Susan Tonascia

Content of reports on clinical trials: a critical review.

A 10% sample of English language papers, published in 1980, listed in Index Medicus, and classified under the heading, Clinical Trials, was used to assess the state of trials and reports from them. Tabulations are presented concerning the design of the trials represented by the papers in the sample. The manuscript concludes with a discussion of reporting responsibilities for investigators involved in trials and of methods for meeting those responsibilities.

Three-area epidemiological study of geographic differences in stroke mortality. II. Results.

An epidemiological study was conducted of geographic differences in stroke mortality between the following areas within the United States; Savannah, Georgia (high stroke rates), Hagerstown, Maryland (intermediate stroke rates) and Pueblo, Colorado (low stroke rates). Population samples 35--54 years of age of the three cities were drawn for interview and examination to determine medical conditions and living habits of these populations. The population samples were compared with emphasis on possible risk factors for stroke: serum cholesterol and glucose tolerance test determinations, weight and height measurements, blood pressure and cigarette smoking. The gradient of increasing prevalence of stroke-related risk factors from low to intermediate to high for the three cities was present for blood pressure in black females and white males and for glucose tolerance tests in whites and nonwhites. No other consistent pattern of increasing prevalence of risk factors for stroke was evident.

A follow-up study of the commission on chronic illness morbidity survey in baltimore —IV. Factors influencing mortality from stroke and arteriosclerotic heart disease (1954–1967)☆

Abstract The Commission on Chronic Illness Survey population has been followed from 1954 to 1967. Previous reports have described subsequent mortality in relation to demographic characteristics and population mobility to 1962. A recent study compared the survivorship of screenees and non-screenees. The present study extends the mortality follow-up to 1966–1967. Only 3.9 per cent of the population was lost to follow-up. Men had substantially higher all cause and arteriosclerotic heart disease mortality than women and blacks had higher all cause and stroke mortality than whites. A history of hypertension, heart disease, or diabetes was associated with a substantially increased risk of all cause, stroke and arteriosclerotic heart disease deaths. Individuals with abnormal screening tests also had a markedly increased mortality. A study of the married couples in the sample failed to reveal any evidence of spouse aggregation of either all cause or specific cause mortality.

Treatment effects monitoring committees and early stopping in large clinical trials

Background Treatment effects monitoring is a process carried out over the course of a trial to determine whether it should continue unaltered. The purpose of monitoring is to protect persons enrolled from harm, caused either by exposure to an ineffective or harmful treatment or failure to provide a better treatment. The aim of this paper is to characterize treatment effects monitoring committees (TEMCs) as extant in published trials and to examine the effect of their presence on the premature stopping of a trial. Methods Trials published in 1990–1995 in the Annals of Internal Medicine, Archives of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, New England Journal of Medicine or Controlled Clinical Trials were identi”ed via MEDLINE (4279 publications). Abstracts were screened to include only trials with parallel treatment designs and sample sizes of ¶200, reducing the set to 661 papers. Those papers were then read, reducing the set to 562 after exclusion of papers not reporting trial results. The results that follow come from a review of these 562 published papers and from the responses to two questionnaires. The ”rst was mailed to the corresponding author, and the second to the chair of the monitoring body or other contact as provided by the author in response to the ”rst questionnaire. Results Less than half (48%) of the 562 trials had TEMCs. Factors having a positive univariate relationship with the presence of a TEMC include National Institutes of Health (NIH) sponsorship, larger sample size, multicentered, longer data collection and follow-up, and mortality as an outcome. Most of the early stops occurred in trials with TEMCs (66 out of 78). The odds ratios for early stopping for trials with TEMCs versus those without TEMCs was 4.4 (CI: 2.3–8.5). Conclusions The evidence suggests that early stopping is associated with the presence of a TEMC, but a substantial number of trial reports do not mention the presence of a TEMC even when one was used to stop a trial early.

Treatment in the Hypertension Prevention Trial

The Hypertension Prevention Trial (HPT) was a randomized, controlled, multicenter (four clinics, four resource centers) trial designed to test the feasibility of achieving and sustaining dietary changes in the intake of calories, sodium, and potassium and to assess the effect of those changes on blood pressure in a normotensive population. The trial involved 841 men and women (plus a test cohort of 78) who, at the first baseline (BL) examination were in the age range of 25-49 years and had diastolic blood pressure (DBP) greater than or equal to 76 but less than 100 mm Hg (average of two readings), and at the examination prior to randomization (BL 2), had DBP greater than or equal to 78 but less than 90 mm Hg (also averaged). Participants were randomly assigned to a control treatment group (no dietary counseling) or to one of four dietary treatment groups involving counseling designed to reduce calorie intake, reduce sodium intake, reduce sodium and calorie intake, and reduce sodium and increase potassium intake. This chapter describes the process of recruiting participants for the trial. Methods used to identify and contact study participants are presented. Details of the steps involved in the recruitment process and strategies for reducing costs are discussed.Abstract The Hypertension Prevention Trial (HPT) was a randomized, controlled, multicenter (four clinics, four resource centers) trial designed to test the feasibility of achieving and sustaining dietary changes in the intake of calories, sodium, and potassium and to assess the effect of those changes on blood pressure in a normotensive population. The trial involved 841 men and women (plus a test cohort of 78) who, at the first baseline (BL) examination were in the age range of 25–49 years and had diastolic blood pressure (DBP) ≥ 76 but This chapter describes the counseling methods employed to help participants achieve the desired dietary changes. Counseling was provided to groups by trained interventionists and included instruction in food selection, food preparation, and behavior management skills. Counseling groups met weekly for the first 10 weeks of the trial, twice the following month, and bimonthly thereafter. Techniques used in the counseling program included group discussions, instructions for dietary record keeping, goal setting, individual diet analysis for each participant, cooking demonstrations, and taste testing of new foods.

A Population Survey of Symptoms Suggestive of Transient Ischemic Attacks

A sample of the Baltimore population was interviewed in order to determine the frequency of symptoms suggestive of transient cerebral ischemic attacks. Respondents were interviewed in their homes. A history of ten symptoms which may have occurred within the past two years was elicited. Of the 6,830 individuals that were interviewed, 52% had no symptoms and approximately 10% had three or more symptoms. The frequency of symptoms did not increase substantially with advancing age between ages 45 to 74 or very markedly by sex and race. Individuals reporting a history of cardiovascular disease, stroke or diabetes had a substantially higher frequency of symptoms. Also the frequency of symptoms appeared to be higher in the less-educated groups.

Three-area epidemiological study of geographic differences in stroke mortality. I. Background and methods.

An epidemiological study was conducted to determine the geographical variations in stroke mortality among three U.S. areas. They were Savannah, Georgia (high stroke rates), Hagerstown, Maryland (intermediate stroke rates) and Pueblo, Colorado (low stroke rates). In each area samples were drawn of the population in the 35--54 age group. The subjects were interviewed and examined to obtain the information required on medical conditions and/or living habits which would characterize each area. A brief medical and family history, as well as demographic and personal data, were obtained by interview. The medical examination included blood pressure, ECG, blood and urine chemistry, height and weight. In all three cities the response rate in the final sample selected was 90% (2,375 individuals) interviewed and 74% (1.939 individuals) examined.

FDA censoring of manufacturers' postmarketing commitments in HIV/AIDS drug approval letters

Context: Changing evidentiary standards and partial shift of the investigational phase of drug approval process to the postmarketing phase. Objective: To determine the availability of information for independent researchers needed to examine accelerated drug approvals to determine how they differ from traditional drug approvals in the HIV/AIDS domain. Design: Identification of all approved HIV/AIDS and AIDS-related conditions drugs between 1987 and 1999. Follow-up of postmarketing study requirements in the approval letters addressed to the manufacturers. Setting: Accelerated approval has been expanded to other disease conditions in the past decade. Intervention: Request of approval letters from the U.S. Food and Drug Administration for 76 regulatory actions including expanded access and accelerated and traditional approvals for 42 drugs under the Freedom of Information Act (FOIA) between September 1998 and October 1999. Main Outcome Measure(s): Obtainability of approval letters and uncensored postmarketing study requirements. Results: Fifty-five approval letters were received. Postmarketing study commitments of manufacturers were censored in 25 letters received. We were unable to obtain uncensored copies of those approval letters as of May 2000. Censoring was associated with whether (1) the Prescription Drug User Fee Act of 1992 was applicable to the drug (odds ratio (OR) = 5.7,95% confidence interval (CI) = 1.4-23.7) and (2) the new drug application was for a new molecular entity or new drug formulation (OR = 4.2, 95% CI = 1.3-13.6). Conclusions: Continued secrecy may stifle independent research and hinder health care providers and patients in making informed decisions.