Biomedical subjects

Patricia Grambsch

Publications and source records attributed to Patricia Grambsch.

7 recordsLinked to original sources

PubMed2006

Sample size calculation in survival trials accounting for time-varying relationship between noncompliance and risk of outcome event.

BACKGROUND: Most methods of sample size calculations for survival trials adjust the estimated outcome event rates for noncompliance based on the assumption that non-compliance is independent of the risk of the outcome event although there has been published evidence that noncompliers are often at a higher risk than compliers. More recent work has started to consider the situations of informative noncompliance and different risks for noncompliers. However, the possibility of a time-varying association between noncompliance and risk has been ignored. Our analysis indicated a strong time-varying relationship between noncompliance defined as permanent discontinuation of study treatments and risk of the outcome event in the CONVINCE trial. PURPOSE: The purpose of this research is to develop methods for the log-rank sample size calculations for two-arm clinical trials that allow for the relationship between risk and noncompliance to vary over time and to study how sample size requirements vary with different patterns of the time relationship. METHODS: The method developed takes Lakatos' Markov chain approach as a basis, modifying it to incorporate time dynamics, and emphasizing permanent discontinuation of study medication as the form of noncompliance to be considered. RESULTS: Results with our method show that sample size depends on the relative rates of noncompliance in the two arms, the hazard for the outcome event following non-compliance, whether it involves switching to the hazard of the opposite arm or is common to both arms, and whether noncompliance occurs early or late in the trial. These factors interact with each other in complex ways, precluding simple summaries. LIMITATIONS: This research focuses on two-arm clinical trials with time to event as primary outcome measure. The method developed is not directly applicable to trials with more complicated designs and/or trials with other types of primary outcome. CONCLUSIONS: The pattern of the relationship between noncompliance and risk can have a dramatic impact on the sample size and power calculations in survival studies. The method introduced provides a useful tool for investigators to explore the optimal sample size accounting for various dynamic associations between noncompliance and risk.

Clinical Trials as Topic↗

PubMed2005

Results of the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial by geographical region.

OBJECTIVE: To examine regional differences in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. DESIGN: Double-blind, randomized, international clinical trial. SETTING: Six hundred and sixty-one clinical centers in 15 countries. PATIENTS: Hypertensive volunteers (n = 16,602) with > or =1 additional cardiovascular risk factor, grouped into four regions: USA (n = 8144), Canada (n = 3405), Western Europe (Spain, UK, Italy, Sweden, Germany; n = 2048) or 'other' (Bulgaria, Israel, Mexico, Czech Republic, Hungary, Poland, Slovakia, Brazil; n = 2879); subgroupings included country and state/province within the USA and Canada. INTERVENTIONS: Randomized to COER-verapamil or the investigator's choice of either atenolol or hydrochlorothiazide, titrated and additional drugs added as required. MAIN OUTCOME MEASURES: Baseline characteristics; blood pressure control, medication adherence and lost-to-follow-up at 2 years; and composite primary endpoint (stroke, myocardial infarction, cardiovascular death) by regional groupings. RESULTS: Regional differences were found at baseline for age, gender, blood pressure, percentage receiving antihypertensive drug therapy, initial choice of atenolol or hydrochlorothiazide, and risk factor profile. Blood pressure control rates increased markedly during follow-up in all regions, but varied significantly by region. Blood pressure control, medication adherence and lost-to-follow-up rates were poorest in the USA. After adjustment for baseline differences, the primary-event rate for each region was significantly lower than for the USA. Although baseline factors, blood pressure control and event rates varied by region, treatment differences did not. CONCLUSION: Despite differences in baseline and follow-up measures across geographical regions, the absence of treatment differences by region suggests that the overall findings of CONVINCE are robust.

Aged↗

PubMed2004

Pulsatile luteinizing hormone disruption in depression.

Two independent groups recently published data comparing pulsatile luteinizing hormone (LH) release between depressed and control women. Despite similar populations and LH sampling frequency, they reached different conclusions: Meller et al. [Am. J. Psych. 154 (1997) 1454] found disruption of normal LH pulsatility in depressed women, whereas Young et al. [Arch. Gen. Psych. 57 (2000) 1157] did not. To resolve this discrepancy, the current study applies a single, well-established statistical method, spectral analysis, to the two data sets and concludes that both depressed populations display significantly altered LH pulsatile release.

Adult↗

PubMed2002

Periodograms and pulse detection methods for pulsatile hormone data.

Pulse detection algorithms and spectral analysis are the two most common methods for analysing pulsatile hormone data. We compared a popular high quality pulse detection algorithm (CLUSTER) to spectral analysis on a data set comparing luteinizing hormone data in depressed and control women. For these data, periodogram analysis methods, in particular Fisher's periodicity test, were superior in distinguishing the groups. Extending the pulse detection method to include measures of intra-individual variability improved its discriminatory performance. The two methods complement each other.

Adult↗

PubMed2002

Fruits, vegetables, and adenomatous polyps: the Minnesota Cancer Prevention Research Unit case-control study.

Although high vegetable intakes have been associated with a lower risk of colorectal cancer, this relation is less well established for the precursor lesions, adenomatous polyps. With a case-control design involving adenomatous polyp cases (n = 564), colonoscopy-negative controls who were polyp free at colonoscopy (n = 682), and community controls (n = 535), this 1991-1994 Minnesota Cancer Prevention Research Unit study investigated the relation between fruit and vegetable consumption and first incident adenomatous polyps. Dietary intake was assessed using a food frequency questionnaire. For women, adenoma risk was approximately halved in the highest versus lowest quintile of juice consumption (cases vs. colonoscopy-negative controls: odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.27, 0.92; cases vs. community controls: OR = 0.56, 95% CI: 0.30, 1.06). The association was stronger for adenomas with moderate or severe dysplasia compared with mild dysplasia. Juice was not associated with adenoma risk in men. The results for fruits, vegetables, total fruits and vegetables, green leafy vegetables, and several botanically and phytochemically defined subgroups generally were not statistically significant. Because elevated vegetable consumption has been associated with a lower risk of colorectal cancer, vegetables may have a stronger role in preventing the progression of adenomas to carcinomas rather than in preventing the initial appearance of adenomas.

Adenomatous Polyps↗

PubMed2001

Baseline Characteristics and Early Blood Pressure Control in the CONVINCE Trial.

-Blood pressure (BP) control rates around the world are suboptimal. Part 2 of the National Health and Nutrition Educational Survey (NHANES) III indicates that only 27.4% of hypertensive Americans aged 18 to 74 years have a BP of <140/90 mm Hg. We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Study, an international clinical trial that compares outcomes in hypertensive patients randomized to initial treatment with either controlled-onset extended-release verapamil or the investigator's choice of atenolol or hydrochlorothiazide. At randomization, BP was <140/90 mm Hg in only 20.3% of the 16 602 subjects (average+/-SD age 65.6+/-7.4 years; 56% women, 84% white/7% black/7% Hispanic). The average BP at enrollment was 148/85 mm Hg for patients taking BP medications (n=13 879) and 161/94 mm Hg for previously untreated patients (n=2723). After medication titration, with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg, 84.8% of the subjects attained the goal BP. During 2 years of treatment, BP control was maintained in 67% to 69% of the subjects (69% to 71% for systolic BP of <140 mm Hg and 90% for diastolic BP of <90 mm Hg). These data suggest that the control of systolic BP is more difficult than the control of diastolic BP. The US national goal of having 50% of hypertensives with a BP of <140/90 mm Hg may be achievable if a forced titration strategy is used. Interested investigators, free care and medications, and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population.

Journal Article↗

PubMedDate not supplied

Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.

CONTEXT: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. OBJECTIVE: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. INTERVENTION: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. MAIN OUTCOME MEASURES: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. RESULTS: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P =.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n = 118) compared with the atenolol or hydrochlorothiazide group (n = 79) (HR, 1.54 [95% CI, 1.16-2.04]; P =.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). CONCLUSIONS: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.

Adrenergic beta-Antagonists↗