Medical Decision Making recent issues

Using the Principles of Randomized Controlled Trial Design to Guide Test Evaluation

Lord, S. J., Irwig, L., Bossuyt, P. M. M. — Thu, 12 Nov 2009 10:52:04 PST

The decision to use a new test should be based on evidence that it will improve patient outcomes or produce other benefits without adversely affecting patients. In principle, long-term randomized controlled trials (RCTs) of test-plus-treatment strategies offer ideal evidence of the benefits of introducing a new test relative to current best practice. However, long-term RCTs may not always be necessary. The authors advocate using the hypothetical RCT as a conceptual framework to identify what types of comparative evidence are needed for test evaluation. Evaluation begins by stating the major claims for the new test and determining whether it will be used as a replacement, add-on, or triage test to achieve these claims. A flow diagram of this hypothetical RCT is constructed to show the essential design elements, including population, prior tests, new test and existing test strategies, and primary and secondary outcomes. Critical steps in the pathway between testing and patient outcomes, such as differences in test accuracy, changes in treatment, or avoidance of other tests, are displayed for each test strategy. All differences between the tests at these critical steps are identified and prioritized to determine the most important questions for evaluation. Long-term RCTs will not be necessary if it is valid to use other sources of evidence to address these questions. Validity will depend on issues such as the spectrum of patients identified by the old and new test strategies.

Proposals for a Phased Evaluation of Medical Tests

Lijmer, J. G., Leeflang, M., Bossuyt, P. M. M. — Thu, 12 Nov 2009 10:52:04 PST

Background. In drug development, a 4-phase hierarchical model for the clinical evaluation of new pharmaceuticals is well known. Several comparable phased evaluation schemes have been proposed for medical tests. Purpose. To perform a systematic search of the literature, a synthesis, and a critical review of phased evaluation schemes for medical tests. Data Sources. Literature databases of Medline, Web of Science, and Embase. Study Selection and Data Extraction. Two authors separately evaluated potentially eligible papers and independently extracted data. Results. We identified 19 schemes, published between 1978 and 2007. Despite their variability, these models show substantial similarity. Common phases are evaluations of technical efficacy, diagnostic accuracy, diagnostic thinking efficacy, therapeutic efficacy, patient outcome, and societal aspects. Conclusions. The evaluation frameworks can be useful to distinguish between study types, but they cannot be seen as a necessary sequence of evaluations. The evaluation of tests is most likely not a linear but a cyclic and repetitive process.

Decision-Analytic Modeling to Evaluate Benefits and Harms of Medical Tests: Uses and Limitations

Trikalinos, T. A., Siebert, U., Lau, J. — Thu, 12 Nov 2009 10:52:04 PST

The clinical utility of medical tests is measured by whether the information they provide affects patient-relevant outcomes. To a large extent, effects of medical tests are indirect in nature. In principle, a test result affects patient outcomes mainly by influencing treatment choices. This indirectness in the link between testing and its downstream effects poses practical challenges to comparing alternate test-and-treat strategies in clinical trials. Keeping in mind the broader audience of researchers who perform comparative effectiveness reviews and technology assessments, the authors summarize the rationale for and pitfalls of decision modeling in the comparative evaluation of medical tests by virtue of specific examples. Modeling facilitates the interpretation of test performance measures by connecting the link between testing and patient outcomes, accounting for uncertainties and explicating assumptions, and allowing the systematic study of tradeoffs and uncertainty. The authors discuss challenges encountered when modeling test-and-treat strategies, including but not limited to scarcity of data on important parameters, transferring estimates of test performance across studies, choosing modeling outcomes, and obtaining summary estimates for test performance data.

Additional Patient Outcomes and Pathways in Evaluations of Testing

Bossuyt, P. M. M., McCaffery, K. — Thu, 12 Nov 2009 10:52:04 PST

Before medical tests are introduced into practice, they should be properly evaluated. Randomized trials and other comprehensive evaluations of tests and test strategies can best be designed based on an understanding of how tests can benefit or harm patients. Tests primarily affect patients’ health by guiding clinical decision making and downstream management, such as the decision to order more tests or to start, stop, or modify treatment. In this article, the authors demonstrate that tests can have additional effects on patient outcome, which may be cognitive, emotional, social, or behavioral. They present a framework to help researchers and policy makers consider the cognitive, emotional, social, and behavioral effects of testing. These additional effects may be important themselves and may also influence the clinical outcomes of testing through different pathways. The authors provide examples from test evaluations in the literature to illustrate how these additional effects can be important in the evaluation of testing or indeed any health intervention.

Effects of Categorizing Continuous Variables in Decision-Analytic Models

Bentley, T. G. K., Weinstein, M. C., Kuntz, K. M. — Thu, 12 Nov 2009 10:52:04 PST

Purpose. When using continuous predictor variables in discrete-state Markov modeling, it is necessary to create categories of risk and assume homogeneous disease risk within categories, which may bias model outcomes. This analysis assessed the tradeoffs between model bias and complexity and/or data limitations when categorizing continuous risk factors in Markov models. Methods. The authors developed a generic Markov cohort model of disease, defining bias as the percentage change in life expectancy gain from a hypothetical intervention when using 2 to 15 risk factor categories as compared with modeling the risk factor as a continuous variable. They evaluated the magnitude and sign of bias as a function of disease incidence, disease-specific mortality, and relative difference in risk among categories. Results. Bias was positive in the base case, indicating that categorization overestimated life expectancy gains. The bias approached zero as the number of risk factor categories increased and did not exceed 4% for any parameter combinations or numbers of categories considered. For any given disease-specific mortality and disease incidence, bias increased with relative risk of disease. For any given relative risk, the relationship between bias and parameters such as disease-specific mortality or disease incidence was not always monotonic. Conclusions. Under the assumption of a normally distributed risk factor and reasonable assumption regarding disease risk and moderate values for the relative risk of disease given risk factor category, categorizing continuously valued risk factors in Markov models is associated with less than 4% absolute bias when at least 2 categories are used.

Incorporating Herd Immunity Effects into Cohort Models of Vaccine Cost-Effectiveness

Bauch, C. T., Anonychuk, A. M., Van Effelterre, T., Pham, B. Z., Merid, M. F. — Thu, 12 Nov 2009 10:52:04 PST

Background. Cohort models are often used in cost-effectiveness analysis (CEA) of vaccination. However, because they cannot capture herd immunity effects, cohort models underestimate the reduction in incidence caused by vaccination. Dynamic models capture herd immunity effects but are often not adopted in vaccine CEA. Objective. The objective was to develop a pseudo-dynamic approximation that can be incorporated into an existing cohort model to capture herd immunity effects. Methods. The authors approximated changing force of infection due to universal vaccination for a pediatric infectious disease. The projected lifetime cases in a cohort were compared under 1) a cohort model, 2) a cohort model with pseudo-dynamic approximation, and 3) an age-structured susceptible-exposed-infectious-recovered compartmental (dynamic) model. The authors extended the methodology to sexually transmitted infections. Results. For average to high values of vaccine coverage (P > 60%) and small to average values of the basic reproduction number (R₀ < 10), which describes school-based vaccination programs for many common infections, the pseudo-dynamic approximation significantly improved projected lifetime cases and was close to projections of the full dynamic model. For large values of R₀ (R₀ > 15), projected lifetime cases were similar under the dynamic model and the cohort model, both with and without pseudo-dynamic approximation. The approximation captures changes in the mean age at infection in the 1st vaccinated cohort. Conclusions. This methodology allows for preliminary assessment of herd immunity effects on CEA of universal vaccination for pediatric infectious diseases. The method requires simple adjustments to an existing cohort model and less data than a full dynamic model.

Planning Posttherapeutic Oncology Surveillance Visits Based on Individual Risk

Filleron, T., Barrett, A., Ataman, O., Kramar, A. — Thu, 12 Nov 2009 10:52:04 PST

The main objective of posttherapeutic surveillance in oncology is to detect recurrent disease associated with treatment failure. Current follow-up schedules are easy to apply because they are planned on a regular basis (for instance, every 3 months) but do not take into account prognostic factors associated with time to failure. We propose a 2-stage strategy to individualize surveillance by first identifying prognostic factors for time to failure, then modeling cumulative risk or cumulative incidence to plan visits according to equal quantiles of risk or probability of failure, respectively. Using data from a clinical trial of radiotherapy in non—small cell lung cancer patients, we demonstrate how this method could improve the early detection of relapse.

Incorporating Extrinsic Goals Into Decision and Cost-Effectiveness Analyses

Hazen, G. B., Schwartz, A. — Thu, 12 Nov 2009 10:52:04 PST

It has not been widely recognized that medical patients as individuals may have goals that are not easily expressed in terms of quality-adjusted life years (QALYs). The QALY model deals with ongoing goals such as reducing pain or maintaining mobility, but goals such as completing an important project or seeing a child graduate from college occur at unique points in time and do not lend themselves to easy expression in terms of QALYs. Such extrinsic goals have been posited as explanations for preferences inconsistent with the QALY model, such as unwillingness to trade away time or accept gambles. In this article, the authors examine methods for including extrinsic goals in medical decision and cost-effectiveness analyses. As illustrations, they revisit 2 previously published analyses, the management of unruptured intracranial arteriovenous malformations (AVMs) and the evaluation of preventive strategies for BRCA + women.

Development of Goal-Sensitive Health-Related Utility Assessment Procedures

Schwartz, A., Hazen, G. B., Leifer, A., Heckerling, P. S. — Thu, 12 Nov 2009 10:52:04 PST

Purpose. To measure the degree to which people express willingness to trade life or health for nonmedical goals. Method. In 3 studies, outpatients provided important life goals. In study 1, patients performed time-tradeoff between life-years and goal achievement and chose between states that varied in goal achievement, life expectancy, and disability; in study 2, patients made choices that traded off health state and goal achievement; in study 3, patients performed time-tradeoff assessments in 3 different goal achievement contexts. Results. In study 1 (n = 58), participants were eager to trade life-years for goal achievement, trading, on average, 71% of their remaining life for certain achievement v. certain nonachievement or 54% of their remaining life for their expected likelihood of achievement v. nonachievement. Life expectancy, disability status, and goal achievement each had a significant main effect on utility. In study 2 (n = 54), participants equally preferred a moderately impaired health state with goal achievement to perfect health without goal achievement and more strongly preferred the moderately impaired state with goal achievement than other less impaired states without goal achievement. Study 3 (n = 62) demonstrated that the mere discussion of goals and goal achievement or nonachievement in the context of a standard time-tradeoff assessment (without trading off goals) did not impact the assessment. Conclusions. Nonmedical life goals are important determinants of quality of life. People express willingness to trade off life and health in pursuit of these goals, which are extrinsic to the standard quality-adjusted life-year model.

The Influence of Treatment Effect Size on Willingness to Adopt a Therapy

Aberegg, S. K., O'Brien, J. M., Khoury, P., Patel, R., Arkes, H. R. — Thu, 12 Nov 2009 10:52:04 PST

Background. Physicians are slow to adopt novel therapies, and the reasons for this are poorly understood. The authors sought to determine if the size of the treatment effect of a novel therapy influences willingness to adopt it. Methods. We developed 2 experimental vignette pairs describing a trial of a therapy for a hypothetical disease that showed a statistically significant mortality benefit. The size of the mortality effect was varied in vignettes of a pair (3% v. 10%). The 2 experimental vignette pairs differed in whether study enrollment was reported. Vignettes were mailed to a random sample of physicians using an intersubject design. The main study outcome was respondents’ willingness to adopt the hypothetical therapy, based on the results of the hypothetical trial. Results. There were 124 and 89 respondents to vignette pairs 1 and 2, respectively. In vignette pair 1, 91% versus 71% of respondents adopted the therapy when it reduced mortality by 10% and 3%, respectively (P = 0.0058). For vignette pair 2, 88% versus 51% of respondents adopted the therapy when it reduced mortality by 10% and 3%, respectively (P = 0.0002). In both vignette pairs, nonadopters were more likely than adopters to report side effects of the therapy as a principal reason for their decision. Conclusions. In this study, respondents were less likely to adopt a lifesaving therapy if its associated mortality reduction was 3% compared to 10%. Because most therapies for major medical conditions reduce mortality within or below this range, and because there were no opportunity costs associated with the adoption of the therapy, we believe that this effect represents a bias. Further investigation will be required to determine its prevalence and mechanism.

Diagnostic Certainty as a Source of Medical Practice Variation in Coronary Heart Disease: Results from a Cross-National Experiment of Clinical Decision Making

Thu, 12 Nov 2009 10:52:04 PST

The authors examined physician diagnostic certainty as one reason for cross-national medical practice variation. Data are from a factorial experiment conducted in the United States, the United Kingdom, and Germany, estimating 384 generalist physicians’ diagnostic and treatment decisions for videotaped vignettes of actor patients depicting a presentation consistent with coronary heart disease (CHD). Despite identical vignette presentations, the authors observed significant differences across health care systems, with US physicians being the most certain and German physicians the least certain (P < 0.0001). Physicians were least certain of a CHD diagnoses when patients were younger and female (P < 0.0086), and there was additional variation by health care system (as represented by country) depending on patient age (P < 0.0100) and race (P < 0.0021). Certainty was positively correlated with several clinical actions, including test ordering, prescriptions, referrals to specialists, and time to follow-up.

The German Coronary Artery Disease Risk Screening Model: Development, Validation, and Application of a Decision-Analytic Model for Coronary Artery Disease Prevention with Statins

Stollenwerk, B., Gerber, A., Lauterbach, K. W., Siebert, U. — Thu, 12 Nov 2009 10:52:04 PST

Background. Coronary artery disease (CAD) is a major cause of death in industrial countries, leading to high health-related costs and decreased quality of life. Objective. To develop and validate a decision-analytic model for CAD risk screening in Germany (German Coronary Artery Disease Screening Model). Design. Markov model. Target Population. Age- and gender-specific cohorts of the German population. Data Sources. Mortality rates posted by the German Federal Statistical Office, the German Health Survey, social health insurance institutions, the MONICA Augsburg study, and the literature. Time Horizon. Lifetime. Interventions. CAD risk screening for high-risk individuals using Framingham risk equation and use of statins as the primary preventive measure, compared with a setting without screening. Outcome Measures. Life-years (LY) gained, quality-adjusted life-years (QALYs) gained. Results. The model-based CAD incidence corresponds well with empirical data from the MONICA Augsburg study. Health outcomes depend on the screening threshold (cutoff value of Framingham 10-year risk) and on the age and gender of the cohort screened (0.03 to 0.26 LYs and 0.06 to 0.42 QALYs gained per person screened in cohorts of 50- and 60-year-old men and women, respectively). Conclusions. The model provides a valid tool for evaluating the long-term effectiveness of CAD risk screening in Germany. Using statins as a primary prevention intervention for CAD in high-risk individuals identified by screening could improve the long-term health of the German population.

Web Exclusive White Paper Series on Diagnostic Test Evaluation

Helfand, M. — Thu, 12 Nov 2009 10:52:04 PST

Getting Down to Details in the Design and Use of Decision Aids

Fagerlin, A. — Fri, 24 Jul 2009 15:07:57 PDT

Modeling Bioterrorism and Disaster Preparedness: SMDM's Recommendations for Design and Reporting

Sanders, G. D. — Fri, 24 Jul 2009 15:07:57 PDT

Evaluating the Capability and Cost of a Mass Influenza and Pneumococcal Vaccination Clinic via Computer Simulation

Washington, M. L. — Fri, 24 Jul 2009 15:07:57 PDT

Objective. To determine if a mass influenza/pneumococcal vaccination clinic could vaccinate 15,000 clients in 17 h; optimize personnel configuration to maximize number of clients vaccinated; and estimate costs (opportunity and clinic) and revenue. Method. The author used a discrete event simulation model to estimate the throughput of the vaccination clinic as the number of clients (arrival intensity) increased and as staff members were reassigned to different workflows. We represented workflows for 3 client types: ``Medicare,'' ``Special,'' and ``Cash,'' where ``Special'' designates Medicare clients who needed assistance moving through the clinic. The costs of supplies, staff sal-aries, and client waiting time were included in the model. We compared the ``original'' model based on the staffing and performance of an actual clinic to an ``optimized'' model in which staff were reassigned to optimize number of clients vaccinated. Results. A maximum of 13,138 and 15,094 clients in the original and optimized models, respectively, were vaccinated. At the original arrival rate (8300 clients vaccinated in 17 h), supplies cost about $191,000 and were the most expensive component of the clinic operation in both models. However, as the arrival intensity increased to 140%, the ``Medicare'' client opportunity cost increased from $23,887 and $21,474 to $743,510 and $740,760 for the simulated original and optimized models, respectively. Conclusion. The clinic could reach their target of 15,000 vaccinees with 2 fewer staff members by rearranging staff assignments from ``Special'' to ``Medicare'' and ``Cash'' stations. Computer simulation can help public health officials determine the most efficient use of staff, machinery, supplies, and time.

Predicting Hospital Surge after a Large-Scale Anthrax Attack: A Model-Based Analysis of CDC's Cities Readiness Initiative Prophylaxis Recommendations

Hupert, N., Wattson, D., Cuomo, J., Hollingsworth, E., Neukermans, K., Xiong, W. — Fri, 24 Jul 2009 15:07:57 PDT

Background . After a major bioterrorism attack, the US Centers for Disease Control and Prevention (CDC) Cities Readiness Initiative (CRI) calls for dispensing of medical countermeasures to targeted populations within 48 hours. The authors explore how meeting or missing this 48-hour goal after a hypothetical aerosol anthrax attack would affect hospital surge, in light of the multiple uncertainties surrounding anthrax-related illness and response. Design . The authors created a discrete-time state transition computer model representing the dynamic interaction between disease progression of inhalational anthrax and the rate of dispensing of prophylactic antibiotics in an exposed population. Results. A CRI-compliant prophylaxis campaign starting 2 days after exposure would protect from 86% to 87% of exposed individuals from illness (assuming, in the base case, 90% antibiotic effectiveness and a 95% attack rate). Each additional day needed to complete the campaign would result in, on average, 2.4% to 2.9% more hospitalizations in the exposed population; each additional day's delay to initiating prophylaxis beyond 2 days would result in 5.2% to 6.5% additional hospitalizations. These population protection estimates vary roughly proportionally to antibiotic effectiveness but are relatively insensitive to variations in anthrax incubation period. Conclusion. Delays in detecting and initiating response to large-scale, covert aerosol anthrax releases in a major city would render even highly effective CRI-compliant mass prophylaxis campaigns unable to prevent unsustainable levels of surge hospitalizations. Although outcomes may improve with more rapid epidemiological identification of affected subpopulations and increased collaboration across regional public health and hospital systems, these findings support an increased focus on prevention of this public health threat.

Recommendations for Modeling Disaster Responses in Public Health and Medicine: A Position Paper of the Society for Medical Decision Making

Brandeau, M. L., McCoy, J. H., Hupert, N., Holty, J.-E., Bravata, D. M. — Fri, 24 Jul 2009 15:07:57 PDT

Purpose. Mathematical and simulation models are increasingly used to plan for and evaluate health sector responses to disasters, yet no clear consensus exists regarding best practices for the design, conduct, and reporting of such models. The authors examined a large selection of published health sector disaster response models to generate a set of best practice guidelines for such models. Methods. The authors reviewed a spectrum of published disaster response models addressing public health or health care delivery, focusing in particular on the type of disaster and response decisions considered, decision makers targeted, choice of outcomes evaluated, modeling methodology, and reporting format. They developed initial recommendations for best practices for creating and reporting such models and refined these guidelines after soliciting feedback from response modeling experts and from members of the Society for Medical Decision Making. Results. The authors propose 6 recommendations for model construction and reporting, inspired by the most exemplary models: health sector disaster response models should address real-world problems, be designed for maximum usability by response planners, strike the appropriate balance between simplicity and complexity, include appropriate outcomes that extend beyond those considered in traditional cost-effectiveness analyses, and be designed to evaluate the many uncertainties inherent in disaster response. Finally, good model reporting is particularly critical for disaster response models. Conclusions. Quantitative models are critical tools for planning effective health sector responses to disasters. The proposed recommendations can increase the applicability and interpretability of future models, thereby improving strategic, tactical, and operational aspects of preparedness planning and response.

Long-Term Health Outcomes of a Decision Aid: Data from a Randomized Trial of Adjuvant! in Women with Localized Breast Cancer

Vickers, A. J., Elkin, E. B., Peele, P. B., Dickler, M., Siminoff, L. A. — Fri, 24 Jul 2009 15:07:57 PDT

Purpose . Women with localized breast cancer face difficult decisions about adjuvant therapy. Several decision aids are available to help women choose between treatment options. Decision aids are known to affect treatment choices and may therefore affect patient survival. The authors aimed to model the effects of the Adjuvant! decision aid on expected survival in women with early stage breast cancer. Patients and Methods. Data were obtained from a randomized trial of Adjuvant! (n = 395). To calculate the effects of the decision aid on survival, the authors used the Adjuvant! survival predictions as a surrogate endpoint. Data from each arm were entered separately into statistical models to estimate change in survival associated with receiving the Adjuvant! decision aid. Results. Most women (~ 85%) chose a treatment option that maximized predicted survival. The effects of the decision aid on outcome could not be modeled because a small number of women (n = 12, 3%) chose treatment options associated with a large (5%—14%) loss in survival. These women—most typically estrogen receptor positive but refusing hormonal therapy—were equally divided between Adjuvant! and control groups and were not distinguished by medical or demographic factors. Conclusions. Expected benefit from treatment is a key variable in understanding patient behavior. A small number of women refuse adjuvant treatment associated with large increases in predicted survival, even when they are explicitly informed about the degree of benefit they would forgo. Investigation of the effects of decision aids on cancer survival is unlikely to be fruitful due to power considerations.

Should Clinicians Deliver Decision Aids? Further Exploration of the Statin Choice Randomized Trial Results

Fri, 24 Jul 2009 15:07:57 PDT

Background. Statin Choice is a decision aid about taking statins. The optimal mode of delivering Statin Choice (or any other decision aid) in clinical practice is unknown. Methods. To investigate the effect of mode of delivery on decision aid efficacy, the authors further explored the results of a concealed 2 x 2 factorial clustered randomized trial enrolling 21 endocrinologists and 98 diabetes patients and randomizing them to 1) receive either the decision aid or pamphlet about cholesterol, and 2) have these delivered either during the office visit (by the clinician) or before the visit (by a researcher). We estimated between-group differences and their 95% confidence intervals (CI) for acceptability of information delivery (1—7), knowledge about statins and coronary risk (0—9), and decisional conflict about statin use (0—100) assessed immediately after the visit. Follow-up was 99%. Results. The relative efficacy of the decision aid v. pamphlet interacted with the mode of delivery. Compared with the pamphlet, patients whose clinicians delivered the decision aid during the office visit showed significant improvements in knowledge (difference of 1.6 of 9 questions, CI 0.3, 2.8) and nonsignificant trends toward finding the decision aid more acceptable (odds ratio 3.1, CI 0.9, 11.2) and having less decisional conflict (difference of 7 of 100 points, CI -4, 18) than when a researcher delivered the decision aid just before the office visit. Conclusions. Delivery of decision aids by clinicians during the visit improves knowledge and shows a trend toward better acceptability and less decisional conflict.

Is There a Role for Decision Aids in Advanced Breast Cancer?

Sepucha, K. R., Ozanne, E. M., Partridge, A. H., Moy, B. — Fri, 24 Jul 2009 15:07:57 PDT

Background . A diagnosis of metastatic breast cancer (BC) forces patients and providers to make difficult treatment decisions. Objective. To pilot test a decision aid (DA) for advanced BC. Design . Pretest, posttest study. Setting. Two academic cancer centers in Boston, Massachusetts. Patients. Fifty patients diagnosed with advanced BC. Intervention. A patient DA that consisted of a 30-minute DVD and booklet. Measurements . Patients were surveyed at baseline, after the intervention, and at 3 months. Measures included use and acceptability of DA, distress, treatment goals, and preference for and actual participation in decisions. Physicians were surveyed at baseline and 3 months. Measures included treatment goals, assessment of patients' experience with treatments, and patients' preference for and actual participation in decisions. Results. Thirty-two patients (64%) enrolled and completed the baseline survey, 30 completed the postvideo survey, and 25 completed the 3-month survey. The DA was acceptable and did not increase distress. The majority desired to share decision making with their doctor. Only 38% achieved their desired level of participation. At baseline, agreement between patients and providers on the main goal of treatment (lengthen life v. relieve symptoms) was 50% ( = —0.045, P = 0.71), and at 3 months it was 74% ( = 0.125, P = 0.48). Conclusions. It is feasible to perform a clinical trial of a DA with advanced BC patients. Most participants wanted to participate in decisions about their care and found the DA acceptable. This study highlights several issues in developing and implementing DAs in this vulnerable population facing complex decisions.

Effect of Risk Communication Formats on Risk Perception Depending on Numeracy

Keller, C., Siegrist, M. — Fri, 24 Jul 2009 15:07:57 PDT

Objective. To examine the influence of numeracy on interpreting various risk communication formats. Design. A random sample of women (N = 266) completed a questionnaire assessing numeracy and risk perception of prenatal test results and results of colon cancer screening tests. The authors examined the relationships between risk level (high v. low) and format of risk presentation (ratio, pictogram, or Paling Perspective Scale) and whether these relationships differed based on the numeracy skills of the participant. Results. The authors identified a significant (P<0.001) 3-way interaction between format, risk level, and numeracy: high-numerate participants in the low-risk group perceived the test results as less risky compared with participants in the high-risk group (P < 0.001) with the Paling Perspective Scale but not with the other formats. For low-numerate participants, they did not observe differences between low- and high-risk scenarios for any of the 3 formats. The results were similar for the Down syndrome and colon cancer scenarios. Overall, the pictogram resulted in significantly lower risk ratings compared with the Paling Perspective Scale and the ratio with numerator 1 (P < 0.001). Conclusion. Different communication formats may produce different risk perceptions, but the effect is qualified by patients' numeracy skills.

A Fair Test of the Fair Innings?

Oliver, A. — Fri, 24 Jul 2009 15:07:57 PDT

Priority setting in health care under conventional rules of health economic evaluation is based upon the ethos of attempting to maximize post-treatment health gain given available health care resources. In his later years, Alan Williams advocated the ``fair innings argument,'' which balances differences in whole lifetime experiences of health with differences in post-treatment outcomes when prioritizing people for health care. This article reports a study that presented respondents with a number of abstract health care decision contexts in an attempt to test the extent to which post-treatment health maximization, the fair innings argument, or, indeed other ``decision rules,'' are evident in the respondents' answers. The results indicate that the most commonly observed decision rule differs substantially across health care contexts, and therefore imply that rather than pursue an overarching decision rule, it may be more appropriate to vary the rule according to the particular health care decision context under consideration.

The Half-Cycle Correction: Banish Rather Than Explain It

Barendregt, J. J. — Fri, 24 Jul 2009 15:07:57 PDT

The half-cycle correction is often used in discrete Markov models to estimate state membership. This article shows that the correction, in addition to being unintuitive, actually produces the wrong results in many circumstances. These include quality-adjusted life year (QALY) weights and unit costs that differ by cycle. The half-cycle correction is also incompatible with discounting of the obtained stream of state membership. It is furthermore shown that the life table method of estimating state membership obtains correct results under these circumstances and is also much more transparent. The article concludes that the half-cycle correction should be dropped in favor of the life table method.

The Incorporation of Income and Leisure in Health State Valuations When the Measure Is Silent: An Empirical Inquiry into the Sound of Silence

Brouwer, W. B. F., Grootenboer, S., Sendi, P. — Fri, 24 Jul 2009 15:07:58 PDT

Objective . The objective of the present study is to evaluate whether people 1) expect income and leisure to be affected by certain health states, 2) include the effects of ill-health on income and leisure in health state valuations when the measure is silent on both, and 3) what effect this has on these valuations. Data and Methods. A convenience sample of 75 individuals from the general public rated 3 different health states on a visual analogue scale without instruction on the incorporation of income and leisure. Different subgroups were created on the basis of expecting income and leisure to be affected and the indicated incorporation of these effects. Comparative and multivariate analyses were used to analyze the data. Results . The results show that most respondents (69%) did not consider income effects, whereas 61% did consider the effects on leisure. The expected influence of health states on income and leisure differed substantially between respondents. Only the incorporation of leisure proved to be influential in health state valuations. Conclusions. Health state valuation methods that are silent and noninformative regarding leisure and income lead to interrespondent differences regarding how they expect leisure and income to be affected and regarding the inclusion of these effects. This may be especially problematic for leisure if productivity costs are captured at the cost side of the cost-effectiveness ratio.

Construction of Health Preferences: A Comparison of Direct Value Assessment and Personal Narratives

Kerstholt, J. H., van der Zwaard, F., Bart, H., Cremers, A. — Fri, 24 Jul 2009 15:07:58 PDT

Background. Most terminally ill patients prefer to die at home rather than at an institution. However, patients are often insufficiently aware of the downsides of staying at home, which signals a need for effective decision aids. Objectives. The main purpose of the present study was to compare indirect methods of value elicitation (personal narratives [``stories''] in text or video) with a direct method (assessment of the subjective importance of each attribute). Methods. The authors asked 183 participants to evaluate 3 possible places to die: home, hospice, and nursing home. The participants received 1 of 3 value elicitation methods. The main dependent variable was participants' evaluations of the choice options before and after value elicitation, measured on a 100-point scale. Results . A shift occurred between pre- and posttest, F(4, 342) = 4.11, P = 0.003, only with the indirect methods. When text and videos were used, participants became more positive about a hospice (text: 41.9 to 49.1; video: 52.9 to 60.3). In the video condition, participants also became more positive about a nursing home (from 20.9 to 24.9). Conclusion . Stories have more impact in shaping people's preferences than merely asking for an assessment of attribute importance. The most straightforward explanation for this effect is that stories, particularly when presented in video, provide a better image of potential consequences.

Offering Chemotherapy and Hospice Jointly: One Solution to Hospice Underuse

Salz, T., Brewer, N. T. — Fri, 24 Jul 2009 15:07:58 PDT

Purpose . Patients with advanced lung cancer typically receive chemotherapy at the cost of receiving care that may promote quality of life more effectively. The authors examined whether offering chemotherapy and hospice concurrently, a clinically appropriate but often unavailable option, might resolve this problem. Method. Adult smokers (N = 198) completed an Internet-based survey in which they imagined having advanced lung cancer. Participants rated the effectiveness of 4 treatments (supportive care alone, chemotherapy with supportive care, hospice, and chemotherapy with hospice) at achieving 4 goals of treatment (extending survival, controlling symptoms, avoiding side effects, and promoting quality of life at the end of life). Results. Reflecting utilization patterns of lung cancer patients, few respondents preferred supportive care alone (10%) or hospice (19%), and many preferred chemotherapy (29%). The most common choice was concurrent chemotherapy and hospice (42%). Treatments that involved chemotherapy were seen as the most effective at extending survival, whereas treatments that involved hospice were seen as most effective at promoting quality of life. Effectiveness ratings were weakly related to preferences for hospice, moderately related to preferences for chemotherapy with supportive care, and strongly related to preferences for chemotherapy and hospice together. Conclusions. These findings suggest that interest in hospice may be low because, offered without chemotherapy, hospice is perceived as ineffective at controlling symptoms and avoiding side effects. Chemotherapy and hospice together may be a preferred option for treating advanced lung cancer. Furthermore, preferences for chemotherapy and hospice together best reflect the values people placed on the goals of treatment.

Quantitative Risk Stratification in Markov Chains with Limiting Conditional Distributions

Chan, D. C., Pollett, P. K., Weinstein, M. C. — Fri, 24 Jul 2009 15:07:58 PDT

Background . Many clinical decisions require patient risk stratification. The authors introduce the concept of limiting conditional distributions, which describe the equilibrium proportion of surviving patients occupying each disease state in a Markov chain with death. Such distributions can quantitatively describe risk stratification. Methods. The authors first establish conditions for the existence of a positive limiting conditional distribution in a general Markov chain and describe a framework for risk stratification using the limiting conditional distribution. They then apply their framework to a clinical example of a treatment indicated for high-risk patients, first to infer the risk of patients selected for treatment in clinical trials and then to predict the outcomes of expanding treatment to other populations of risk. Results. For the general chain, a positive limiting conditional distribution exists only if patients in the earliest state have the lowest combined risk of progression or death. The authors show that in their general framework, outcomes and population risk are interchangeable. For the clinical example, they estimate that previous clinical trials have selected the upper quintile of patient risk for this treatment, but they also show that expanded treatment would weakly dominate this degree of targeted treatment, and universal treatment may be cost-effective. Conclusions . Limiting conditional distributions exist in most Markov models of progressive diseases and are well suited to represent risk stratification quantitatively. This framework can characterize patient risk in clinical trials and predict outcomes for other populations of risk.

Errata

Fri, 24 Jul 2009 15:07:58 PDT

How Far Do You Go? Efficient Searching for Indirect Evidence

Hawkins, N., Scott, D. A., Woods, B. — Mon, 08 Jun 2009 15:38:41 PDT

Background. Indirect evidence is particularly valuable in health care decision making when direct trial evidence comparing relevant treatments is absent or limited. Current approaches using a predetermined set of comparators in the search query may fail to identify all relevant indirect evidence. Purpose. To present a framework for the efficient design of search strategies for identifying clinical trials providing indirect evidence for a treatment comparison. Findings. The authors present 2 search strategies that differ from traditional search strategies in using a series of iterative searches to identify the set of relevant comparators. In both, the comparators included in each search are determined by the results of previous searches. For a given number of searches, the strategies presented will find all indirect comparisons that include a certain number of comparators linking the treatments of interest. Methods of estimating the value of indirect evidence via a given number of comparators linking the treatments of interest are presented, thus allowing the burden of additional searching to be traded off against the likely impact of finding more distant comparisons. A practical illustration of the search strategies in the context of informing a network meta-analysis of second-line treatments for non-small cell lung cancer is presented. Conclusions. The iterative strategies presented offer a means of identifying such evidence and allow the researcher to determine the optimal scope of the search by estimating the value of additional indirect evidence.

Missing Celiac Disease in Family Medicine: The Importance of Hypothesis Generation

Kostopoulou, O., Devereaux-Walsh, C., Delaney, B. C. — Mon, 08 Jun 2009 15:38:41 PDT

Purpose. Delays in diagnosing celiac disease average 13 years. We aimed to identify reasons for misdiagnosis in family medicine. Background. During a larger study on diagnosis, a scenario describing a 30-year-old female with 3-month abdominal pain, diarrhea, and microcytic anemia consistent with celiac disease was presented on a computer to 84 family physicians. Their information gathering and diagnoses were recorded. Fifty physicians misdiagnosed, and 38 of these took part in ``stimulated recall'': they were asked to recall their hypotheses and inferences step by step, aided by a record of their information gathering. They were unaware of the misdiagnosis. Analyses. Transcripts were analyzed to identify whether celiac disease was mentioned and how information was interpreted. Two raters independently assessed information interpretation against the published evidence ( = 0.85). Results. Physicians did not change their diagnoses during stimulated recall. Only 10 physicians mentioned celiac disease as a hypothesis (26%). ``Diarrhea'' and ``pain relief by defecation,'' consistent with both celiac disease and irritable bowel syndrome (IBS), were only linked to IBS. ``Absence of weight loss'' led to rejecting celiac disease, although weight loss is characteristic of advanced disease. A complete blood count was requested as a routine test and not specifically for celiac disease. Thus, the unexpected result of ``microcytic anemia,'' inconsistent with IBS, did not trigger the correct diagnosis. Conclusions. Most physicians never considered celiac disease. Information inconsistent with the favorite IBS diagnosis was overlooked. Reviewing the case did not prompt physicians to consider celiac disease, re-evaluate the evidence, or rethink the IBS diagnosis.

Estimating Preference-Based Health Utilities Index Mark 3 Utility Scores for Childhood Conditions in England and Scotland

Petrou, S., Kupek, E. — Mon, 08 Jun 2009 15:38:41 PDT

Background . A common feature of studies that have compiled lists or catalogues of preference-based health-related quality-of-life weights for inclusion within quality-adjusted life years (QALYs) is their focus upon adult populations. More generally, utility measurement in or on behalf of children has been constrained by a number of methodological concerns. Objective. To augment previous catalogues of preference-based health-related quality-of-life weights by estimating preference-based Health Utilities Index Mark 3 (HUI3) multiattribute utility scores associated with a wide range of childhood conditions. Methods. Data for 2236 children from the ``Disability Survey 2000: Survey of Young People With a Disability and Sport'' formed the basis of this investigation. Ordinary least squares (OLS), Tobit, and censored least absolute deviations (CLAD) regression methods were used to estimate adjusted marginal disutilities for each condition from 2 thresholds: 1) a threshold of 1.0 representing perfect health and 2) a normative childhood utility threshold. Results. Prespecified statistical tests indicated a preference for the OLS regression model over the Tobit and CLAD models. The unadjusted mean, median, 25th percentile and 75th percentile HUI3 multiattribute utility scores and adjusted marginal disutilities are presented for 43 conditions. Notably, based on the OLS estimator, the adjusted marginal disutilities for hydrocephalus; learning and physical disabilities; other syndromes and associations; meningitis, encephalitis, and other infections of the central nervous system; and microcephaly were estimated at —0.889 (95% confidence interval [CI]: —0.727, —1.000), —0.858 (95% CI: —0.727, —0.989), —0.838 (95% CI: —0.668, —1.000), —0.826 (95% CI: —0.677, —0.975), and —0.820 (95% CI: —0.670, —0.970), respectively, when a perfect health threshold was applied, and —0.814 (95% CI: —0.656, —0.979), —0.783 (95% CI: —0.656, —0.918), —0.763 (95% CI: —0.597, —0.937), —0.751 (95% CI: —0.606, —0.904), and —0.745 (95% CI: —0.598, —0.899), respectively, when a normative childhood utility threshold was applied. Conclusion . Our estimates and their associated distributions can be used for the purposes of QALY estimation by analysts conducting economic evaluations within the childhood context.

A Hybrid Cohort Individual Sampling Natural History Model of Age-Related Macular Degeneration: Assessing the Cost-Effectiveness of Screening Using Probabilistic Calibration

Karnon, J., Czoski-Murray, C., Smith, K. J., Brand, C. — Mon, 08 Jun 2009 15:38:41 PDT

Background. Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness. It is likely that treatment of AMD at earlier stages is more effective than later treatment; thus, screening for AMD should be considered. The aim of this study was to develop a natural history model of AMD to estimate the cost-effectiveness of screening. Methods. A hybrid cohort/individual sampling decision analytic model was developed. Primary data sets, expert elicitation, and data from the literature were used to populate the model. To incorporate joint parameter uncertainty, and to populate unobservable parameters, an innovative form of probabilistic calibration was applied to a range of output parameters. Results. In the reference case, annual screening from age 60 y is the most cost-effective option, although this is subject to high levels of uncertainty. Alternative, age-specific utility values show that screening is predicted to be less cost-effective, assuming interventions that reduce progression to wet AMD moderately improve the cost-effectiveness of screening, whereas the addition of anti—vascular endothelial growth factor therapy for juxtafoveal or subfoveal wet AMD lesions improves the cost-effectiveness of screening significantly. Conclusions. The extent of the uncertainty around the mean results, and the additional resources and possible reorganization of services required to implement screening, indicate that it may be preferable to reduce the level of uncertainty before implementing screening for AMD. Initial actions may be best targeted at assessing how routine data may be used to describe clinical presentation, a screening pilot study, and a secondary costing study.

Physicians' Anticipated Regret and Diagnostic Testing: Comment on Hozo and Djulbegovic, 2008

DeKay, M. L. — Mon, 08 Jun 2009 15:38:41 PDT

Will Insistence on Practicing Medicine According to Expected Utility Theory Lead to an Increase in Diagnostic Testing? Reply to DeKay's Commentary: Physicians' Anticipated Regret and Diagnostic Testing

Hozo, I., Djulbegovic, B. — Mon, 08 Jun 2009 15:38:41 PDT

Long-Term Cost-Effectiveness of Disease Management in Systolic Heart Failure

Miller, G., Randolph, S., Forkner, E., Smith, B., Galbreath, A. D. — Mon, 08 Jun 2009 15:38:41 PDT

Background. Although congestive heart failure (CHF) is a primary target for disease management programs, previous studies have generated mixed results regarding the effectiveness and cost savings of disease management when applied to CHF. Objective. We estimated the long-term impact of systolic heart failure disease management from the results of an 18-month clinical trial. Methods. We used data generated from the trial (starting population distributions, resource utilization, mortality rates, and transition probabilities) in a Markov model to project results of continuing the disease management program for the patients' lifetimes. Outputs included distribution of illness severity, mortality, resource consumption, and the cost of resources consumed. Both cost and effectiveness were discounted at a rate of 3% per year. Cost-effectiveness was computed as cost per quality-adjusted life year (QALY) gained. Results. Model results were validated against trial data and indicated that, over their lifetimes, patients experienced a lifespan extension of 51 days. Combined discounted lifetime program and medical costs were $4850 higher in the disease management group than the control group, but the program had a favorable long-term discounted cost-effectiveness of $43,650/QALY. These results are robust to assumptions regarding mortality rates, the impact of aging on the cost of care, the discount rate, utility values, and the targeted population. Conclusions. Estimation of the clinical benefits and financial burden of disease management can be enhanced by model-based analyses to project costs and effectiveness. Our results suggest that disease management of heart failure patients can be cost-effective over the long term.

Valuing Health: Does Enriching a Scenario Lead to Higher Utilities?

Peeters, Y., Stiggelbout, A. M. — Mon, 08 Jun 2009 15:38:41 PDT

Objectives . Patients have been found to value their own experienced health state higher than an investigator-constructed scenario of that health state. The aim of this study was to investigate if patients value their own experienced health state higher than a standard EQ-5D scenario of their health state and if ``enriching'' this scenario by adding individualized attributes reduces the differences between experienced health and the scenario. Methods . Face-to-face interviews were held with 129 patients with rheumatoid arthritis. Patients were asked to value in a time tradeoff their own experienced health; 6 standard EQ-5D scenarios, of which the 5th (untold to them) represented their own health state; and a standard EQ-5D scenario of their health state (identified as such) enriched with individual attributes. Results. The own experienced health state was not valued differently from the own standard EQ-5D state and was lower compared to the own enriched EQ-5D state of that same health state. An interaction effect was found for health status. Patients with better health did not report different values for their own experienced health compared with their own standard EQ-5D description; their own experienced state was rated lower than their own enriched EQ-5D description. Patients with poor health valued all 3 health states similarly. Surprisingly, utilities for scenarios enriched with exclusively negative individual attributes were not lower than those for the own standard EQ-5D description. Conclusion. The hypothesis that disparities in valuation can be attributed to EQ-5D description being too sparse was not confirmed.

Early Stopping Rules in Clinical Trials Based on Sequential Monitoring of Serious Adverse Events

Kramar, A., Bascoul-Mollevi, C. — Mon, 08 Jun 2009 15:38:41 PDT

Several multistage or group sequential statistical methods have been developed for defining stopping rules in terms of efficacy in phase II and III clinical trials, but they rely on interim analyses after the inclusion of a fixed number of patients. These methods, however, need to be adapted for the evaluation of serious adverse events (SAEs), which can occur relatively early in the trial. A high frequency of their occurrence may require the trial to close early. The methods developed here define stopping rules after the occurrence of each SAE by comparing the number of patients included to the number of patients satisfying maximum SAE criteria. The nominal type I error, power, and average sample number (ASN) under specific hypotheses are obtained through simulations. Data from a clinical trial are presented as an example.

Optimizing the Start Time of Statin Therapy for Patients with Diabetes

Denton, B. T., Kurt, M., Shah, N. D., Bryant, S. C., Smith, S. A. — Mon, 08 Jun 2009 15:38:41 PDT

Background . Clinicians often use validated risk models to guide treatment decisions for cardiovascular risk reduction. The most common risk models for predicting cardiovascular risk are the UKPDS, Framingham, and Archimedes models. In this article, the authors propose a model to optimize the selection of patients for statin therapy of hypercholesterolemia, for patients with type 2 diabetes, using each of the risk models. For each model, they evaluate the role of age, gender, and metabolic state on the optimal start time for statins. Method. Using clinical data from the Mayo Clinic electronic medical record, the authors construct a Markov decision process model with health states composed of cardiovascular events and metabolic factors such as total cholesterol and high-density lipoproteins. They use it to evaluate the optimal start time of statin treatment for different combinations of cardiovascular risk models and patient attributes. Results. The authors find that treatment decisions depend on the cardiovascular risk model used and the age, gender, and metabolic state of the patient. Using the UKPDS risk model to estimate the probability of coronary heart disease and stroke events, they find that all white male patients should eventually start statin therapy; however, using Framingham and Archimedes models in place of UKPDS, they find that for male patients at lower risk, it is never optimal to initiate statins. For white female patients, the authors also find some patients for whom it is never optimal to initiate statins. Assuming that age 40 is the earliest possible start time, the authors find that the earliest optimal start times for UKPDS, Framingham, and Archimedes are 50, 46, and 40, respectively, for women. For men, the earliest optimal start times are 40, 40, and 40, respectively. Conclusions. In addition to age, gender, and metabolic state, the choice of cardiovascular risk model influences the apparent optimal time for starting statins in patients with diabetes.

Natural Frequencies Help Older Adults and People with Low Numeracy to Evaluate Medical Screening Tests

Galesic, M., Gigerenzer, G., Straubinger, N. — Mon, 08 Jun 2009 15:38:41 PDT

Background. Understanding information about medical screening tests often requires estimating positive predictive values (i.e., posterior probabilities), which is a notoriously difficult task. Previous studies have shown that representation of information in terms of natural frequencies (i.e., counts of occurrences that preserve base rates) facilitates judgments of positive predictive values. The objective of this study was to investigate whether natural frequencies facilitate accurate estimates in elderly people and whether performance depends on numeracy skills. Elderly people are more often than younger people required to use such information to make informed choices regarding medical procedures (e.g., screenings). Method. This was an experimental study in which information about 2 medical screening tests was presented either as conditional probabilities or natural frequencies. Participants were 47 older adults (62—77 years of age; average numeracy score 8.6) and 115 younger adults (18—35 years of age; average numeracy score 10.3). Results. When the screening information was presented in terms of conditional probabilities, only 15% of the younger adults and 18% of the older adults provided accurate estimates in at least 1 of the tasks. When information was presented in terms of natural frequencies, 55% of the younger adults and 58% of the elderly participants gave correct estimates. This effect occurred without explicit training. Furthermore, participants with higher numeracy scores performed better in the estimation tasks than those with lower numeracy scores. Conclusions. Natural frequencies help elderly and young patients—including those with lower numeracy skills—to understand positive predictive values of medical screening tests.

The Effect of Erroneous Computer Interpretation of ECGs on Resident Decision Making

Southern, W. N., Arnsten, J. H. — Mon, 08 Jun 2009 15:38:41 PDT

Background . The use of computer interpretations of electrocardiograms (ECGs) as an aid to physician interpretations is widespread. Computer misinterpretations are common and negatively affect physician interpretations. Objective . To measure the effect of computer ECG misinterpretations on clinical decision making. Design. Quasi-randomized trial. Setting. Resident teaching conferences. Participants . Included 105 internal and emergency medicine residents. Intervention. After a brief case presentation, residents were asked to interpret an ECG and choose appropriate management. Residents chose from a concealed stack of handouts; some contained an erroneous computer interpretation of the ECG (citing acute ischemia), and some contained no computer interpretation. Measurements. ECG interpretations and management decisions by residents whose ECG did or did not include an erroneous computer interpretation were compared using chi-square tests. Results. The presence or absence of erroneous computer interpretations of ischemia did not significantly affect residents' ECG interpretations (P=0.62). However, the residents whose ECGs included erroneous computer interpretations were more likely to recommend revascularization than the residents without (30% v. 10%, P= 0.01). Of those residents who read the ECG as diagnostic of ischemia, those with the erroneous computer interpretation were more likely to recommend revascularization than those without (54% v. 25%, P=0.048). Limitations . A single ECG was used. Conclusions. Erroneous computer interpretations of ECGs affected residents' clinical decision making in the absence of an effect on the actual interpretation of the ECG. Measuring the impact of computer misinterpretations by examining only physician interpretations will underestimate the effect of computer misinterpretations on clinical decision making.

The Hippocratic Oath, Effect Size, and Utility Theory

Bordley, R. F. — Mon, 08 Jun 2009 15:38:41 PDT

To be consistent with the Hippocratic Oath, this article proposes that a physician choose that treatment that has the greatest chance of giving the patient an outcome no worse than the uncertain outcome an untreated patient would experience. As this article shows, this specifies the utility function that the physician should use in choosing among treatments. This utility function, although varying with the life circumstances of the patient, need not reflect the patient's utility function. This Hippocratic utility function can be estimated with an effect size measure similar to the stochastic superiority and common language effect size measures used in the statistical analysis of experiments.

Weighing Harm in Therapeutic Decisions of Smear-Negative Pulmonary Tuberculosis

Mon, 08 Jun 2009 15:38:41 PDT

Purpose. To relate the intuitive weight of harm by commission and harm by omission in therapeutic decisions for pulmonary tuberculosis, and to compare it with a weight based on probabilities. Methods. Clinicians were asked for an estimation of probabilities related with the outcome of treated and nontreated pulmonary tuberculosis and for the toll of wrong decisions. Three ratios of the weight of forgoing a treatment in false-negative patients against the weight of treating false-positives were calculated. The first was based on intuitive estimations, whereas the second and third were based on calculated, either through intuitive estimations of probabilities or through literature data. The association between experience and the difference between the intuitive and the calculated ratios was assessed. Results. Eighty-one participants from Ecuador, Laos, Nepal, and Rwanda responded. The ratio of intuitive weights was 2.0 (interquartile range [IQR], 1.0—4.0) and the ratio of calculated weights based on intuitive probabilities was 64 (IQR, 25.0—169.6; P < 0.001). The ratio of calculated weight based on literature probabilities was 30 (IQR, 17.9—59.2). No association (R² = 0.03) was found between experience and accuracy in estimating the weight of errors. Conclusion. The weight of a false negative is more important than the weight of a false positive for therapeutic decisions in pulmonary tuberculosis. The ratio of the intuitively estimated weights was much lower than the calculation based on intuitively estimated influencing factors. Clinicians were accurate in estimating probabilities but failed to incorporate them into therapeutic decisions.

Laypersons' Responses to the Communication of Uncertainty Regarding Cancer Risk Estimates

Mon, 08 Jun 2009 15:38:41 PDT

Objective . To explore laypersons' responses to the communication of uncertainty associated with individualized cancer risk estimates and to identify reasons for individual differences in these responses. Design. A qualitative study was conducted using focus groups. Participants were informed about a new colorectal cancer risk prediction model, and presented with hypothetical individualized risk estimates using presentation formats varying in expressed uncertainty (range v. point estimate). Semistructured interviews explored participants' responses to this information. Participants and Setting . Eight focus groups were conducted with 48 adults aged 50 to 74 residing in 2 major US metropolitan areas, Chicago, IL and Washington, DC. Purposive sampling was used to recruit participants with a high school or greater education, some familiarity with information technology, and no personal or immediate family history of cancer. Results . Participants identified several sources of uncertainty regarding cancer risk estimates, including missing data, limitations in accuracy and source credibility, and conflicting information. In comparing presentation formats, most participants reported greater worry and perceived risk with the range than with the point estimate, consistent with the phenomenon of ``ambiguity aversion.'' However, others reported the opposite effect or else indifference between formats. Reasons suggested by participants' responses included individual differences in optimism and motivations to reduce feelings of vulnerability and personal lack of control. Perceptions of source credibility and risk mutability emerged as potential mediating factors. Conclusions. Laypersons' responses to the communication of uncertainty regarding cancer risk estimates differ, and include both heightened and diminished risk perceptions. These differences may be attributable to personality, cognitive, and motivational factors.

Health Literacy and Cancer Risk Perception: Implications for Genomic Risk Communication

Fri, 10 Apr 2009 11:12:28 PDT

Background. As new genomic technology expands the number of medical tests available to physicians and patients, identifying gaps in our understanding of how best to communicate risk is increasingly important. We examined how health literacy informs breast cancer survivors' understanding of and meaning assigned to recurrence risks yielded by genomic tests. Methods. Study participants were posttreatment female breast cancer survivors (N =163) recruited at a university breast cancer clinic. We assessed their health literacy (using REALM) and their interpretation of hypothetical recurrence risk results from a genomic test, presented in several verbal and numerical formats. Analyses controlled for women's objective recurrence risk, age, income, and race. Results. Women with lower health literacy gave higher mean estimates of recurrence risk for a hypothetical group of women with early-stage breast cancer than did women with higher health literacy (52% v. 30%, P < 0:001). Women with lower health literacy also gave more variable estimates in this and several other tasks. When making chemotherapy decisions using risks presented in verbal formats, decisions by women with lower health literacy were less sensitive to the difference between low and high recurrence risk. Ease of understanding of risk formats differed by health literacy. Conclusions. Health literacy affected the meanings women assigned to recurrence risk when presented in certain formats. The greater variability in responding by women with lower health literacy supports the hypothesis that they have less precise mental representations of risk, but more research is needed to rule out other possible explanations.

Randomized Trial of Presenting Absolute v. Relative Risk Reduction in the Elicitation of Patient Values for Heart Disease Prevention With Conjoint Analysis

Griffith, J. M., Lewis, C. L., Hawley, S., Sheridan, S. L., Pignone, M. P. — Fri, 10 Apr 2009 11:12:28 PDT

Background . The authors performed a randomized controlled trial to test the effect of 2 different formats of risk reduction information when using conjoint analysis to elicit values about heart disease prevention. Methods . Participants ages 30 to 75 were enrolled and presented the same hypothetical scenario: a person with a 13% ten-year risk of heart disease. Participants then worked through a values elicitation exercise using conjoint analysis, making pairwise comparisons of hypothetical treatments that differed on 5 attributes. For the attribute ``ability to reduce heart attacks,'' participants were randomized to receive either absolute risk reduction (ARR) or relative risk reduction (RRR) information. Participants selected which attribute they felt was most important. Participants' responses to the pairwise comparisons were then used to generate their most important attribute using ordinary least squares regression. Outcomes included differences between groups in the proportion choosing and generating ability to reduce heart attacks as the most important attribute. Results. In total, 113 participants completed the study: mean age was 51, 29% were male, 52% were white, and 42% were African American. The proportion who selected the ability to reduce heart attacks as the most important treatment attribute did not differ significantly (64% RRR; 53% ARR, Fisher's P = 0.26). For the conjoint-generated most important attribute, those receiving the RRR version were significantly more likely to generate ability to reduce heart attacks as the most important attribute (59% RRR; 35% ARR, Fisher's P = 0.01). Discussion . Risk presentation format appears to affect the perceived value of different treatment attributes generated from conjoint analysis.

The Psychosocial Effect of Thoughts of Personal Mortality on Cardiac Risk Assessment

Arndt, J., Vess, M., Cox, C. R., Goldenberg, J. L., Lagle, S. — Fri, 10 Apr 2009 11:12:28 PDT

Background . Prejudice by medical providers has been found to contribute to differential cardiac risk estimates. As such, empirical examinations of psychological factors associated with such biases are warranted. Considerable psychological research implicates concerns with personal mortality in motivating prejudicial biases. The authors sought to examine whether provoking thoughts of mortality among medical students would engender more cautious cardiac risk assessments for a hypothetical Christian than for a Muslim patient. Methods . During the spring of 2007, university medical students (N = 47) were randomly assigned to conditions in a 2 (mortality salience) x 2 (patient religion) full factorial experimental design. In an online survey, participants answered questions about their mortality or about future uncertainty, inspected emergency room admittance forms for a Muslim or Christian patient complaining of chest pain, and subsequently estimated risk for coronary artery disease, myocardial infarction, and the combined risk of either of the two. A composite risk index was formed based on the responses (on a scale of 0— 100) to each of the 3 cardiac risk questions. Results . Reminders of mortality interacted with patient religion to influence risk assessments, F_1,41 = 11:57, P = 0:002, ² =:22. After being reminded of mortality, participants rendered more serious cardiac risk estimates for a Christian patient (F_1,41 = 8:66, P = 0:01) and less serious estimates for a Muslim patient (F_1,41 = 4:08, P=0:05). Conclusion . Reminders of personal mortality can lead to biased patient risk assessment as medical providers use their cultural identification to psychologically manage their awareness of death.

Intertemporal Tradeoffs: Perceiving the Risk in the Benefits of Marijuana in a Prospective Study of Adolescents and Young Adults

Goldberg, J. H., Millstein, S., Schwartz, A., Halpern-Felsher, B. — Fri, 10 Apr 2009 11:12:28 PDT

Purpose . Intertemporal tradeoffs characterize the decision to use drugs: pleasure now traded off against the possibility of pain later. Traditional approaches have examined whether individuals use drugs because they either seek immediate benefit or fail to appreciate long-term risk. We asked whether risk taking might also result from failing to appreciate benefits. We refer to this as risk in the benefits (RIBs), an understanding that one's first drug experience can be so good, that a person may not want (or be able) to stop, putting him/her on a path that leads directly to addiction. Methods . In total, 304 participants, 160 adolescents and 144 young adults, participated in a longitudinal study on marijuana use and other risky health behaviors. Results. The failure to perceive the RIBs of marijuana use led to increased risk taking 1 year later within 3 different health behaviors: alcohol, tobacco, and sexual risk-taking. Greater appreciation of RIBs predicted significantly less future risk taking over-and-above all the traditional cognitive and behavioral predictors, and RIBs were the only significant cognitive predictor when all were included in 1 model. RIBs also partially mediated the relationship between past and future risk taking, over and above the strongest predictors of risk taking. Conclusions. Failing to appreciate the impact of short-term benefits within the context of long-term risk increased future risk taking. Interventions that enhance the salience of RIBs may represent a new approach to reducing the likelihood that individuals will take risks with their health.

Anchoring-and-Adjustment Bias in Communication of Disease Risk

Senay, I., Kaphingst, K. A. — Fri, 10 Apr 2009 11:12:29 PDT

Over the next decade, advances in genomics will make it increasingly possible to provide patients with personalized, genetic-based risks of common diseases, allowing them the opportunity to take preventive steps through behavioral changes. However, previous research indicates that people may insufficiently adjust their subjective risk to the objective risk value communicated to them by a healthcare provider, a phenomenon called anchoring-and-adjustment bias. In this narrative review, we analyze existing research on how patients process disease-risk information, and the processing biases that may occur, to show that the bias observed in disease-risk communication is potentially malleable to change. We recommend that, to reduce this bias and change patients' misperceptions of disease risk in clinical settings, future studies investigate the effects of forewarning patients about the bias, tailoring risk information to their numeracy level, emphasizing social roles, increasing motivation to form accurate risk perception, and reducing social stigmatization, disease worry and information overload.

Computer and Internet Use in a Community Health Clinic Population

Peterson, N. B., Dwyer, K. A., Mulvaney, S. A. — Fri, 10 Apr 2009 11:12:29 PDT

Objective . To determine if patients from a community health clinic have access to computers and/or the Internet and if they believe a computer is useful in their medical care. Methods. A convenience sample of 100 subjects, aged 50 years and older, from a community health clinic in Nashville, Tennessee, completed a structured interview and a health literacy assessment. Results. Of the 100 participants, 40 did not have any computer access, 27 had computer but not Internet access, and 33 had Internet access. Participants with computer access (with or without Internet) had higher incomes, higher educational status, and higher literacy status than those without computer access. Of participants reporting current computer use (n = 54), 33% reported never using their computer to look up health and medical information. Of those who ``never'' used their computer for this activity, 54% reported they did not have Internet connectivity, whereas 31% reported they did not know how to use the Internet. Although this group of individuals reported that they were comfortable using a computer (77%), they reported being uncomfortable with accessing the Internet (53%). Conclusions. Not only does access to computers and the Internet need to be improved before widespread use by patients, but computer users will need to be instructed on how to navigate the Internet.

Value for Money in Changing Clinical Practice: Should Decisions about Guidelines and Implementation Strategies Be Made Sequentially or Simultaneously?

Hoomans, T., Severens, J. L., Evers, S. M. A. A., Ament, A. J. H. A. — Fri, 10 Apr 2009 11:12:29 PDT

Decisions about clinical practice change, that is, which guidelines to adopt and how to implement them, can be made sequentially or simultaneously. Decision makers adopting a sequential approach first compare the costs and effects of alternative guidelines to select the best set of guideline recommendations for patient management and subsequently examine the implementation costs and effects to choose the best strategy to implement the selected guideline. In an integral approach, decision makers simultaneously decide about the guideline and the implementation strategy on the basis of the overall value for money in changing clinical practice. This article demonstrates that the decision to use a sequential v. an integral approach affects the need for detailed information and the complexity of the decision analytic process. More importantly, it may lead to different choices of guidelines and implementation strategies for clinical practice change. The differences in decision making and decision analysis between the alternative approaches are comprehensively illustrated using 2 hypothetical examples. We argue that, in most cases, an integral approach to deciding about change in clinical practice is preferred, as this provides more efficient use of scarce health-care resources.

Competence of General Practitioners in Giving Advice about Changes in Lifestyle to Hypertensive Patients

Windak, A., Gryglewska, B., Tomasik, T., Narkiewicz, K., Grodzicki, T. — Fri, 10 Apr 2009 11:12:29 PDT

Objective . The aim of this study was to assess the advice about lifestyle changes that general practitioners (GPs) gave hypertensive patients with different levels of cardiovascular risk. Design and Methods. A stratified sample of primary health care physicians in Poland completed a questionnaire consisting of 8 case vignettes that differed with regard to 3 major variables: 1) the level of blood pressure (high-normal blood pressure or grade 2 hypertension), 2) the presence of selected risk factors such as smoking and obesity, and 3) diabetes mellitus. The case vignettes were followed by a series of open questions. Results. The response rate was 65% (125/192 selected physicians responded). The mean age was 45.2 ± 8.1 years, and the average length of professional experience in primary care was 14.7 ± 9.3 years. For 1000 potential clinical decisions considered, all expected pieces of advice were given in 18.3% of situations, whereas in 11.5%, no advice concerning nonpharmacological treatment was provided. In 70.2% of situations, Polish primary health physicians gave incomplete advice. The average percentage of expected advice in all cases was 57.2% ± 30.8%. The presence of hypertension along with other risk factors of cardiovascular disease was associated with better quality advice (P < 0.001), but the coexistence of diabetes mellitus had opposite consequences (P<0.001). Conclusions. Despite the existence of well-known guidelines for the treatment of hypertension in Poland, GPs rarely give complete lifestyle advice, particularly for patients with cardiovascular risk due to high-normal blood pressure and diabetes.

The Cost-Effectiveness of Screening for Hereditary Hemochromatosis in Germany: A Remodeling Study

Rogowski, W. H. — Fri, 10 Apr 2009 11:12:29 PDT

Objective . Genetic tests for hereditary hemochromatosis (HH) are currently included in the German ambulatory care reimbursement scheme but only for symptomatic individuals and the offspring of HH patients. This study synthesizes the most current evidence to examine whether screening in the broader population is cost-effective and to identify the best choice of initial and follow-up screening tests. Methods. A probabilistic decision-analytic model was constructed to calculate cost per life year gained (LYG) for HH screening among male Caucasians aged 30. Three strategies were considered in both the general population and male offspring of HH patients: phenotypic (transferrin saturation, TS), genotypic (C282Y mutation), and sequential (genotype if TS is elevated) screening. Results. The incremental cost-effectiveness of sequential screening among male offspring, sequential population-wide screening, and genotypic screening is 41 000, 124 000, and 161 000 /LYG, respectively. All other strategies were subject to simple or extended dominance. The results are subject to high uncertainty. The most influential parameters in the deterministic one-way sensitivity analysis are discounting of life years gained and the adherence of patients to preventive phlebotomy. Discussion . The current German policy of only screening at-risk individuals is consistent with health economic decision making based on typically accepted thresholds. However, conducting the DNA test after the first elevated TS result is more cost-effective than waiting for a second TS result as recommended by the German guidelines. Further empirical work regarding adherence to long-term prevention recommendations and explicit and well-justified guidance for the choice of discount rates in German economic evaluation are needed.

Development of a Clinical Prediction Model to Calculate Patient Life Expectancy: The Measure of Actuarial Life Expectancy (MALE)

Clarke, M.G., Kennedy, K.P., MacDonagh, R.P. — Fri, 10 Apr 2009 11:12:29 PDT

Objectives. To develop a clinical prediction model enabling the calculation of an individual patient's life expectancy (LE) and survival probability based on age, sex, and comorbidity for use in the joint decision-making process regarding medical treatment. Methods. A computer software program was developed with a team of 3 clinicians, 2 professional actuaries, and 2 professional computer programmers. This incorporated statistical spreadsheet and database access design methods. Data sources included life insurance industry actuarial rating factor tables (public and private domain), Government Actuary Department UK life tables, professional actuarial sources, and evidence-based medical literature. The main outcome measures were numerical and graphical display of comorbidity-adjusted LE; 5-, 10-, and 15-year survival probability; in addition to generic UK population LE. Results. Nineteen medical conditions, which impacted significantly on LE in actuarial terms and were commonly encountered in clinical practice, were incorporated in the final model. Numerical and graphical representations of statistical predictions of LE and survival probability were successfully generated for patients with either no comorbidity or a combination of the 19 medical conditions included. Validation and testing, including actuarial peer review, confirmed consistency with the data sources utilized. Conclusions. The evidence-based actuarial data utilized in this computer program design represent a valuable resource for use in the clinical decision-making process, where an accurate objective assessment of patient LE can so often make the difference between patients being offered or denied medical and surgical treatment. Ongoing development to incorporate additional comorbidities and enable Web-based access will enhance its use further.

Validation of an Automated Safety Surveillance System with Prospective, Randomized Trial Data

Fri, 10 Apr 2009 11:12:29 PDT

Objective. We sought to validate 3 methods for automated safety monitoring by evaluating clinical trials with elevated adverse events. Methods. An automated outcomes surveillance system was used to retrospectively analyze data from 2 randomized, TIMI multicenter trials. Trial A was stopped early due to elevated 30-day mortality rates in the intervention arm. Trial B was not stopped early, but there was transient concern regarding 30-day intracranial hemorrhage rates. We compared statistical process control (SPC), logistic regression risk adjusted SPC (LR-SPC), and Bayesian updating statistic (BUS) methods with a standard prospective 2-arm event rate analysis. Each method compares observed event rates to alerting boundaries established with previously collected data. In this evaluation, the control arms approximated prior data, and the intervention arms approximated the observed data. Results. Trial A experienced elevated 30-day mortality rates beginning 7 months after the start of the trial and continuing until termination at month 14. Trial B did not experience elevated major bleeding rates. Combining the alerting performance of each method across both trials resulted in sensitivities and specificities of 100% and 85% for SPC, 0% and 100% for BUS, and 100% and 93% for both LR-SPC models, respectively. Conclusion. Both SPC and LR-SPC methods correctly identified the majority of months during which the cumulative event rates were elevated in trial A but were susceptible to false positive alerts in trial B. The BUS method did not result in any alerts in either trial and requires revision.

Impact of the Scale Upper Anchor on Health State Preferences

King, J. T., Tsevat, J., Roberts, M. S. — Fri, 10 Apr 2009 11:12:29 PDT

Background . Some studies of patient preferences use a measurement scale with an upper anchor point of ``perfect health'' (``Q scale''), whereas others use ``disease free'' (``q scale''). Different measurement scales can lead to problems with interpreting and comparing study results. In an earlier study of patients with degenerative spine disease, the authors showed systematic differences between preferences measured on the Q v. q scales. They sought to validate the differences in Q and q scale measurements in a separate patient population. Methods. The authors measured preferences for current health in a population of 186 patients with cerebral aneurysms using the standard gamble (SG), time tradeoff (TTO), and willingness to pay (WTP) methods. Values were measured on both the Q and q scales and compared with the Wilcoxon signed-rank test. The authors used an additive utility model to calculate aneurysm-specific disutility. Results. Q and q scale values were different for the SG (mean values Q: 0.77, q: 0.80, P = 0.034), TTO (Q: 0.79, q: 0.81, P = 0.065), and WTP (Q : $117,600, q: $94,500, P < 0.001). Preference values were consistent with patients valuing perfect health more than aneurysm-free health. Cerebral aneurysms accounted for 43% to 86% of total disutility. Conclusions. Similar to earlier findings in patients with a degenerative spine condition, this validation study showed that preferences for current health in patients with cerebral aneurysms are different when measured on the Q and q scales. Investigators should be mindful of the impact of the scale's upper anchor point on preference values when conducting and interpreting preference studies.