Uptake and utilization of directly acting antiviral medications for hepatitis C infection in U.S. veterans.

New drugs therapies have revolutionized the treatment of hepatitis C virus (HCV) infection. The objectives of this study were to evaluate uptake and utilization of boceprevir and telaprevir in the Department of Veterans Affairs (VA). We evaluated whether therapies conformed to response-guided protocols, whether they replaced standard interferon plus ribavirin treatment, and whether IL-28B was used to guide treatment. We performed an administrative data-based analysis of all patients receiving pharmacologic treatment for HCV in VA from October 2009 to July 2013. There were 12 737 new HCV prescriptions in VA during this time, with 5564 boceprevir or telaprevir prescriptions (44%) and 7173 prescriptions (56%) written for standard interferon plus ribavirin treatment. Prescriptions for the new treatments heavily favoured boceprevir vs telaprevir (83% vs 17%). Sixty-two percent (62%) of boceprevir-treated patients completed their minimum-specified protocol, while 69.2% of telaprevir-treated patients completed their minimum-specified protocol. From October 2010 to July 2012, 4090 patients had an IL-28B test; less than 16% of these tests guided subsequent HCV prescriptions. Uptake of boceprevir and telaprevir was rapid; the number of patients initiating treatment approximately doubled in the period after their introduction. While new prescriptions favor boceprevir or telaprevir over standard interferon plus ribavirin therapy, there appears to still be a strong role of interferon plus ribavirin in treating HCV patients. This work can inform our understanding of how other new effective HCV therapies will be used, their diffusion, and the timing of their diffusion in actual clinical practice.

A randomized trial of computer-based reminders and audit and feedback to improve HIV screening in a primary care setting.

Despite recommendations for voluntary HIV screening, few medical centres have implemented screening programmes. The objective of the study was to determine whether an intervention with computer-based reminders and feedback would increase screening for HIV in a Department of Veterans Affairs (VA) health-care system. The design of the study was a randomized controlled trial at five primary care clinics at the VA Palo Alto Health Care System. All primary care providers were eligible to participate in the study. The study intervention was computer-based reminders to either assess HIV risk behaviours or to offer HIV testing; feedback on adherence to reminders was provided. The main outcome measure was the difference in HIV testing rates between intervention and control group providers. The control group providers tested 1.0% (n = 67) and 1.4% (n = 106) of patients in the preintervention and intervention period, respectively; intervention providers tested 1.8% (n = 98) and 1.9% (n = 114), respectively (P = 0.75). In our random sample of 753 untested patients, 204 (27%) had documented risk behaviours. Providers were more likely to adhere to reminders to test rather than with reminders to perform risk assessment (11% versus 5%, P < 0.01). Sixty-one percent of providers felt that lack of time prevented risk assessment. In conclusion, in primary care clinics in our setting, HIV testing rates were low. Providers were unaware of the high rates of risky behaviour in their patient population and perceived important barriers to testing. Low-intensity clinical reminders and feedback did not increase rates of screening.

Cost-effectiveness of voluntary HIV screening in Russia.

Russia has one of the world's fastest growing HIV epidemics, and HIV screening has been widespread. Whether such screening is an effective use of resources is unclear. We used epidemiologic and economic data from Russia to develop a Markov model to estimate costs, quality of life and survival associated with a voluntary HIV screening programme compared with no screening in Russia. We measured discounted lifetime health-care costs and quality-adjusted life years (QALYs) gained. We varied our inputs in sensitivity analysis. Early identification of HIV through screening provided a substantial benefit to persons with HIV, increasing life expectancy by 2.1 years and 1.7 QALYs. At a base-case prevalence of 1.2%, once-per-lifetime screening cost $13,396 per QALY gained, exclusive of benefit from reduced transmission. Cost-effectiveness of screening remained favourable until prevalence dropped below 0.04%. When HIV-transmission-related costs and benefits were included, once-per-lifetime screening cost $6910 per QALY gained and screening every two years cost $27,696 per QALY gained. An important determinant of the cost-effectiveness of screening was effectiveness of counselling about risk reduction. Early identification of HIV infection through screening in Russia is effective and cost-effective in all but the lowest prevalence groups.

Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules.

BACKGROUND: Effective strategies for managing patients with solitary pulmonary nodules (SPN) depend critically on the pre-test probability of malignancy. OBJECTIVE: To validate two previously developed models that estimate the probability that an indeterminate SPN is malignant, based on clinical characteristics and radiographic findings. METHODS: Data on age, smoking and cancer history, nodule size, location and spiculation were collected retrospectively from the medical records of 151 veterans (145 men, 6 women; age range 39-87 years) with an SPN measuring 7-30 mm (inclusive) and a final diagnosis established by histopathology or 2-year follow-up. Each patient's final diagnosis was compared with the probability of malignancy predicted by two models: one developed by investigators at the Mayo Clinic and the other developed from patients enrolled in a VA Cooperative Study. The accuracy of each model was assessed by calculating areas under the receiver operating characteristic (ROC) curve and the models were calibrated by comparing predicted and observed rates of malignancy. RESULTS: The area under the ROC curve for the Mayo Clinic model (0.80; 95% CI 0.72 to 0.88) was higher than that of the VA model (0.73; 95% CI 0.64 to 0.82), but this difference was not statistically significant (Delta = 0.07; 95% CI -0.03 to 0.16). Calibration curves showed that the probability of malignancy was underestimated by the Mayo Clinic model and overestimated by the VA model. CONCLUSIONS: Two existing prediction models are sufficiently accurate to guide decisions about the selection and interpretation of subsequent diagnostic tests in patients with SPNs, although clinicians should also consider the prevalence of malignancy in their practice setting when choosing a model.

Cost-effectiveness of HIV screening in acute care settings.

BACKGROUND: Although screening inpatients for human immunodeficiency virus (HIV) in acute care hospital settings has been recommended, the cost-effectiveness of screening is not known. OBJECTIVE: To estimate the cost-effectiveness of a voluntary screening program in acute care hospitals and associated clinics. RESULTS: During the first year, an HIV screening program implemented in acute care hospital settings in which the seroprevalence of HIV infection is 1% or more would result in the identification of approximately 110,000 undetected cases of HIV infection. The program would result in expenditures of approximately $171 million for testing and counseling, and expenditures of approximately $2 billion for incremental medical care for the patients identified as having HIV infection during the first year of screening. When the seroprevalence of HIV is 1%, the cost-effectiveness of screening is $47,200 per year of life saved. When the effect of early identification of HIV infection on the patient's quality of life also is considered, screening is less cost-effective. Screening-induced reductions in risk behavior improve the cost-effectiveness of screening by preventing the transmission of HIV.

The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life.

BACKGROUND: Because most strokes cause neurological impairment rather than death, stroke prophylaxis may improve quality of life more than length of life. Thus, an understanding of how stroke and stroke prophylaxis affect quality of life is central to clinical decision making for many patients. METHODS: We elicited quality-of-life estimates, known as utilities, for 3 degrees of severity of anticipated stroke-mild, moderate, and major- and for stroke prophylaxis with either warfarin sodium or aspirin therapy. We used the time tradeoff and standard gamble methods to elicit these utilities from 83 patients who had atrial fibrillation. RESULTS: Seventy patients completed the interview successfully. Their utilities for stroke ranged from worse than death (< 0) to as good as current health (1.0). The median utilities for mild, moderate, and major stroke were 0.94, 0.07, and 0.0, respectively. Although the median utilities decreased with increasing severity of stroke (P < .001), there was high interpatient variability within each degree of stroke severity. For example, 7 subjects (10%) rated a major stroke above 0.5, while 58 subjects (83%) rated it as equal to or worse than death. In contrast to the stroke utilities, the median utilities for warfarin and aspirin therapy were high-0.997 and 1.0, respectively. However, the interpatient variability for warfarin therapy was also important: 11 patients (16%) with atrial fibrillation rated the utility of warfarin therapy so low that their quality-adjusted life expectancy would be greater with aspirin. CONCLUSION: Patients' utilities for stroke prophylaxis and anticipated stroke vary substantially. Many patients view the quality of life with major stroke as tantamount to or worse than death. These findings highlight the relevance of incorporating patient preferences when choosing stroke prophylaxis.

Screening women of childbearing age for human immunodeficiency virus. A cost-benefit analysis.

In light of the increasing problem of perinatal human immunodeficiency virus (HIV) transmission, the issue of screening women for HIV is receiving considerable attention. We analyzed the costs and benefits of screening women of childbearing age for HIV. The analysis was based on a dynamic model of the HIV epidemic that incorporated disease transmission and progression, behavioral changes, and effects of screening and counseling. We found that the primary benefit of screening programs targeted to women of childbearing age lies not in the prevention of HIV infection in their newborns but in the prevention of infection in their adult contacts. Because of this benefit, screening medium- and high-risk women is likely to be cost-beneficial over a wide range of assumptions about program cost and behavioral changes in response to screening.

Population effects of preventive and therapeutic HIV vaccines in early- and late-stage epidemics.

OBJECTIVE: To evaluate the population effects of potential preventive and therapeutic vaccines in early- and late-stage epidemics in a population of homosexual men. METHODS: An epidemic model was used that simulated the course of the epidemic for a population of homosexual men in San Francisco, California. Vaccine programs were evaluated by the number of cases of HIV averted, the effect on the prevalence of HIV, and by the gain in quality-adjusted life years (QALY) for the total population. RESULTS: In the model, a preventive vaccine prevented 3877 cases of HIV infection during a 20-year period, reduced the projected prevalence of HIV infection from 12 to 7% in a late-stage epidemic, and gained 15,908 QALY. A therapeutic vaccine that did not affect the infectivity of vaccine recipients increased the number of cases of HIV infection by 210, resulted in a slight increase in the prevalence of HIV infection from 12 to 15% in a late-stage epidemic, and gained 8854 QALY. If therapeutic vaccines reduced infectivity, their use could produce net gains of QALY in the population that were similar to gains from the use of preventive vaccines. In an early-stage epidemic, the advantage of a preventive vaccine program relative to a therapeutic vaccine program was markedly enhanced. CONCLUSIONS: Both preventive and therapeutic vaccine programs provided substantial benefit, but their relative merit depended on which outcome measures were assessed. Evaluation of HIV vaccine programs based solely on cases averted or on prevalence of HIV in the population underestimates the benefit associated with therapeutic vaccine programs. The effect of a therapeutic HIV vaccine on the epidemic outcomes depended markedly on whether the therapeutic vaccine reduced the infectivity of the vaccine recipient. The relative merits of preventive and therapeutic vaccines depend on the stage of the epidemic. Field vaccine trials should evaluate correlates of infectivity, such as HIV viral load. HIV vaccine implementation strategies should be tailored to the dynamics of the epidemic in specific populations.

Occupational exposure to human immunodeficiency virus and hepatitis B virus: a comparative analysis of risk.

OBJECTIVE: To estimate the occupational risk from infection with the human immunodeficiency virus (HIV) in terms of loss of (quality-adjusted) life expectancy, and to compare that risk to those posed by other hazards faced by health care workers. DESIGN: Decision-analytic model. RESULTS: For a 30-year-old female health care worker (unvaccinated for hepatitis B virus [HBV]), the loss of life expectancy from a needlestick from a symptomatic HIV-positive (HIV+) patient is 39 days (range, 17 to 93 days), as compared with a loss of 17 days from a needlestick from a patient who is hepatitis-B-surface-antigen-positive (HBsAg+), and 38 days from a needlestick from a patient who is hepatitis-B-e-antigen-positive (HBeAg+). When morbidity is included in the analysis of risk (through calculation of the quality-adjusted loss of life expectancy), the risk from both HBV and HIV increases. The quality-adjusted loss of life expectancy due to a needlestick exposure from a symptomatic HIV+ patient is 45 days (range, 20 to 108 days), as compared with a quality-adjusted loss of life expectancy of 48 days from a needlestick from an HBsAg+ patient, and 109 days from a needlestick from a patient who is known to be HBeAg+. By comparison, a cross-country automobile trip is associated with a loss of life expectancy of approximately 1 day. The 45- to 50-day loss of quality-adjusted life expectancy from percutaneous exposures to HIV and HBV is approximately the same magnitude as the gain in life expectancy from 10 years of annual screening for breast cancer with mammography and physical examination. CONCLUSIONS: The risk associated with percutaneous exposures to symptomatic HIV+ patients is comparable to other risks that health care workers have faced knowingly and have accepted in the recent past. However, the loss of quality-adjusted life expectancy associated with a needlestick exposure is significant. Identification of cost-effective methods that increase the safety of medical personnel but also ensure full access to high-quality care for HIV+ patients should be a high priority.

Echocardiography in patients with suspected endocarditis: a cost-effectiveness analysis.

PURPOSE: We sought to determine the appropriate use of echocardiography for patients with suspected endocarditis. PATIENTS AND METHODS: We constructed a decision tree and Markov model using published data to simulate the outcomes and costs of care for patients with suspected endocarditis. RESULTS: Transesophageal imaging was optimal for patients who had a prior probability of endocarditis that is observed commonly in clinical practice (4% to 60%). In our base-case analysis (a 45-year-old man with a prior probability of endocarditis of 20%), use of transesophageal imaging improved quality-adjusted life expectancy (QALYs) by 9 days and reduced costs by $18 per person compared with the use of transthoracic echocardiography. Sequential test strategies that reserved the use of transesophageal echocardiography for patients who had an inadequate transthoracic study provided similar QALYs compared with the use of transesophageal echocardiography alone, but cost $230 to $250 more. For patients with prior probabilities of endocarditis greater than 60%, the optimal strategy is to treat for endocarditis without reliance on echocardiography for diagnosis. Patients with a prior probability of less than 2% should receive treatment for bacteremia without imaging. Transthoracic imaging was optimal for only a narrow range of prior probabilities (2% or 3%) of endocarditis. CONCLUSION: The appropriate use of echocardiography depends on the prior probability of endocarditis. For patients whose prior probability of endocarditis is 4% to 60%, initial use of transesophageal echocardiography provides the greatest quality-adjusted survival at a cost that is within the range for commonly accepted health interventions.

Projected long-term costs of coronary stenting in multivessel coronary disease based on the experience of the Bypass Angioplasty Revascularization Investigation (BARI).

BACKGROUND: Stents are now used in the majority of percutaneous coronary revascularization procedures. It is not clear whether the higher initial cost of stenting is later repaid by reducing costly complications and repeat revascularization procedures, especially for patients with multivessel disease. METHODS: To project the long-term costs of using coronary stents, angioplasty, or bypass surgery to treat patients with multivessel coronary artery disease, we developed a decision model based on the outcomes documented in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We studied 2 clinical strategies: provisional stenting of suboptimal PTCA results and primary stenting of all angiographically eligible lesions. The cost of CABG was also updated to reflect contemporary practice. RESULTS: Provisional stenting had lower projected costs over a 4-year period than either traditional PTCA (-$1742, or -3.4%) or contemporary CABG (-$832, or -1.7%), mostly because of reductions in emergency CABG after PTCA. In contrast, primary stenting had higher projected costs over a 4-year period than either PTCA (+$333, or +0. 7%) or contemporary CABG (+$1243, or +2.5%), mainly because of the higher initial procedure costs. These results were not substantially altered when we systematically varied the key parameters of the models in 1-way and 2-way sensitivity analyses. CONCLUSIONS: A primary stenting strategy in patients with multivessel disease has higher projected long-term costs than CABG. In contrast, a provisional stenting strategy in multivessel disease has lower projected costs than either PTCA or CABG.

Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C.

BACKGROUND: Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha-foetoprotein levels is widely practiced. AIM: To evaluate its cost-effectiveness using a Markov decision model. METHODS: Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha-foetoprotein at 6-12-month intervals in 40-year-old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality-adjusted life-year saved. Extensive sensitivity analysis was performed. RESULTS: For the least efficacious strategy, annual alpha-foetoprotein/ultrasonography, the incremental cost-effectiveness ratio (vs. no screening) was $23 043/quality-adjusted life-year. Biannual alpha-foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost-effectiveness ratio of $33 083/quality-adjusted life-year vs. annual alpha-foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha-foetoprotein/ultrasonography, resulted in a cost-effectiveness ratio of $73 789/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography. Biannual alpha-foetoprotein/annual computerized tomography screening resulted in a cost-effectiveness ratio of $51 750/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography screening. CONCLUSIONS: Screening for hepatocellular carcinoma is as cost-effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha-foetoprotein/annual ultrasonography gives the most quality-adjusted life-year gain while still maintaining a cost-effectiveness ratio <$50 000/quality-adjusted life-year. Biannual alpha-foetoprotein/annual computerized tomography screening may be cost-effective.

A randomized controlled trial of a computer-based physician workstation in an outpatient setting: implementation barriers to outcome evaluation.

OBJECTIVE: A research prototype Physician Workstation (PWS) incorporating a graphical user interface and a drug ordering module was compared with the existing hospital information system in an academic Veterans Administration General Medical Clinic. Physicians in the intervention group received recommendations for drug substitutions to reduce costs and were alerted to potential drug interactions. The objective was to evaluate the effect of the PWS on user satisfaction, on health-related outcomes, and on costs. DESIGN: A one-year, two-period, randomized controlled trial with 37 subjects. MEASUREMENTS: Differences in the reliance on noncomputer sources of information, in user satisfaction, in the cost of prescribed medications, and in the rate of clinically relevant drug interactions were assessed. RESULTS: The study subjects logged onto the workstation an average of 6.53 times per provider and used it to generate 2.8% of prescriptions during the intervention period. On a five-point scale (5 = very satisfied, 1 = very dissatisfied), user satisfaction declined in the PWS group (3.44 to 2.98 p = 0.008), and increased in the control group (3.23 to 3.72, p < 0.0001). CONCLUSION: The intervention physicians did not use the PWS frequently enough to influence information-seeking behavior, health outcomes, or cost. The study design did not determine whether the poor usage resulted from satisfaction with the control system, problems using the PWS intervention, or the functions provided by the PWS intervention. Evaluative studies should include provisions to improve the chance of successful implementation as well as to yield maximum information if a negative study occurs.

The release of endogenous amino acids into the vitreous of the intact eye of the albino rat: effect of light, potassium, and ouabain.

The vitreal space of the intact eye of albino rats was perfused in vivo. The concentration of several endogenous amino acids in the vitreal effluent was measured by the [3H]microdansylation procedure. GABA was never detected despite a sensitivity of the method of 0.5 pmol. In contrast to previous results obtained in pigmented rats, photic stimulation with flashing white light did not alter the release of glycine or any of the other amino acids. Potassium (60 mM) and ouabain (0.1 mM) evoked a specific release of glycine. The potassium-evoked release was blocked by magnesium suggesting a neuronal site of origin of glycine. Ouabain-evoked release was not blocked by magnesium. The results were contrasted with experiments on radiolabeled amino acid release from retinas preloaded and superfused in vitro, a condition in which glial localization of exogenous amino acids predominates.

A method for estimating the cost-effectiveness of incorporating patient preferences into practice guidelines.

Many clinical practice guidelines fail to account for the preferences of the individual patient. Approaches that seek to include the preferences of the individual patient in the decision-making process (e.g., interactive videodisks for patient education), however, may incur substantial incremental costs. Developers of clinical practice guidelines must therefore determine whether it is appropriate to make their guidelines flexible with regard to patient preferences. The authors present a formal method for determining the cost-effectiveness of incorporating the preferences of individual patients into clinical practice guidelines. Based on utilities assessed from 37 patients, they apply the method in the setting of mild hypertension. In this example, they estimate that the cost-effectiveness ratio for individualized utility assessment is $48,565 per quality-adjusted year of life, a ratio that compares favorably with other health interventions that are promoted actively. This approach, which can be applied to any clinical domain, offers a formal method for determining whether the incorporation of individual patient preferences is important clinically and is justified economically.

Use of influence diagrams to structure medical decisions.

Influence diagrams are compact representations of decision problems that are mathematically equivalent to decision trees. The authors present five important principles for structuring a decision as an influence diagram: 1) start at the value node and work back to the decision nodes; 2) draw the arcs in the direction that makes the probabilities easiest to assess; 3) use informational arcs to specify which events will have been observed at the time each decision is made; 4) ensure that missing arcs reflect intentional assertions about conditional independence and the timing of observations; and 5) ensure that there are no cycles in the influence diagram. They then build an influence diagram for the problem of staging non-small-cell lung cancer as an illustration. Influence diagrams offer several strengths for structuring medical decisions. They represent graphically and compactly the probabilistic relationships between parameters in the model. Influence diagrams also allow the model to be structured in a fashion that eases the necessary probability assessments, regardless of whether the assessments are based on available evidence or on expert judgment. Influence diagrams provide an important complement to decision trees, especially for representing probabilistic relationships among variables in a decision model.

A normative analytic framework for development of practice guidelines for specific clinical populations.

BACKGROUND: A central problem in practice guideline development is how to develop guidelines that appropriately account for variations in clinical populations and practice settings. Despite recognition of this problem, there is no formal mechanism for assessing what the need is for flexibility in guidelines, or for deciding how to incorporate such flexibility into recommendations. OBJECTIVE: This research sought to provide a formal basis to determine when clinical circumstances vary sufficiently that guideline recommendations should differ, how recommendations should be tailored for a specific clinical setting, and whether the benefit associated with such site-specific guidelines justifies the expense of their development. RESULTS: The authors describe an approach for estimating the maximum health benefit that developers can obtain by eliminating uncertainty about differences in the patient populations and practice settings in which a guideline will be used. This estimate, the expected value of customization, provides a mechanism to evaluate the cost-effectiveness of the development of site-specific guidelines that account explicitly for variation in clinical circumstances. Application of this method to the development of screening guidelines for human immunodeficiency virus (HIV) infection indicates that the development of site-specific guidelines potentially is cost-effective. Site-specific guidelines either improve, or leave unchanged, the efficiency of HIV screening; whether they increase or decrease total expenditures and health benefits depends on the choice of a cost-effectiveness threshold, and the clinical problem. CONCLUSIONS: Development of guideline recommendations based on decision models provides a normative approach for evaluating the need for and the cost-effectiveness of site-specific guidelines that have been tailored to specific practice settings. Such site-specific guidelines can improve substantially the expected health benefit and the economic efficiency of practice guidelines.

An analysis of optimal resource allocation for prevention of infection with human immunodeficiency virus (HIV) in injection drug users and non-users.

Millions of dollars are spent annually to prevent infection with human immunodeficiency virus (HIV) without a thorough understanding of the most effective way to allocate these resources. The authors' objective was to determine the allocation of new resources among prevention programs targeted to a population of injection drug users (IDUs) and a population of non-injection drug users (non-IDUs) that would minimize the total number of incident cases of HIV infection over a given time horizon. They developed a dynamic model of HIV transmission in IDUs and non-IDUs and estimated the relationship between prevention program expenditures and reductions in HIV transmission. They evaluated three prevention programs: HIV testing with routine counseling, HIV testing with intensive counseling, and HIV testing and counseling linked to methadone maintenance programs. They modeled a low-risk IDU population (5% HIV prevalence) and a moderate-risk IDU population (10% HIV prevalence). For different available budgets, they determined the allocation of resources among the prevention programs and populations that would minimize the number of new cases of HIV infection over a five-year period, as well as the incremental value of additional prevention funds. The study framework provides a quantitative, systematic approach to funding programs to prevent HIV infection that accounts for HIV transmission dynamics, population size, and the costs and effectiveness of the interventions in reducing HIV transmission. The approach is general and can be used to evaluate a broader group of prevention programs and risk populations. This framework thus could enable policy makers and clinicians to identify a portfolio of programs that provide, collectively, the most benefit for a given budget.

Threshold analysis using diagnostic tests with multiple results.

Clinical problems represented by decision trees can be analyzed in terms of the probability threshold model, which provides management recommendations based on the prior probability of disease, the test threshold, and the test-treatment threshold. As originally proposed, the threshold model assumes that diagnostic tests provide information about a single event that is relevant to the decision. For some problems, however, a diagnostic test may provide information about more than one such event (e.g., a computed tomography [CT] scan gives information about both mediastinal and hilar metastases in lung cancer). The authors extend the probability threshold model to cases in which a single test provides information about two events that are relevant to the decision. They derive four thresholds that determine the best strategy for any combination of test results. The approach is illustrated for the decision to use a CT scan to stage lung cancer. The analysis reveals that: 1) the range of prior probabilities for which testing is optimal increases; 2) for some prior probabilities only test results about one event are important; 3) for some prior probabilities test results about both events are important; and 4) failure to account fully for information provided by a test can lead to erroneous test and treatment recommendations.

Representation and analysis of medical decision problems with influence diagrams.

Influence diagrams are a powerful graphic representation for decision models, complementary to decision trees. Influence diagrams and decision trees are different graphic representations for the same underlying mathematical model and operations. This article describes the elements of an influence diagram, and shows several familiar decision problems represented as decision trees and as influence diagrams. The authors also contrast the information highlighted in each graphic representation, demonstrate how to calculate the expected utilities of decision alternatives modeled with an influence diagram, provide an overview of the conceptual basis of the solution algorithms that have been developed for influence diagrams, discuss the strengths and limitations of influence diagrams relative to decision trees, and describe the mathematical operations that are used to evaluate both decision trees and influence diagrams. They use clinical examples to illustrate the mathematical operations of the influence-diagram-evaluation algorithm; these operations are arc reversal, chance node removal by averaging, and decision node removal by policy determination. Influence diagrams may be helpful when problems have a high degree of conditional independence, when large models are needed, when communication of the probabilistic relationships is important, or when the analysis requires extensive Bayesian updating. The choice of graphic representation should be governed by convenience, and will depend on the problem being analyzed, on the experience of the analyst, and on the background of the consumers of the analysis.