Decision Analysis in SHared decision making for Thromboprophylaxis during Pregnancy (DASH-TOP): a sequential explanatory mixed-methods pilot study.

OBJECTIVES: To gain insight into formal methods of integrating patient preferences and clinical evidence to inform treatment decisions, we explored patients' experience with a personalised decision analysis intervention, for prophylactic low-molecular-weight heparin (LMWH) in the antenatal period. DESIGN: Mixed-methods explanatory sequential pilot study. SETTING: Hospitals in Canada (n=1) and Spain (n=4 sites). Due to the COVID-19 pandemic, we conducted part of the study virtually. PARTICIPANTS: 15 individuals with a prior venous thromboembolism who were pregnant or planning pregnancy and had been referred for counselling regarding LMWH. INTERVENTION: A shared decision-making intervention that included three components: (1) direct choice exercise; (2) preference elicitation exercises and (3) personalised decision analysis. MAIN OUTCOME MEASURES: Participants completed a self-administered questionnaire to evaluate decision quality (decisional conflict, self-efficacy and satisfaction). Semistructured interviews were then conducted to explore their experience and perceptions of the decision-making process. RESULTS: Participants in the study appreciated the opportunity to use an evidence-based decision support tool that considered their personal values and preferences and reported feeling more prepared for their consultation. However, there were mixed reactions to the standard gamble and personalised treatment recommendation. Some participants could not understand how to complete the standard gamble exercises, and others highlighted the need for more informative ways of presenting results of the decision analysis. CONCLUSION: Our results highlight the challenges and opportunities for those who wish to incorporate decision analysis to support shared decision-making for clinical decisions.

Individualizing therapy to prevent long-term consequences of estrogen deficiency in postmenopausal women.

BACKGROUND: Alendronate sodium and raloxifene hydrochloride were recently approved for the prevention of postmenopausal osteoporosis, but data on their clinical efficacy are limited. We compared these drugs with hormone replacement therapy (HRT) to help women and physicians guide postmenopausal treatment decisions. OBJECTIVE: To help physicians understand how they can best help women choose the most beneficial therapy after menopause based on their individual risk profile. METHODS: We developed a decision analytic Markov model to compare the effects of alendronate therapy, raloxifene therapy, and HRT on risks of hip fracture, coronary heart disease (CHD), breast cancer, and life expectancy. Regression models linked individual risk factors to future disease risks and were modified by drug effects on bone density, lipid levels, and associated breast cancer effects. RESULTS: Hormone replacement therapy, alendronate therapy, and raloxifene therapy have similar predicted efficacies in preventing hip fractures (estimated relative risk, 0.57, 0.54, and 0.58, respectively). Hormone replacement therapy should be more than 10 times more effective than raloxifene therapy in preventing CHD, but raloxifene therapy may not induce breast cancer. Women at low risk for hip fracture, CHD, and breast cancer do not benefit significantly from any treatment. Among women at average risk, HRT was preferred unless raloxifene therapy could reduce the risk of breast cancer by at least 66%, compared with a 47% increase for HRT. Women at high risk for CHD benefit most from HRT; women at high risk for breast cancer but low risk for CHD benefit most from raloxifene therapy, but only if it lowers the risk of breast cancer. CONCLUSION: Because of significant differences in the impact of these drugs, treatment choice depends on an individual woman's risk for hip fracture, CHD, and breast cancer.

Cost-effectiveness of therapies for patients with nonvalvular atrial fibrillation.

BACKGROUND: The most appropriate treatment(s) for patients with atrial fibrillation remains uncertain. OBJECTIVE: To examine the cost-effectiveness of anti-thrombotic and antiarrhythmic treatment strategies for atrial fibrillation. METHODS: We performed decision and cost-effectiveness analyses using a Markov state transition model. We gathered data from the English-language literature using MEDLINE searches and bibliographies from selected articles. We obtained financial data from nationwide physician-fee references, a medical center's cost accounting system, and one of New England's larger managed care organizations. We examined strategies that included combinations of cardioversion, antiarrhythmic therapy with quinidine, sotalol hydrochloride, or amiodarone, and anticoagulant or antiplatelet therapy. RESULTS: For a 65-year-old man with nonvalvular atrial fibrillation, any intervention results in a significant gain in quality-adjusted life years (QALYs) compared with no specific therapy. Use of aspirin results in the largest incremental gain (1.2 QALYs). Cardioversion followed by the use of amiodarone and warfarin together is the most effective strategy, yielding a gain of 2.3 QALYs compared with no specific therapy. The marginal cost-effectiveness ratios of cardioversion followed by aspirin, with or without amiodarone, are $33800 per QALY and $10800 per QALY, respectively. Cardioversion followed by amiodarone and warfarin has a marginal cost-effectiveness ratio of $92400 per QALY compared with amiodarone and aspirin. Strategies that include cardioversion followed by either quinidine or sotalol are both more expensive and less effective than competing strategies. CONCLUSIONS: Cardioversion of patients with nonvalvular atrial fibrillation followed by the use of aspirin alone or with amiodarone has a reasonable marginal cost-effectiveness ratio. While cardioversion followed by the use of amiodarone and warfarin results in the greatest gain in quality-adjusted life expectancy, it is expensive (ie, has a high marginal cost-effectiveness ratio) compared with aspirin and amiodarone. Finally, for patients who are bothered little by symptoms of atrial fibrillation, cardioversion followed by either aspirin or warfarin without subsequent antiarrhythmic therapy is the treatment of choice.

Foot infections in diabetic patients. Decision and cost-effectiveness analyses.

OBJECTIVE: To examine the cost-effectiveness of approaches to the diagnosis and treatment of patients with type II (non-insulin-dependent) diabetes mellitus (NIDDM) who have foot infections and suspected osteomyelitis. DESIGN: Decision and cost-effectiveness analyses were performed using a Markov model. We examined the prevalence of osteomyelitis, the major complications and efficacies of long-term antibiotic therapy and surgery, and the performance characteristics of four diagnostic tests (roentgenography, technetium Tc 99m bone scanning, indium in 111-labeled white blood cell scanning, and magnetic resonance imaging). Data were drawn from the English-language literature using MEDLINE searches and bibliographies from selected articles. SETTING: Primary care. PATIENTS: Patients with NIDDM who had foot infections and suspected osteomyelitis but no signs of systemic toxicity. INTERVENTIONS: Following hospitalization for surgical débridement and intravenous antibiotic therapy: (1) treatment for presumed soft-tissue infection, (2) culture-guided empiric treatment for presumed osteomyelitis, (3) 71 combinations of diagnostic tests preceding antibiotic therapy for osteomyelitis, (4) 71 combinations of tests preceding amputation, and (5) immediate amputation. MAIN OUTCOME MEASURES: Quality-adjusted life expectancy, average costs. RESULTS: Culture-guided empiric treatment for osteomyelitis with 10 weeks of oral antibiotic therapy has similar effectiveness to testing followed by a long course of antibiotic therapy if any test result is positive. However, empiric treatment is the least expensive strategy. CONCLUSIONS: Noninvasive testing adds significant expense to the treatment of patients with NIDDM in whom pedal osteomyelitis is suspected, and such testing may result in little improvement in health outcomes. In patients without systemic toxicity, a 10-week course of culture-guided oral antibiotic therapy following surgical débridement may be as effective as and less costly than other approaches.

Screening for prostate cancer. A decision analytic view.

OBJECTIVE: To determine the clinical and economic effects of screening for prostate cancer with prostate-specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). DESIGN: Decision analytic cost-utility analysis comparing four screening strategies with a strategy of not screening. We assumed that the cancer detection rate and stage distribution were predicted by each combination of tests and that localized cancer was treated with radical prostatectomy. For each strategy, we calculated life expectancy, quality-adjusted life expectancy (QALE), and cost-utility ratios for unselected and high-prevalence populations. DATA: Probabilities and rates for clinical events were gathered from published data. We assessed utilities by the time-trade-off method using urologists, radiation oncologists, and internists as subjects. The Clinical Cost Manager at the New England Medical Center provided cost data. RESULTS: In unselected men between the ages of 50 and 70 years, screening with PSA or TRUS prolonged unadjusted life expectancy but diminished QALE. Screening with DRE alone yielded no reduction in mortality at any age. All programs increased costs. Results were sensitive only to assumptions about the efficacy of treatment. In high-prevalence populations, screening produced a similar pattern: gains in unadjusted life expectancy, losses in QALE, and increased costs. CONCLUSIONS: Our analysis does not support using PSA, TRUS, or DRE to screen asymptomatic men for prostatic cancer. Screening may result in poorer health outcomes and will increase costs dramatically. Assessment of comorbidity, risk attitude, and valuation of sexual function may identify individuals who will benefit from screening, but selecting high-prevalence populations will not improve the benefit of screening.

Effect of laboratory variation in the prothrombin-time ratio on the results of oral anticoagulant therapy.

BACKGROUND: Patients receiving long-term anticoagulant therapy may be subject to unnecessary risks of bleeding or thromboembolism because of variability in the commercial thromboplastins used to determine prothrombin time and consequent uncertainty about the actual intensity of anticoagulation. METHODS: We explored the effect of this uncertainty on the benefits and risks of anticoagulation in patients with prosthetic heart valves, using models of thromboembolic and hemorrhagic complications as a function of the intensity of anticoagulation, with quality-adjusted life expectancy and average variable costs used to describe outcomes. RESULTS: Anticoagulation provides a striking benefit for patients whose treatment is conducted within the recommended range of the international normalized ratio (INR)--i.e., 2.5 to 3.5--but if uncertainty about the laboratory results causes the intensity of anticoagulation to fall outside this range, the gain becomes smaller. Uncertainty about the true intensity of anticoagulation may reduce the potential gain in life expectancy, adjusted for quality of life, by more than half and may increase the ratio of costs to effectiveness to almost five times the optimal value. Variability in the intensity of anticoagulation is even greater if older recommendations advocating a higher level of anticoagulation are followed. CONCLUSIONS: Uncertainty about the sensitivities of the commercially available thromboplastins used in the United States can have important clinical and economic effects. This problem could be eliminated if clinical laboratories uniformly reported the intensity of anticoagulation as the INR, by adjusting prothrombin-time ratios for variability in thromboplastins.

Management and prevention of thromboembolic events in patients with cancer-related hypercoagulable states: a risky business.

OBJECTIVE: To determine the optimal strategy for managing and preventing thromboembolic events in malignancy-associated hypercoagulable states. DESIGN: A Markov-based decision and cost-effectiveness analysis was performed. The authors explicitly considered consequences of embolic and bleeding events, filter complications, and cancer-related excess mortality. Data were drawn from the current literature. The main outcome measure for each strategy was the quality-adjusted life expectancy and the total average variable costs. SUBJECTS: Patients with advanced malignancies prone to develop thromboembolic events, patients with acute proximal deep venous thrombosis (DVT), and patients who have survived a first episode of pulmonary embolism (PE). INTERVENTIONS: The authors considered three different interventions: 1) OBSERVATION, in which neither anticoagulant therapy nor filter placement is pursued, 2) ANTICOAGULATION, in which long-term anticoagulant therapy is started immediately, and 3) VENA CAVAL FILTER. MAIN RESULTS: Vena caval filter was the preferred strategy for every malignancy studied, yielding an 11% gain in quality-adjusted life expectancy, compared with observation, for patients with acute DVT, and an 18% gain for patients having survived a PE. Anticoagulant therapy yielded gains of 9% and 16%, respectively. Compared with anticoagulant therapy, filter was less costly due to the avoidance of additional expenses incurred by bleeding events. Prophylactic therapy was the least effective of the three strategies examined. CONCLUSIONS: Vena caval filter placement and long-term anticoagulation therapy yield similar outcomes in the setting of cancer-related hypercoagulable states. However, filter insertion is less expensive than anticoagulation. Given the short life expectancy and morbidity of patients with end-stage malignancy, patient preferences for health states must be considered in the decision-making process. If active treatment is pursued, vena caval filter should be used as a primary therapy. Prophylactic therapy is not warranted in any circumstance.

Prophylactic use of the intra-aortic balloon pump in high-risk cardiac patients undergoing noncardiac surgery: a decision analytic view.

OBJECTIVE: As the indications for the intra-aortic balloon pump (IABP) continue to evolve, a potential new use may be the prophylactic preoperative insertion of the IABP in the high-risk cardiac patient undergoing noncardiac surgery. Our objective is to present a general approach to the high-risk cardiac patient who may benefit from the prophylactic insertion of the IABP. DESIGN: Case reports and a decision analysis. METHODS: A decision model was constructed that weighs the risk of life-threatening postoperative complications against the risk of vascular complications, including surgery and possible amputation, from IABP insertion. RESULTS AND CONCLUSIONS: A review of the literature identified 10 patients who underwent IABP placement prior to noncardiac surgery. These patients, along with our three cases, define a population of patients for whom the prophylactic IABP may be useful. This population includes patients with coronary artery disease (CAD) for whom bypass grafting is not an option due to: (1) inoperable CAD; (2) a severe coexisting disease process (such as a malignancy); or (3) the emergent nature of the noncardiac procedure. The decision analysis suggests that patients whose preoperative assessment places them at very high risk for postoperative complications (Goldman class IV or Detsky class III undergoing major surgery) may benefit the most from prophylactic placement of an IABP prior to noncardiac surgery.

Anticoagulation for noncardiac procedures in patients with prosthetic heart valves. Does low risk mean high cost?

Hospitalizations for patients with prosthetic heart valves undergoing noncardiac surgery are frequently prolonged for intravenous heparin therapy to decrease the incidence of thromboembolism while patients are not taking oral anticoagulant agents. Because the rate of thromboembolic events is quite low and the period of increased risk is very short, the cost of preventing these rare events can be great. We performed cost-effectiveness analyses addressing these issues. We calculated the marginal cost per additional quality-adjusted year of life gained per thromboembolic event averted and per death averted. We conclude that the marginal cost of prolonging hospitalization to administer heparin is prohibitively high compared with most contemporary therapies, except when the patient has the most thrombogenic of valves. We also discuss the ethical and legal ramifications of integrating the results of cost-effectiveness analyses into clinical practice.

Automated critiquing of medical decision trees.

The authors developed a decision tree-critiquing program (called BUNYAN) that identifies potential modeling errors in medical decision trees. The program's critiques are based on the structure of a decision problem, obtained from an abstract description specifying only the basic semantic categories of the model's components. A taxonomy of node and branch types supplies the primitive building blocks for representing decision trees. Bunyan detects potential problems in a model by matching general pattern expressions that refer to these primitives. A small set of general principles justifies critiquing rules that detect four categories of potential structural problems: impossible strategies, dominated strategies, unaccountable violations of symmetry, and omission of apparently reasonable strategies. Although critiquing based on structure alone has clear limitations, principled structural analysis constitutes the core of a methodology for reasoning about decision models.

Aortic aneurysm in a 74-year-old man with coronary disease and obstructive lung disease: is double jeopardy enough?

A previous decision analysis examined a patient with severe CAD, diminished ventricular function, and an abdominal aortic aneurysm and also concluded that CABG followed by aneurysm repair was optimal. This patient, who had well-preserved cardiac function but severely compromised pulmonary status, stood to gain less from CABG than would a patient with more severe coronary disease, thus accounting for the "close-call" between the CABG-AAA and AAA only strategies. Nevertheless, the analysis did emphasize the benefit of aneurysm repair, whether done alone or after CABG. The analysis also highlighted the significant risk of aneurysm rupture the patient is exposed to while recovering from CABG surgery. The operative mortality risks of the two procedures are similar; thus, the patient's total operative risk is approximately doubled if he undergoes both procedures rather than aneurysm repair alone. The key question raised by the analysis is whether this double jeopardy is more than compensated by the degree to which prior CABG reduces both short-term cardiac risk at subsequent aneurysm repair and long-term cardiac mortality. For this patient, who had good cardiac function, the gains appeared sufficient to offset the interval risk of aneurysm rupture and the additional risk associated with a surgical procedures. THE REAL WORLD The patient indeed underwent and tolerated CABG, although he had a stormy prolonged postoperative course due to pulmonary failure. After discharge from the hospital, he declined readmission for repair of the aneurysm. We did not model that possibility, clearly an inadequacy in our tree. Some six months later, the patient was still alive and was, reluctantly, readmitted for aneurysmorrhaphy. At that time, however, his pulmonary function had deteriorated and both the anesthesiologist and the pulmonary consultant stated unequivocally that further surgery was now impossible. In retrospect, the expected utility of CABG without aneurysm repair (thus providing only a decrease in the long-term mortality risk from his CAD) would have been 1.95 (DEALE) or 2.06 (Markov) years. Sensitivity analysis revealed that, even if long-term cardiac risk were completely eliminated by CABG, immediate aneurysm repair would have been a better approach had the patient's physicians known he would be likely to refuse or not be a candidate for the second operation. In summary, although the patient's comorbidities did indeed place him at significant operative risk for either aneurysmorrhaphy alone or two sequential procedures, the benefits to be gained were shown to far outweigh the risks when compared with expectant observation.(ABSTRACT TRUNCATED AT 400 WORDS)

Warfarin for dilated cardiomyopathy: a bloody tough pill to swallow?

Although current recommendations for the treatment of dilated cardiomyopathy include long-term anticoagulation to diminish the likelihood of systemic embolization, there have been no clinical trials examining the effectiveness of anticoagulation in preventing systemic embolization in these patients. Furthermore, those recommendations do not address the issue of the quality of life associated with long-term warfarin therapy. Using decision analysis, the authors examined the benefits and risks of long-term anticoagulation for patients 35 to 75 years of age who have dilated cardiomyopathy. The results show that anticoagulant therapy increases quality-adjusted life expectancy by 76 to 128 days, depending on the patient's age. Sensitivity analysis, however, demonstrates that the outcome is dependent on the disutility associated with long-term warfarin therapy. Interestingly, anticoagulation exerts most of its benefit by preventing pulmonary embolization, not systemic embolization. The authors conclude that the current recommendation to anticoagulate these patients, although probably correct for many patients, should take into consideration the change in lifestyle imposed by long-term anticoagulant therapy. For some patients, the benefit may not outweigh the sacrifice.