Analysis of combined data from heterogeneous study designs: an applied example from the patient navigation research program.

Background: The Patient Navigation Research Program (PNRP) is a cooperative effort of nine research projects, with similar clinical criteria but with different study designs. To evaluate projects such as PNRP, it is desirable to perform a pooled analysis to increase power relative to the individual projects. There is no agreed-upon prospective methodology, however, for analyzing combined data arising from different study designs.

Celecoxib for the prevention of sporadic colorectal adenomas.

Background: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia.

Methods: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin.

The fallacy of enrolling only high-risk subjects in cancer prevention trials: is there a "free lunch"?

Background: There is a common belief that most cancer prevention trials should be restricted to high-risk subjects in order to increase statistical power. This strategy is appropriate if the ultimate target population is subjects at the same high-risk. However if the target population is the general population, three assumptions may underlie the decision to enroll high-risk subject instead of average-risk subjects from the general population: higher statistical power for the same sample size, lower costs for the same power and type I error, and a correct ratio of benefits to harms.

Non-steroidal anti-inflammatory drug use is associated with reduction in recurrence of advanced and non-advanced colorectal adenomas (United States).

Objective: To prospectively examine the association between non-steroidal anti-inflammatory drugs (NSAIDs) use (including dose and dosage schedule) and the recurrence of colorectal adenomas among individuals who were diagnosed with an adenoma at entry into a clinical trial.

Methods: For this analysis, participants who completed the full follow-up (n = 1905) for the Polyp Prevention Trial (PPT) were evaluated. Information on current use and dose of NSAIDs and other drugs was obtained at baseline and at each subsequent study visit over the duration of the trial.

Lack of effect of a low-fat, high-fruit, -vegetable, and -fiber diet on serum prostate-specific antigen of men without prostate cancer: results from a randomized trial.

Purpose: To determine whether a diet low in fat and high in fruits, vegetables, and fiber may be protective against prostate cancer by having an impact on serial levels of serum prostate-specific antigen (PSA).

Methods: Six hundred eighty-nine men were randomized to the intervention arm and 661 to the control arm. The intervention group received intensive counseling to consume a diet low in fat and high in fiber, fruits, and vegetables.

Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial.

Background: The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ), high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat) diet on the recurrence of adenomatous polyps in the large bowel.

Self-rated quality of life measures: effect of change to a low-fat, high-fiber, fruit and vegetable enriched diet.

The Polyp Prevention Trial (PPT) was a multicenter, randomized clinical trial to determine the effect of a low-fat (20% of energy from fat), high-fiber (18 g/1,000 kcal/day), high-fruit/vegetable (3.5 servings/1,000 kcal/day) eatingplan on the recurrence of large bowel adenomatous polyps. The PPT provided an opportunity to examine the impact of dietary changes on quality of life.

Serum hormones and the alcohol-breast cancer association in postmenopausal women.

Background: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study.

Measuring cell proliferation in the rectal mucosa. comparing bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) assays.

Cell proliferation in the human colorectum can be measured using bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA) assays. Using data from the National Cancer Institute's Polyp Prevention Trial, these two assays are compared using correlation coefficients and variance components analysis. Adjusting for fixed as well as for the random effects of between-biopsy and scoring variation, the estimated correlation is 0.

Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group.

Background: We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers.

Methods: We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet.

Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? The Polyp Prevention Trial.

Background & Aims: The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas.

Methods: We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial.

An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial: can we detect informative differences among individuals' proliferation measures amid the noise?

We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U. S. National Cancer Institute's multicenter Polyp Prevention Trial.

A Voluntary Smokers' Registry: Characteristics of joiners and non-joiners in the Community Intervention Trial for Smoking Cessation (COMMIT).

Objectives: This paper examines differences between joiners and nonjoiners of a voluntary smokers' registry.

Methods: A baseline prevalence survey was used to identify characteristics of smokers who joined or did not join a smokers' registry.

Results: Communities varied significantly in registry enrollment rates.

Community Intervention Trial for Smoking Cessation (COMMIT): changes in community attitudes toward cigarette smoking.

The success of the Community Intervention Trial for Smoking Cessation (COMMIT) in changing smoking attitudes is examined by testing two primary hypotheses: (1) the priority of smoking as a public health problem increased more in the intervention communities than in the comparison communities, and (2) norms and values that support non-smoking increased more in the intervention than in the comparison communities. One community within each of 11 matched pairs was randomly assigned to receive a 4-year (1989-92) community-based smoking control intervention. Community attitudes towards smoking were measured primarily by cross-sectional surveys in 1989 (n = 9875) and 1993 (n = 14117) but a cohort (n = 5450) also provided attitude information.

Effect of proxy-reported smoking status on population estimates of smoking prevalence.

The use of proxy respondents in surveys designed to provide population estimates of smoking prevalence offers an inexpensive way to obtain these data. The accuracy of this information is examined in analyzing data from tobacco use surveys of adults conducted in 22 North American communities as part of the National Cancer Institute's Community Intervention Trial for Smoking Cessation. Proxy-reported smoking status was obtained in a cross-sectional telephone survey conducted from August 1993 to January 1994 (n = 99,682).

The efficiency of the matched-pairs design of the Community Intervention Trial for Smoking Cessation (COMMIT).

The Community Intervention Trial for Smoking Cessation (COMMIT) was a randomized trial to evaluate the effects of a community-wide smoking cessation intervention on smoking behavior. The statistical design involved 22 pair-matched communities and the randomization of one community in each of the 11 pairs to the intervention, with the other community in the pair acting as a comparison. Communities were matched on the basis of their geographical proximity and similarity of demographic composition.

The polyp prevention trial II: dietary intervention program and participant baseline dietary characteristics.

The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial to evaluate whether a low-fat, high-dietary fiber, high-fruit and -vegetable eating pattern will reduce the recurrence of adenomatous polyps of the large bowel. Men and women who had one or more adenomas removed recently were randomized into either the intervention (n = 1037) or control (n = 1042) arms. Food frequency questionnaire data indicate that PPT participants at the beginning of the trial consumed 36.

Interplay between design and analysis for behavioral intervention trials with community as the unit of randomization.

This paper outlines an approach for the design and analysis of randomized controlled trials investigating community-based interventions for behavioral change aimed at health promotion. The approach is illustrated using the Community Intervention Trial for Smoking Cessation (COMMIT), conducted from 1988 to 1993, involving 11 pairs of communities in North America, matched on geographic location, size, and sociodemographic factors. The situation discussed is when assignment to intervention is done at the community level; for COMMIT, the very nature of the intervention required this.

Smokers' baseline characteristics in the COMMIT trial.

Background: Baseline telephone survey data from 10 COMMIT sites were submitted to statistical analyses to compare the smoking characteristics of non-Hispanic white (white), non-Hispanic black (black), Mexican-origin (Mexican), and Puerto Rican-origin (Puerto Rican) smokers.

Results: White men and women were more likely to be classified as "heavy smokers" than members of other racial/ethnic groups, although black and Puerto Rican smokers were more likely than whites to increase their smoking rates on weekends. Whites were less likely to report stopping smoking in the past.

Radical prostatectomy versus expectant treatment for early carcinoma of the prostate. Twenty-three year follow-up of a prospective randomized study.

In a study by the Veterans Administration Cooperative Urological Research Group (VACURG), 142 patients with localized prostate cancer, VACURG stage I and II, were randomized between radical prostatectomy plus placebo versus placebo alone as initial treatment. 111 patients were evaluable for treatment comparison. Median follow-up for survival is 23 years.

Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates.

Data on patients with extrahepatic bile duct carcinomas recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. We analyzed the records of 1766 patients reported during a 10-year period (1977-1986). These tumors occurred primarily in older age groups and were slightly more common in males.

Carcinoma of the gallbladder. Histologic types, stage of disease, grade, and survival rates.

Data on patients with gallbladder cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. Between 1977 and 1986, 3038 patients were recorded in the Program. Histologic grade, histologic type, stage of disease, and vascular invasion were correlated with outcome.

Aspects of statistical design for the Community Intervention Trial for Smoking Cessation (COMMIT).

We present statistical considerations for the design of the Community Intervention Trial for Smoking Cessation (COMMIT). One outcome measurement, the quit rate in randomly selected cohorts of smokers, is compared with another outcome measurement, the decrease in smoking prevalence, in terms of statistical efficiency and interpretability. The COMMIT study uses both types of outcome measurements.

Radical prostatectomy versus expectant primary treatment in stages I and II prostatic cancer. A fifteen-year follow-up.

A fifteen-year follow-up of a prospective, randomized study comparing placebo with radical prostatectomy as the primary treatment of early prostatic cancer is presented. A total of 111 patients with clinical Stage I or II prostatic cancer, normal acid phosphatase levels, and negative findings on skeletal x-ray film were evaluable. Thirty Stage I patients and 20 Stage II patients received placebo only; 31 Stage I and 30 Stage II patients underwent radical prostatectomy.

Evaluation Plan for the Community Intervention Trial for Smoking Cessation (COMMIT).

The National Cancer Institute is sponsoring the Community Intervention Trial for Smoking Cessation (COMMIT), a multi-center research project designed to test the value of a community-based effort to promote smoking cessation. The trial involves eleven matched pairs of communities with random assignment of one community per pair to the intervention or to the comparison condition. This article reviews the rationale and methodology of the COMMIT evaluation plan which is organized into four components: 1) outcome assessment, monitoring changes in community smoking patterns; 2) impact assessment, measuring the effect of the COMMIT intervention on mediating factors thought to be important in facilitating changes in community smoking behavior (e.