Biomedical subjects

Michael A Proschan

Publications and source records attributed to Michael A Proschan.

13 recordsLinked to original sources

PubMed2006

Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm.

Amlodipine↗

PubMed2006

Comparison of two or more measurement techniques to a standard.

With advancing medical technology come new and less invasive ways to measure the extent of a patient's disease. These techniques may be preferred to an invasive standard even if they are not quite as accurate. They may also be the only available tools because some patients are not sufficiently stable to be measured the standard way. The question then becomes, does one newer method more closely match the standard than another? For comparison of a single new method to a standard, one measures patients using each method and assesses the distribution of differences. But how does one compare the distributions of differences when there are multiple newer techniques? At least two components of these distributions are important. One is the mean difference or bias, but its absolute value is what is most relevant; a bias of -3 is better than a bias of +4. Another important component is the variance of the differences. If two methods have similar and small absolute bias, the one yielding a smaller variance of differences is preferred. We derive methods of comparing absolute biases, variances of errors, and parameters that combine biases and variances.

Bias↗

PubMed2006

Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial.

BACKGROUND: The main 6-month results from the PREMIER trial showed that comprehensive behavioral intervention programs improve lifestyle behaviors and lower blood pressure. OBJECTIVE: To compare the 18-month effects of 2 multicomponent behavioral interventions versus advice only on hypertension status, lifestyle changes, and blood pressure. DESIGN: Multicenter, 3-arm, randomized trial conducted from January 2000 through November 2002. SETTING: 4 clinical centers and a coordinating center. PATIENTS: 810 adult volunteers with prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm Hg; diastolic blood pressure, 80 to 95 mm Hg). INTERVENTIONS: A multicomponent behavioral intervention that implemented long-established recommendations ("established"); a multicomponent behavioral intervention that implemented the established recommendations plus the Dietary Approaches to Stop Hypertension (DASH) diet ("established plus DASH"); and advice only. MEASUREMENTS: Lifestyle variables and blood pressure status. Follow-up for blood pressure measurement at 18 months was 94%. RESULTS: Compared with advice only, both behavioral interventions statistically significantly reduced weight, fat intake, and sodium intake. The established plus DASH intervention also statistically significantly increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the advice only group, the odds ratios for hypertension at 18 months were 0.83 (95% CI, 0.67 to 1.04) for the established group and 0.77 (CI, 0.62 to 0.97) for the established plus DASH group. Although reductions in absolute blood pressure at 18 months were greater for participants in the established and the established plus DASH groups than for the advice only group, the differences were not statistically significant. LIMITATIONS: The exclusion criteria and the volunteer nature of this cohort may limit generalizability. Although blood pressure is a well-accepted risk factor for cardiovascular disease, the authors were not able to assess intervention effects on clinical cardiovascular events in this limited time and with this sample size. CONCLUSIONS: Over 18 months, persons with prehypertension and stage 1 hypertension can sustain multiple lifestyle modifications that improve control of blood pressure and could reduce the risk for chronic disease.

Adult↗

PubMed2006

Combining treatment selection and definitive testing.

This is a discussion of the following two papers appearing in this special issue on adaptive designs: 'An adaptive hierarchical test procedure for selecting safe and efficient treatments' by Franz König, Peter Bauer and Werner Brannath, and 'An adaptive two-stage design with treatment selection using the conditional error function approach' by Jixian Wang.

Clinical Trials as Topic↗

PubMed2006

Clinical trial results applied to management of the individual cancer patient.

The application of clinical trial results to the management of the individual cancer patient is not always straightforward. The results of a clinical trial indicate the "average" effect of an intervention, often expressed in terms of an absolute risk reduction, which is an estimate of the likelihood of benefit for a particular patient. However, within any clinical trial, there might be differences between groups of patients in underlying pathology, genetics, or biology, and some patients might benefit more from a new treatment than others. Thus, within a clinical trial, it might also be useful to group together patients with similar characteristics, and test for subgroup interaction. The test for interaction will indicate whether the magnitude of benefit differs from one prognostic subgroup to the next (a quantitative interaction). Much less common are qualitative interactions, in which a new treatment is beneficial in one subgroup but harmful in another. If the test for subgroup interaction is significant, then the effects of treatment may indeed differ between subgroups of patients, but this should be confirmed in other trials before a treatment is implemented in clinical practice.

Data Interpretation, Statistical↗

PubMed2005

Two-stage sample size re-estimation based on a nuisance parameter: a review.

Sample size calculations are important and difficult in clinical trails because they depend on the nuisance parameter and treatment effect. Recently, much attention has been focused on two-stage methods whereby the first stage constitutes an internal pilot study used to estimate parameters and revise the final sample size. This paper reviews two-stage methods based on estimation of nuisance parameters in either a continuous or dichotomous outcome setting.

Algorithms↗

PubMed2005

Adaptive regression.

Adjustment for prognostic covariates is recommended in clinical trials because relative to a t-test, it improves precision and adjusts for treatment imbalances caused by an "unlucky" randomization. But, inclusion of too many covariates can be counterproductive. In the quest to strike a balance between inclusion of all important variables and not going overboard, people have proposed methods such as stepwise regression, whereby the decision to include a covariate depends on post-randomization data. Covariate inclusion decisions are typically based on either the strength of its correlation with the outcome or the degree of treatment imbalance. Are these methods valid? Is there a valid way to analyze such data? These are some of the questions we address.

Algorithms↗

PubMed2005

Randomized trials of breast-conserving therapy versus mastectomy for primary breast cancer: a pooled analysis of updated results.

We have undertaken a pooled analysis of the 6 major randomized trials comparing mastectomy (MT) and breast-conserving therapy (BCT) in the treatment of primary breast cancer. Specifically, these trials compared the 2 most widely used options in local treatment: mastectomy and axillary dissection (MT) versus breast-conserving surgery, axillary dissection, and breast radiotherapy (BCT). The early results of these 6 trials formed the basis for a 1990 National Institutes of Health Consensus statement. However, most of these trials have recently published long-term follow-up results, and this pooled analysis incorporates the updated results of these 6 trials. For each of these trials, the observed number of treatment events was compared with that expected under the null hypothesis, given the number of patients per arm and the total number of events. Approximate odds ratios were computed using the observed and expected number of events, and the variance of the observed number of events. These were then pooled across trials to give overall odds ratios for the risk of locoregional recurrence, total recurrence, and death. Four of the 6 trials show that MT significantly reduces the risk of locoregional recurrence when compared with BCT, and the pooled odds ratio also shows a significant benefit for MT (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.289-1.890; P < 0.001). However, only 1 trial shows a statistically significant benefit for MT in reducing mortality, and the pooled odds ratio shows no significant difference between MT and BCT (OR, 1.070; 95% CI, 0.935-1.224; P = 0.33). This pooled analysis confirms that MT and BCT have comparable effects on mortality, even after long-term follow up. However, BCT is associated with a significantly greater risk of locoregional recurrence.

Adult↗

PubMed2004

Effect of the dietary approaches to stop hypertension diet and reduced sodium intake on blood pressure control.

The authors hypothesized that the Dietary Approaches to Stop Hypertension (DASH) diet and reduced sodium intake would control stage 1 hypertension and reduce high-normal blood pressure (BP) to optimal levels. Adults with systolic BP 120-159 mm Hg and diastolic BP 80-95 mm Hg were randomly assigned to receive the DASH diet or a typical American (control) diet, consuming three different sodium intakes (higher=142 mmol/d, intermediate=107 mmol/d, and lower=65 mmol/d) for 30 days each. BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Among subjects with hypertension at baseline, at higher sodium intake the DASH diet increased BP control two-fold over control (63% vs. 32%; 95% confidence interval, 1.4-2.9). Reducing sodium intake in the control diet group increased BP control 2.3-fold (74% vs. 32%; 95% confidence interval, 1.7-3.2). The maximum BP control rate (84%) was achieved with the DASH/lower sodium diet. BP became normal or optimal in 71% of persons consuming the control/lower sodium diet and 77% of persons consuming the DASH/lower sodium diet. Both the DASH diet and reduced sodium intake improved BP control.

Adult↗

PubMed2003

Individual blood pressure responses to changes in salt intake: results from the DASH-Sodium trial.

Although group characteristics are known to influence average blood pressure response to changes in salt intake, predictability of individual responses is less clear. We examined variability and consistency of individual systolic blood pressure responses to changes in salt intake in 188 participants who ate the same diet at higher, medium, and lower (140, 104, 62 mmol/d) sodium levels for 30 days each, in random order, after 2 weeks of run-in at the higher sodium level. Regarding variability in systolic blood pressure changes over time, changes from run-in to higher sodium (no sodium level change) ranged from -24 to +25 mm Hg; 8.0% of participants decreased > or =10 mm Hg. Regarding variability in systolic blood pressure response to change in sodium intake, with higher versus lower sodium levels (78-mmol sodium difference), the range of systolic blood pressure change was -32 to +17 mm Hg; 33.5% decreased > or =10 mm Hg. Regarding consistency of response, systolic blood pressure change with run-in versus lower sodium was modestly correlated with systolic blood pressure change with higher versus medium sodium; systolic blood pressure change with higher versus lower sodium was similarly correlated with run-in versus medium sodium (combined Spearman r=0.27, P=0.002). These results show low-order consistency of response and confirm that identifying individuals as sodium responders is difficult. They support current recommendations for lower salt intake directed at the general public rather than "susceptible" individuals as one of several strategies to prevent and control adverse blood pressures widely prevalent in the adult population.

Adult↗

PubMed2003

Practical midcourse sample size modification in clinical trials.

Power calculations are very important in the planning of a well-designed clinical trial. Sometimes there is limited information available before the trial, making it highly desirable to adjust the sample size after seeing actual trial data. Indeed, there has been a recent proliferation of papers promising great flexibility in midcourse correction of sample size and other design features, such as choice of primary endpoint. We point out the difficulty in accurately estimating the treatment effect midway through a trial, and we encourage the use of a simple, conservative approach whereby sample size can be increased but not decreased from what was originally planned. We show how to compute the p value and confidence interval for this two-stage procedure. If the original sample size is maintained, analysis of the data is the same as for a fixed sample procedure.

Bayes Theorem↗

PubMed2003

Premier: a clinical trial of comprehensive lifestyle modification for blood pressure control: rationale, design and baseline characteristics.

PURPOSE: To describe PREMIER, a randomized trial to determine the effects of multi-component lifestyle interventions on blood pressure (BP). METHODS: Participants with above optimal BP through stage 1 hypertension were randomized to: 1) a behavioral lifestyle (BLS) intervention that implements established recommendations, 2) a BLS intervention that implements established recommendations plus the DASH diet, or 3) an advice only standard of care group. The two BLS interventions consist of group and individual counseling sessions for 18 months. The primary outcome is systolic BP at 6 months. Additional outcomes include diastolic BP and homocysteine at 6 months; systolic and diastolic BP at 18 months; fasting lipids, glucose and insulin at 6 and 18 months; and effects in subgroup. CONCLUSION: Results from the PREMIER trial will provide scientific rationale for implementing multi-component behavioral lifestyle intervention programs to control BP and prevent CVD.

Blood Pressure↗

PubMed2003

Estimation of energy requirements in a controlled feeding trial.

BACKGROUND: Estimating energy requirements is a frequent task in clinical studies. OBJECTIVE: We examined weight patterns of participants enrolled in a clinical trial and evaluated factors that may affect weight stabilization. The Harris-Benedict equation and the FAO/WHO equation, used in conjunction with physical activity levels estimated with the 7-d Physical Activity Recall, were compared for estimating energy expenditure. DESIGN: This was a multicenter, randomized controlled feeding trial with participants of the Dietary Approaches to Stop Hypertension Trial. For 11 wk, the amount of food participants received was adjusted to maintain their body weights as close to their initial weights as possible. Change-point regression techniques were used to identify weight-stable periods. Factors related to achieving weight stabilization were examined with logistic regression. RESULTS: A stable weight was achieved by 86% of the 448 participants during the run-in period and by 78% during the intervention period. Energy intake averaged 11 +/- 2.4 MJ/d (2628 +/- 578 kcal/d), with most participants (n = 270) requiring 9-13 MJ/d (2100-3100 kcal/d). The difference between predicted and observed intakes was highest at high estimated energy intakes, mainly because of high and probably incorrect estimates of the activity factor. Participants with lower energy intakes tended to need less adjustment of their energy intakes to maintain a stable weight than did participants with higher energy intakes. CONCLUSIONS: Weight stabilization is not affected by diet composition, sex, race, age, or baseline weight. Either the Harris-Benedict equation or the FAO/WHO equation can be used to estimate energy needs. Activity factors > 1.7 often lead to overestimation of energy needs.

Adolescent↗