middle-aged men to illustrate the practical use of these test statistics.

Effect evaluation of a multifactor community intervention to reduce falls among older persons

The objective of the study was to evaluate the effectiveness of a multifactor and multi-method community intervention programme to reduce falls among older persons by at least 20%. In a pre-test – post test design, self-reported falls were registered for 10 months in the intervention community and two control communities. After the pre-test registration, participants followed the intervention programme (Information and education, Training and exercise and Environmental modifications) for 14 months. All communities were situated in the Province of Friesland in the north of The Netherlands. The study ran from November 1999 to November 2002. The participants (intervention 1122; control 630) were aged 65 years and older and lived independently. There was no significant decrease in total falls, except outside the home, among women (odds ratio = 0.54, 95% CI = 0.30 – 0.98; p = 0.041). The multifactor intervention programme was not effective. The reduction of falls outside the home among women could be due to reduced outdoor physical activity.

Addressing issues of asthma in inner-city children

For children living in the inner city, asthma tends to be more frequent and severe. Although the causes for this heightened severity of asthma are not clearly established, environmental allergens likely play a major role. To characterize, understand, and treat children with asthma living in the inner city better, the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health established an Inner City Asthma Program in 1991. Over the past 15 years, 3 separate inner-city asthma research networks have been formed and funded by this institute. The work from these programs has led to important observations including evidence that environmental allergens, particularly cockroach, are important for sensitization and severity of asthma of the affected children. Furthermore, reductions in the allergen load can lead to improved asthma control. The most recent program, the Inner City Asthma Consortium, was formed in 2002 with a goal to develop immune-based therapy for children with asthma in the inner city and to determine mechanisms of these therapies as well as immunopathogenesis of asthma in these high-risk children. This article reviews these programs and how they have begun the effort to understand and treat children with asthma who live in inner cities better and what their findings mean in relationship to unique features of asthma in inner city children.

Evidence-based patient handling: systematic review.

This article summarises the findings of an international systematic review of patient handling. More than 880 papers were read, critically appraised and allocated a quality rating score. The evidence supports the provision of a minimal set of equipment for moving and handling patients, and multifactor intervention strategies based on risk assessment rather than those predominantly based on technique training. It is recommended that healthcare providers should review their current equipment provision and approach to managing risks and injuries associated with patient handling activities in the context of this research evidence.

On the Effect of Treatment among Would-Be Treatment Compliers: An Analysis of the Multiple Risk Factor Intervention Trial

Abstract The Multiple Risk Factor Intervention Trial (MRFIT) was a major trial that examined the efficacy of a multifactor intervention on reducing coronary heart disease mortality. After a mean follow-up of 7 years, treatment was not significantly different from control, and extensive investigation was undertaken to explain the result. This article examines how the effect of treatment varies with compliance with treatment. The basic idea is that the binary characteristic “would comply with treatment” is balanced between groups by randomization, even though it is unobservable before randomization and only observed after randomization in the treatment group. Using baseline covariates, a prediction model for this observed characteristic is developed in the treatment group, and estimated probabilities of treatment compliance are calculated for all patients in both groups. The assumption that patients who would not comply with treatment must have the same mean response in both groups is avoided. Two methods for examining how the effect of treatment depends on treatment compliance are described. Under the first approach, the predicted probabilities of treatment compliance are used to specify a treatment by covariate interaction. Under the second approach, a regression model is specified where the covariate “would comply with treatment” has an interaction with treatment. This produces a standard regression model in the treatment group and a mixture model with mixing over the unobserved binary covariate in the control group. The two methods are applied to MRFIT and the results compared.

On the Effect of Treatment among Would-Be Treatment Compliers: An Analysis of the Multiple Risk Factor Intervention Trial

The Multiple Risk Factor Intervention Trial (MRFIT) was a major trial that examined the efficacy of a multifactor intervention on reducing coronary heart disease mortality. After a mean follow-up of 7 years, treatment was not significantly different from control, and extensive investigation was undertaken to explain the result. This article examines how the effect of treatment varies with compliance with treatment. The basic idea is that the binary characteristic “would comply with treatment” is balanced between groups by randomization, even though it is unobservable before randomization and only observed after randomization in the treatment group. Using baseline covariates, a prediction model for this observed characteristic is developed in the treatment group, and estimated probabilities of treatment compliance are calculated for all patients in both groups. The assumption that patients who would not comply with treatment must have the same mean response in both groups is avoided. Two methods for examining how the effect of treatment depends on treatment compliance are described. Under the first approach, the predicted probabilities of treatment compliance are used to specify a treatment by covariate interaction. Under the second approach, a regression model is specified where the covariate “would comply with treatment” has an interaction with treatment. This produces a standard regression model in the treatment group and a mixture model with mixing over the unobserved binary covariate in the control group. The two methods are applied to MRFIT and the results compared.

The Multiple Risk Factor Intervention Trial (MRFIT)<subtitle>A Return to a Landmark Trial</subtitle>

In 1982 the results of the landmark Multiple Risk Factor Intervention Trial (MRFIT) were published in JAMA . 1 MRFIT was a randomized primary prevention trial funded by the National Heart and Lung Institute (now the National Heart, Lung, and Blood Institute) to test whether multifactor intervention in 12 866 high-risk, asymptomatic middle-aged men would prevent fatal coronary heart disease (CHD) events compared with usual care. Minimum follow-up was 6 years. MRFIT grew from the Task Force on Arteriosclerosis convened in 1970 by the National Heart and Lung Institute to devise a long-range strategy for preventing, treating, and controlling arteriosclerosis and its complications. 2 The task force thoroughly reviewed data that had come from epidemiologic observations in the United States and abroad—including the findings of the Framingham Heart Study, the Seven Countries Study, and the Chicago Workers Study—and from clinical observations and smaller clinical trials linking risk factor modification

Multiple Risk Factor Intervention Trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group. 1982

The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC). Over an average follow-up period of seven years, risk factor levels declined in both groups, but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically nonsignificant difference of 7.1% (90% confidence interval, -15% to 25). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others.

Multifactor behavioral treatment of chronic sleep-onset insomnia using stimulus control and the relaxation response. A preliminary study.

Sleep latency changes following behavioral interventions for sleep-onset insomnia are only moderate because the majority of insomniacs do not achieve good sleeper status at posttreatment. This study evaluated the efficacy of a multifactor behavior intervention consisting of stimulus control and relaxation-response training (n = 10) compared to stimulus control alone (n = 10) for sleep-onset insomnia. Only the multifactor subjects' mean posttest sleep latency fell within the good sleeper range. They also exhibited a 77% improvement on mean sleep-onset latency compared to the stimulus control group (63%). Thus a multifactor intervention may be more effective than stimulus control alone for treatment of sleep-onset insomnia.

Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial.

The Multiple Risk Factor Intervention Trial (MRFIT) is a randomized primary prevention trial that tested the effect of a multifactor intervention program on coronary heart disease (CHD) mortality in 12,866 high-risk men aged 35-57 years. Men were randomly assigned to either a special intervention (SI) program, which consisted of dietary advice for lowering blood cholesterol levels, counseling aimed at cessation for cigarette smokers, and stepped-care treatment for hypertension for those with elevated blood pressure, or to their usual sources of health care within the community (UC). Among the 12,866 randomized men, 8,012 (62%) were hypertensive at baseline. For this subgroup, mortality rates with 10.5 years of follow-up were lower for the SI than for the UC group by 15% (p = 0.19) for CHD and 11% (p = 0.13) for all causes. These results reflected more favorable outcomes for SI compared with UC hypertensive men during the 3.8 posttrial years (March 1982 through December 1985) than during the preceding 6-8 years (through February 1982). During the posttrial years, death rates were lower for SI than for UC men by 26% (p = 0.09) for CHD and 23% (p = 0.02) for all causes. For those with diastolic blood pressure equal to or more than 100 mm Hg, this posttrial trend was a continuation of a trend during the trial; therefore, with 10.5 years of follow-up, death rates were markedly lower for SI than for UC by 36% (p = 0.07) for CHD and 50% (p = 0.0001) for all causes. Similarly, for those without baseline resting electrocardiographic abnormalities, the favorable posttrial outcome for the SI group was a continuation of a trend during the trial. In contrast, for those with baseline diastolic blood pressure of 90-99 mm Hg and for those with baseline resting electrocardiographic abnormalities, the favorable posttrial mortality findings for the SI group were a reversal of unfavorable trends recorded during the trial. Two factors appear to have contributed to this more favorable mortality trend for the SI group: 1) a change in the diuretic treatment protocol for SI men about 5 years after randomization, which involved replacement of hydrochlorothiazide with chlorthalidone at a daily maximum dose of 50 mg; and 2) a favorable effect of intervention on nonfatal cardiovascular events during the trial years. In addition, delay until the full impact of beneficial effects on mortality end points from smoking cessation and cholesterol lowering could have contributed.(ABSTRACT TRUNCATED AT 400 WORDS)

Recruitment of participants for the Multiple Risk Factor Intervention Trial (MRFIT)

The Multiple Risk Factor Intervention Trial (MRFIT) was a randomized primary prevention trial designed to test the effect of multifactor intervention on mortality from coronary heart disease. Before randomization, men were seen at three screening visits to establish eligibility. A total of 361,662 men were screened, and 12,866 men were randomized, 866 more than the goal of 12,000. The total time required for planning and recruitment was 44 months. Eligibility rates and dropout or refusal rates between screening visits varied considerably among the 20 clinics that took part in MRFIT. The variation in eligibility rates resulted largely from subjective interpretation by the staff of the willingness of the men to participate in the study and to make risk factor changes. Cigarette smokers and blacks were more likely to discontinue their participation between screening exams. The ultimate success of the MRFIT recruitment is attributed to (1) the previous experience of investigators in screening large numbers of participants for clinical trials and similar epidemiologic investigations, (2) the identification at each clinic of one or more persons whose specific responsibility was recruitment, (3) the phased entry of clinics into the study, (4) routine monitoring and reporting of recruitment rates by the coordinating center, (5) regular discussion of recruitment successes and problems at the Steering Committee meetings, and (6) site visits to examine in detail recruitment problems.

Plasma High-Density Lipoprotein Cholesterol Level

Determinants of circulating high density lipoproteins (HDL) were sought in 301 men studied during a year of participation in a coronary prevention program. Mean plasma HDL-cholesterol concentration rose by 2.8 mg/dl (6%) in the group receiving multifactor intervention, but the change did not differ significantly from that in the comparison group. Larger changes in both directions were seen in many individuals. Multiple regression analysis of these changes indicates that increased plasma HDL levels occur when plasma triglyceride level is decreased, cigarette smoking is reduced, and habitual alcohol intake is increased. Increases in the concentration of HDL-cholesterol also tended to accompany adherence to the fat-controlled diet, reduction in LDL-cholesterol level, and loss of body weight. Conventional coronary prevention programs are unlikely to have an adverse influence on this new, risk-lowering factor.