Assessment of the impact of a patient clinical trials handbook among pharmacy students.

BACKGROUND: Patient education in the basic concepts of clinical trials is necessary to promote understanding of the informed consent process and enhance patients' decision-making. It has been suggested that patients' knowledge and attitudes are improved by being given general written information about clinical trials. OBJECTIVE: This pilot study was conducted to determine the effect of a patient education handbook on the knowledge, attitudes, and motivations of pharmacy students regarding clinical trials. METHODS: A patient clinical trials handbook was developed at a 7th-grade reading level for the Department of Veterans Affairs Cooperative Studies Program and tested in PharmD students. Students were randomized to the experimental group (received handbook) or the control group (no handbook). They were given 15 to 20 minutes to read the handbook, after which they were asked to respond to a questionnaire adapted from previous studies. The questionnaire included 25 true/false questions testing participants' knowledge of clinical trials, 5 questions on attitudes toward clinical trials scored on a 5-point Likert scale, and 6 questions concerning their motivation toward participation in hypothetical clinical trial scenarios scored on a 5-point Likert scale. The experimental group was also asked to rate the informativeness, helpfulness, and clarity of the handbook on a 5-point Likert scale. RESULTS: There were 40 students in the experimental group and 50 in the control group. Knowledge scores were significantly higher in the experimental group compared with the control group (mean [SD] percentage of correct answers, 88.7% [8.0%] vs 82.6% [9.0%], respectively; P < 0.001). Positive attitudes toward clinical trials were also increased in the experimental group compared with the control group; specifically, participants expressed significantly greater clarity of understanding of clinical trials (mean score, 1.4 [0.5] vs 0.8 [0.6]; P < 0.001) and relief associated with knowing about clinical trials (mean score, 0.8 [0.8] vs 0.4 [0.7]; P = 0.017). There were no between-group differences in students' motivation to participate in the hypothetical clinical trial scenarios. A high proportion of students (95%) found the handbook informative, helpful, and understandable. CONCLUSIONS: The patient clinical trials handbook increased knowledge and positive attitudes regarding clinical trials among pharmacy students participating in this study.

Cost-effectiveness of gemfibrozil for coronary heart disease patients with low levels of high-density lipoprotein cholesterol: the Department of Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial.

BACKGROUND: Although numerous clinical trials and economic analyses have established the efficacy and cost-effectiveness of lowering cholesterol for the prevention of coronary heart disease, there are few data on the role of raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglyceride levels. The US Department of Veterans Affairs (VA) Cooperative Studies Program HDL-C Intervention Trial (VA-HIT) was a multicenter, randomized trial of gemfibrozil, an agent that raised HDL-C levels and lowered triglyceride levels, yet had no effect on low-density lipoprotein cholesterol (LDL-C) levels. The study showed that gemfibrozil therapy significantly reduced major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in patients with coronary heart disease, low HDL-C levels, and low LDL-C levels. OBJECTIVE: To report the results of a cost-effectiveness study based on the results of the VA-HIT. METHODS: The cost per year of life gained with gemfibrozil therapy was calculated. Hazard functions were estimated, and the resulting probabilities were used in a Markov model simulation to estimate the effect of gemfibrozil on life expectancy and costs over a simulated lifetime. Sensitivity analyses were used to account for uncertainty. RESULTS: Using the prices of gemfibrozil that were negotiated by the VA, gemfibrozil was cost saving. Using drug prices found outside the VA, a quality-adjusted life-year saved by gemfibrozil therapy cost between $6300 and $17 100. CONCLUSIONS: Gemfibrozil reduces major cardiovascular events in male coronary heart disease patients with low levels of HDL-C and low levels of LDL-C and would result in cost saving at annual drug costs of $100 or less in 1998 dollars. Even at the higher drug prices represented by the average wholesale price in the United States, the cost of a life-year saved is well below the threshold that would be deemed cost-effective. To our knowledge, this is the first economic analysis based on clinical trial data to assess the cost-effectiveness of raising HDL-C levels and lowering triglyceride levels in a setting in which LDL-C levels were not lowered.

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]).

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

Chondroitin product selection for the glucosamine/chondroitin arthritis intervention trial.

OBJECTIVE: To select a high-quality chondroitin dosage form and/or an appropriate source of sodium chondroitin for the National Institutes of Health's Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT). DESIGN: Controlled experimental trials. SETTING: Laboratory. PATIENTS OR PARTICIPANTS: Not applicable. INTERVENTIONS: Commercially available chondroitin products were reviewed, and purified sodium chondroitin from two suppliers was evaluated through tests (infrared and near-infrared identification, moisture content, pH, optical rotation, color and clarity of aqueous solutions prepared from the powders, protein contamination, total residue following ignition and nitrogen content, determination of sodium chondroitin molecular weight, disaccharide analysis, and measurement of chondroitin, sodium, and total glycosaminoglycan content) and an onsite supplier audit. MAIN OUTCOME MEASURES: Purity, potency, and quality of sodium chondroitin powders. RESULTS: No commercially available chondroitin product was deemed appropriate for use in GAIT. Samples of sodium chondroitin powder from two suppliers exhibited similar disaccharide and glycosaminoglycan content. Each contained approximately 2% hyaluronic acid and 8%-9% unsulfated disaccharide. Potency was inconsistent across groups, which might have resulted from different analytical methods and choice of reference standard. Mean potency obtained by five separate methods ranged from 82.2% to 95.5% for one supplier, 92.5% to 110.1% for another, and 95.1% to 112.5% for a commercially obtained reference standard. Critical issues raised by the results include choice of reference standard, selection of assay method, and the consistent appearance of an unidentifiable contaminant present in all three lots from one supplier. CONCLUSION: This blinded study determined methods to identify acceptable agents and provided results, which, in addition to regulatory compliance supplier audits, formed the basis for chondroitin product selection in GAIT.

The prophylaxis of medical patients for thromboembolism pilot study.

PURPOSE: We assessed the feasibility of a large randomized trial intended to determine whether low-dose heparin prophylaxis given throughout hospitalization reduces mortality and morbidity in general medical patients. SUBJECTS AND METHODS: Hospitalized general medical patients aged more than 60 years at 5 Department of Veterans Affairs (VA) medical centers were randomized to receive enoxaparin 40 mg or identical placebo, given daily by subcutaneous injection until hospital discharge. Outcomes included total mortality at 90 days (the primary outcome) and 1 year, and occurrence in the VA hospital within 90 days of symptomatic deep venous thrombosis, pulmonary embolism, and major bleeding. RESULTS: Only 7.6% of hospitalized patients aged more than 60 years were eligible for the study, although a chart review had predicted 25%. The principal exclusions were prior indication for anticoagulation, anticipated need for anticoagulation, contraindication to heparin, expected hospitalization less than 3 days, and "supportive/palliative care only" status. We randomized 140 patients into each group, 28% of target recruitment. The groups were well matched by age and comorbidities. Death occurred in 13 patients receiving enoxaparin and 14 patients receiving placebo at 90 days (relative risk 0.93, 95% confidence interval 0.26-1.59), and in 36 and 32 patients, respectively, at 1 year (relative risk 1.13, 95% confidence interval 0.66-1.60). Clinical thromboembolic events occurred in 5 patients receiving enoxaparin and 8 patients receiving placebo, and major bleeding occurred in 2 and 5 patients, respectively. CONCLUSIONS: The pilot study indicated that the full study was not feasible. The decision to use prophylaxis pertains to only a small proportion of general medical patients hospitalized at VA medical centers, and this proportion is overestimated by chart review. The effect of low-dose heparin prophylaxis on clinical outcomes in hospitalized general medical patients remains uncertain.

Opioid dependence treatment, including buprenorphine/naloxone.

OBJECTIVE: To review opioid dependence (OD) and its treatment. Pharmacologic treatments, including the use of buprenorphine/naloxone, are presented. Pharmaceutical care functions for outpatient OD treatment are discussed. DATA SOURCES: Primary and review articles were identified by MEDLINE and HEALTHSTAR searches (from 1966 to November 2000) and through secondary sources. Tertiary sources were also reviewed regarding general concepts of OD and its treatment. STUDY SELECTION/DATA EXTRACTION: Relevant articles were reviewed after identification from published abstracts. Articles were selected based on the objectives for this article. Studies of the treatment of OD with buprenorphine were selected based on the topic (pharmacology, pharmacokinetics, adverse reactions) and study design (randomized, controlled clinical trials in patients with OD with active/placebo comparisons and/or comparisons of active OD treatments). Articles regarding pharmacists' activities in the treatment and prevention of OD were reviewed for the pharmaceutical care section. DATA SYNTHESIS: OD is considered a medical disorder with costly adverse health outcomes. Although methadone maintenance treatment (MMT) is cost-effective for OD, only about 12% of individuals with OD receive this treatment. Psychological and pharmacologic modalities are used to treat OD, but patients often relapse. Drug therapy includes alpha 2-agonists for withdrawal symptoms, detoxification regimens with or without opioids, opioid antagonists, and opioid replacement including methadone, levomethadyl acetate, and buprenorphine. The Drug Addiction Treatment Act of 1999 allows for office-based opioid replacement therapies. Sublingual buprenorphine with naloxone can be used in this milieu. Buprenorphine with naloxone is currently under new drug application review with the Food and Drug Administration. Clinical research shows buprenorphine to be equal in effectiveness to methadone, but safer in overdose due to its ceiling effect on respiratory depression. It has lower abuse potential and fewer withdrawal symptoms when discontinued. Naloxone is included to decrease diversion and injection of the tablets. Pharmacists in outpatient settings who are familiar with OD have opportunities to provide pharmaceutical care to patients receiving this treatment. Pharmaceutical care functions for OD include ensuring appropriate drug administration, monitoring adverse effects, alleviating withdrawal symptoms, treating intercurrent illnesses, minimizing diversion, and preventing relapse. CONCLUSIONS: OD is a critical unmet health problem in the US. Buprenorphine combined with naloxone represents an innovative treatment for OD in outpatient settings. This new treatment has advantages over MMT.

The role of the pharmacy coordinating center in the DIG trial.

Large simple trials (LSTs) emerged in response to the need for large sample sizes to answer important clinical questions in which treatments have a moderate effect on clinical endpoints. Between 1991 and 1996 the National Heart, Lung, and Blood Institute and the Department of Veterans Affairs (VA) Cooperative Studies Program conducted an LST entitled "Digitalis Investigation Group (DIG): Trial to Evaluate the Effect of Digitalis on Mortality in Heart Failure." The VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center served as the DIG pharmacy coordinating center (PCC). As a direct result of involvement in the DIG trial, the PCC identified the need for an increased emphasis on computerization and automated support of clinical trials, especially LSTs.