Factors influencing uptake of pharmacogenetic testing in a diverse patient population.

BACKGROUND: The successful integration of pharmacogenetic (PGx) testing into clinical care will require attention to patient attitudes. In this study, we aimed to identify the major reasons why patients would or would not consider PGx testing and whether these factors differed by race, socioeconomic and insurance status, and medical history. METHODS: We developed and conducted a survey within the adult patient population of the Duke Family Medicine Center. RESULTS: Of 75 completed surveys (65% African-American), 77% indicated they were 'very likely' or 'somewhat likely' to take a PGx test. Respondents who had experienced a side effect were significantly more likely to indicate they would take a PGx test and expressed greater interest in learning more about testing than those who had not. Drug safety and effectiveness were the major reasons to have PGx testing. Privacy concerns and lack of insurance coverage for testing were the major reasons to decline testing. CONCLUSIONS: We found no differences in interest in PGx tests by race or socioeconomic status, but found stronger interest from those with a history of side effects and private insurance. While the overall support of PGx testing is encouraging, greater reassurance of medical privacy and development of educational resources are needed.

Pharmacogenomics, evidence, and the role of payers.

Initial enthusiasm for the potential of pharmacogenomics (PGx) to transform medical practice has been tempered by the reality that the process of biomarker discovery, validation, and clinical qualification has been disappointingly slow, with a limited number of PGx tests entering the marketplace since the initial publication of the human genome sequence. Reasons for the delays include the complexity of the underlying science as well as clinical, economic, and organizational barriers to the effective delivery of personalized health care. Nevertheless, payers are interested in using PGx services to ensure that drug use is safer and more effective, particularly in the settings of medications that are widely used, have significant risks of serious adverse events, have poor or highly variable drug response, or are very expensive. However, public and private payers have specific evidence requirements for new health care technologies that must be met prior to obtaining favorable coverage and reimbursement status. These evaluation criteria are frequently more rigorous than the current level of evidence required for regulatory approval of new PGx tests or PGx-related drug labeling. To support payer decision-making, researchers will need to measure the impact of PGx testing on clinical and economic outcomes and demonstrate the net benefit of PGx testing as compared to usual care. By linking payer information needs with the current PGx research agenda, there is the opportunity to develop the data required for informed decision-making. This strategy will increase the likelihood that PGx services will be both reimbursed and used appropriately in clinical practice.

Harnessing economic drivers for successful clinical implementation of pharmacogenetic testing.

Before pharmacogenetic (PGx) testing has a major impact on clinical practice, two levels of evidence must be generated. First, studies demonstrating the links between genetic variation and response to medications in defined populations are needed, along with development of valid tests to measure these specific variants. Second, studies should be conducted to evaluate whether PGx testing improves health outcomes for patients and whether the decision to test is cost-effective relative to usual care. This latter set of questions is typically of greatest relevance to clinicians and payers, the ultimate gatekeepers for the clinical integration of pharmacogenetics. To date, nearly all of the research efforts and funding for PGx have been focused on the first set of issues-getting the science right. However, now is the time to increase our research efforts on the second set of issues-to improve the PGx evidence base for both clinical and economic decision making.

Integrating molecular medicine into the US health-care system: opportunities, barriers, and policy challenges.

Scientific support about the concept of using molecular data for risk stratification and tailoring health-care interventions to the individual--a strategy broadly defined as molecular medicine (MM)--is accumulating. Molecular-based health-care technologies are beginning to enter clinical practice, but their use has revealed many scientific, economic, and organizational barriers to the effective delivery of targeted health care. We conducted a qualitative interview study to describe the MM landscape, with an emphasis on eliciting policy recommendations for the field from a broad range of stakeholders in MM and health care. Molecular medicine has widespread support but will require changes in how molecular-based technologies are evaluated, how health care is financed and delivered, and how clinicians and consumers are trained and prepared for its use. In particular, researchers and developers need to become active participants in a variety of clinical integration strategies to realize the promise of MM.

Identification of resource use and associated costs for viral meningitis.

PURPOSE: This study involved identifying resource use and assigning monetary value to the diagnostic work-up and management of viral meningitis. METHODOLOGY: Using a previously established decision analytic framework, various resources were identified as part of routine management of viral meningitis. Secondary database analyses were used to quantify resources and assign a monetary value as a part of routine management of viral meningitis requiring use of the resource units identified in the decision analytic framework. Discharge data sources from the states of California, Florida, and Illinois, and Medicaid data sources from the state of Pennsylvania, were used for the purpose of analysis. PRINCIPAL FINDINGS: Physician visits, emergency room visits, hospital admissions, procedures, and medications were identified as the major resource used. Lumbar punctures, CT scans, and antibiotics were identified as the major procedures and medications utilized. No significant difference was found in the major resources used between the states' discharge data and the Medicaid data sources. The mean total charges for patient admissions with CT scans were significantly higher than for patient admissions without CT scans ($11,531.80 vs $7,841.30, P < 0.05). The mean lengths of stay for patients with CT scan were significantly higher than for patient admissions without CT scans (4.71 days vs. 3.88 days, P < 0.05). The patient readmission rate was 10.7 percent, while the readmission rate for episodes with more than one hospitalization was 11.1 percent. The mean charge associated with readmission was $12,200.

Beyond survey data: a claims-based analysis of drug use and spending by the elderly.

Previous estimates of Medicare beneficiaries total and out-of-pocket spending on outpatient prescription drugs have largely been based on data from the 1995 Medicare Current Beneficiary Survey and have focused on how expenditures vary among beneficiaries with different demographic characteristics. This paper reports the results of an analysis of prescription claims from 1998 for more than 375,000 elderly persons whose prescription benefit was managed by Merck-Medco Managed Care. In addition to examining how total and out-of-pocket drug spending in a well-insured population varies by age and sex, we report how total and condition-specific drug spending varies for elderly persons with ten common chronic diseases. Our results illustrate the highly skewed nature of prescription drug spending, even among those with drug coverage, and underscore the particularly high cost burden that pharmaceuticals place on elderly people with chronic diseases.

The cost-effectiveness of terazosin and placebo in the treatment of moderate to severe benign prostatic hyperplasia.

OBJECTIVES: To evaluate the cost-effectiveness and functional status effects of terazosin, an alpha(1)-adrenoceptor antagonist, compared with placebo in the treatment of men with moderate to severe, symptomatic, benign prostatic hyperplasia (BPH). METHODS: Prospective, randomized, double-blind, placebo-controlled multicenter trial of 2084 patients was conducted at 15 academic regional centers and 141 community-based satellite centers. Information about the use of health care resources and non-disease-specific functional status measures was collected by a standardized telephone interview of patients at baseline and every month thereafter for 12 months. Other information, such as American Urologic Association (AUA) disease-specific functional status scores, was obtained from the patient study records. Patients had a mean age of 65.7 years (range, 46 to 94), with a clinical diagnosis of BPH. At baseline men had at least moderate BPH symptoms by AUA Symptom score (13 or more) and Bother Score (8 or more). On entry, patients at regional sites had peak urinary flow rates 15 mL/s or less and total voided urine volumes 150 mL or greater. A total of 1053 patients were randomized to terazosin and 1031 to placebo treatment. Primary outcome measures included payments for all direct medical resource consumption (inpatient care, emergency department care, outpatient care, and medications); changes in three AUA disease-specific functional status indicators, (Symptom, Bother, and Quality of Life scores), and non-disease-specific functional status measures (days of work loss, days of customary activity loss, and days of bed rest). RESULTS: Total payments for health care resource (including study drug medication), adjusted to reflect 1000 patients per treatment group, were $3,781,803 and $3,568,263 in the placebo and terazosin groups, respectively. All three AUA disease-specific functional status scores improved significantly more in the terazosin group than in the placebo group. We found no difference between terazosin and placebo in all three nonspecific functional status measures. CONCLUSIONS: Compared with placebo, terazosin therapy for moderate to severe symptomatic BPH results in approximately equivalent payments for direct medical care, better disease-specific functional status improvement, and comparable change in non-disease-specific functional status measures.

Effect of demographic factors, urinary peak flow rates, and Boyarsky symptom scores on patient treatment choice in benign prostatic hyperplasia.

OBJECTIVES: To determine the effect of patient's age, race, Boyarsky score, and urinary flow rate on type of treatment selected for benign prostatic hyperplasia (BPH) and to evaluate maintenance of treatment at 1-year follow-up. METHODS: Subjects in this prospective study, conducted in a referral center prostate clinic, were 174 consecutive patients, aged 67.6 +/- 10.8 years (mean +/- SD), with previously untreated BPH. Patients underwent structured interviews and uroflowmetry, then completed the Boyarsky Symptom Index. Blinded to these data, one physician described four treatment categories in a nonjudgmental fashion, always using the same order: watchful waiting; finasteride and alpha-blocker; thermal therapy, balloon dilation, and a prostate stent; and transurethral prostate resection. Treatment choice was entirely that of the patient. Independent variables were patient's age, race, symptom score, and uroflow; the dependent variable was treatment choice. At 1 year, the same physician interviewed patients to evaluate maintenance of therapy. RESULTS: Only symptom score and flow rate were predictive of treatment choice, high scores and low flow being associated with more aggressive treatment choices (P = 0.001). Most patients, regardless of symptom severity, chose interventions less aggressive than surgery and more aggressive than watchful waiting. At 1 year, 85% of patients continued to be maintained on their original treatment. CONCLUSIONS: Men with mild or moderate BPH prefer interventions of moderate aggressiveness; race and age make little or no difference. If maintenance of treatment indicates patient satisfaction, most patients appear to remain satisfied with therapy they select.

The costs of prostatectomy for benign prostatic hyperplasia.

Using claims data for a 5% random sample of Medicare beneficiaries, we estimated the costs of surgical treatment for benign prostatic hyperplasia (BPH), including those related to the initial prostatectomy, the treatment of postsurgical complications, and reoperation within one year. We identified 14,480 men who underwent prostatectomy for BPH during 1986-1987, including 13,730 transurethral and 750 open procedures. Mean total inpatient costs (including all hospital charges and professional service fees) for these procedures were estimated to be $6,501 and $10,223, respectively. Among patients who underwent transurethral and open prostatectomy, we identified 938 (6.8%) and 39 (5.2%) individuals who had at least one readmission for postsurgical complications or reoperation. Total expected costs of transurethral and open prostatectomy, inclusive of readmissions for complications and reoperations within one year, were estimated to be $6,823 and $10,477, respectively. Our study indicates the economic burden represented by surgical treatment of BPH.

Validation of a new quality of life questionnaire for benign prostatic hyperplasia.

In planning a longitudinal study to characterize the natural history of benign prostatic hyperplasia (BPH), we validated a new disease-specific quality of life questionnaire in a pilot study. We studied 110 men in Rochester, Minnesota who spanned the severity of BPH, from men with no known BPH to men who underwent surgery for this condition. Baseline data were obtained on all men, and the 30 who underwent prostatectomy were re-interviewed to test responsiveness. Reproducibility was examined on the pre-post responses (10 weeks apart) of the 37 men with BPH who did not undergo prostatectomy. Six of twelve question domains were retained in the final questionnaire on the basis of their responsiveness to change, reproducibility, internal consistency, and validity. These were: urinary symptoms, degree of bother due to urinary symptoms, BPH-specific interference with activities, general psychological well-being, worries and concerns, and sexual satisfaction. Most of the more generic measures were deleted.

Urinary symptom and quality of life questions indicative of obstructive benign prostatic hyperplasia. Results of a pilot study.

In a pilot study of a urinary symptom and health-related quality-of-life questionnaire for benign prostatic hyperplasia (BPH), responses from 64 Mayo Clinic patients with cystoscopic evidence of obstructive BPH were compared with those of 14 men with no cystoscopic evidence of BPH and a community sample of 64 comparably aged men with no medical history of prostate enlargement. Questions which best discriminated between the groups were those dealing with urinary symptom frequency, bother due to urinary symptoms, and worry and concern about urinary problems. The results suggest that urinary-symptom-bother and worry due to urinary symptoms may be important additions to the more usual questions asked about urinary frequency in the identification of men with BPH. These findings are preliminary, however, and will be verified in an ongoing natural history study of BPH.