The CREATE Method for Expressing Continuous Outcome Data in Absolute Terms for Use in Patient Treatment Decision Aids: A Validation Study.

BACKGROUND: Patient decision aids (PtDAs) supplement advice from health care professionals by communicating the absolute risk or benefit of treatment options (i.e., X/100). As such, PtDAs have been amenable to binary outcomes only. We aimed to develop and test the validity of the Conversion to Risk Estimates through Application of Normal Theory (CREATE) method for estimating absolute risk based on continuous outcome data. METHODS: CREATE is designed to derive an estimate of the proportion of those who experience a clinically relevant degree of change (CRDoC). We used a 2-stage validation process using real and simulated change score data, respectively. First, using raw data from published intervention trials, we calculated the proportion of patients with a CRDoC and compared that with our CREATE-derived estimate using chi-square tests of association. Second, 200,000 simulated distributions of change scores were generated with widely varying distribution characteristics. Actual and CREATE-derived estimates were compared for each simulated distribution, and relative differences were summarized graphically. RESULTS: The absolute difference between the estimated and actual CRDoC did not exceed 5% for any of the samples based on real data. Applying the CREATE method to 200,000 simulated scenarios demonstrated that the CREATE method should be avoided for outcomes where the underlying distribution can be reasonably assumed to have high levels of skew or kurtosis. CONCLUSION: Our results suggest that standard statistical theory can be used to estimate continuous outcomes in absolute terms with reasonable accuracy for use in PtDAs; caution is advised if outcome summary statistics are assumed to have been derived from highly skewed distributions.

Development of a patient decision aid for people with refractory angina: protocol for a three-phase pilot study.

BACKGROUND: Refractory angina is a severe chronic disease, defined as angina which cannot be controlled by usual treatments for heart disease. This disease is frightening, debilitating, and difficult to manage. Many people suffering refractory have inadequate pain relief, continually revisit emergency departments for help, undergo repeated cardiac investigations, and struggle with obtaining appropriate care. There is no clear framework to help people understand the risks and benefits of available treatment options in Canada. Some treatments for refractory angina are invasive, while others are not covered by provincial health insurance plans. Effective care for refractory angina sufferers in Canada is critically underdeveloped; it is important that healthcare professionals and refractory angina sufferers alike understand the treatment options and their implications. This proposal builds on the recent Canadian practice guidelines for the management of refractory angina. We propose to develop a decision support tool in order to help people suffering from refractory angina make well-informed decisions about their healthcare and reduce their uncertainty about treatment options. METHODS: This project will be conducted in three phases: a) development of the support tool with input from clinical experts, the Canadian refractory angina guidelines, and people living with refractory angina, b) pilot testing of the usability of the tool, and c) formal preliminary evaluation of the effectiveness of the support tool to help people make informed decisions about treatment options. DISCUSSION: A decision support tool for refractory angina is needed and the available data suggest that by developing such a tool, we may be able to help refractory angina sufferers better understand their condition and the effectiveness of available treatment options (in their respective clinical settings) as well as their implications (e.g. risks vs. benefits). By virtue of this tool, we may also be able to facilitate identification and inclusion of patients' values and preferences in the decision making process. This is particularly important as refractory angina is an intractable condition, necessitating that the selected course of treatment be lifelong. This study will yield a much needed patient decision aid for people living with refractory angina and pilot data to support a subsequent effectiveness study.

Spinal cord stimulation therapy for patients with refractory angina who are not candidates for revascularization.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of spinal cord stimulation (SCS) for refractory angina. MATERIALS AND METHODS: This multicenter, randomized, single-blind, controlled trial evaluated SCS in two patient groups: high stimulation (HS) (treatment) and low stimulation (LS) (control). The HS group controlled SCS with a programmer for a minimum of two hours four times daily. The LS group received SCS therapy above the paresthesia threshold for one min once daily. The primary efficacy endpoint was number of angina attacks recorded by patients at six months. The primary safety endpoint was the major adverse cardiac event (MACE) rate at six months. RESULTS: Due to slow enrollment, a futility analysis was performed, resulting in early termination of the study. Sixty-eight patients were randomized after implantation. Mean change in angina attacks per day from baseline to six months was -1.19 ± 2.13 (HS) and -1.29 ± 1.66 (LS). The difference from baseline was significant within each group (both p < 0.001) but not between groups (p = 0.45). Total exercise time and time to angina onset increased significantly from baseline to six months within each group (both p = 0.02 and 0.002) but not between groups (p = 0.52 and 0.51). MACE was similar between groups. CONCLUSION: Although this study was terminated early, the results obtained at six months suggest that SCS (HS) is not more effective than the control (LS) in patients with refractory angina.

Management of patients with refractory angina: Canadian Cardiovascular Society/Canadian Pain Society joint guidelines.

Refractory angina (RFA) is a debilitating disease characterized by cardiac pain resistant to conventional treatments for coronary artery disease including nitrates, calcium-channel and ß-adrenoceptor blockade, vasculoprotective agents, percutaneous coronary interventions, and coronary artery bypass grafting. The mortality rate of patients living with RFA is not known but is thought to be in the range of approximately 3%. These individuals suffer severely impaired health-related quality of life with recurrent and sustained pain, poor general health status, psychological distress, impaired role functioning, and activity restriction. Effective care for RFA sufferers in Canada is critically underdeveloped. These guidelines are predicated upon a 2009 Canadian Cardiovascular Society (CCS) Position Statement which identified that underlying the problem of RFA management is the lack of a formalized, coordinated, interprofessional strategy between the cardiovascular and pain science/clinical communities. The guidelines are therefore a joint initiative of the CCS and the Canadian Pain Society (CPS) and make practice recommendations about treatment options for RFA that are based on the best available evidence. Concluding summary recommendations are also made, giving direction to future clinical practice and research on RFA management in Canada.

Treatment of inoperable coronary disease and refractory angina: spinal stimulators, epidurals, gene therapy, transmyocardial laser, and counterpulsation.

Intractable angina from refractory coronary disease is a severe form of myocardial ischemia for which revascularization provides no prognostic benefit. Inoperable coronary disease is also accompanied by a "vicious cycle" of myocardial dystrophy from a chronic alteration of the cardiac sympathetic tone and sensitization of damaged cardiac tissues. Several adjunctive treatments have demonstrated efficacy when revascularization is either unsuccessful or contraindicated. Spinal cord stimulation modifies the neurologic input and output of the heart by delivering a very low dose of electrical current to the dorsal columns of the high thoracic spinal cord. Neural fibers then release CGRP and other endogenous peptides to the coronary circulation reducing myocardial oxygen demand and enhancing vasodilation of collaterals to improve the myocardial blood flow of the most diseased regions of the heart. Randomized study has shown the survival data at five years is comparable to bypass for high-risk patients. Transmyocardial laser revascularization creates small channels into ischemic myocardium in an effort to enhance flow though studies have shown no improvement in prognosis over medical therapy alone. Enhanced external counterpulsation uses noninvasive pneumatic compression of the legs to improve diastolic filling of the coronary vessels and promote development of collateral flow. The compressor regimen requires thirty-five hours of therapy over a seven-week treatment period. Therapeutic angiogenesis requires injection of cytokines to promote neovascularization and improve myocardial perfusion into the regions affected by chronic ischemia. Phase 3 trials are pending. High thoracic epidural blockade produces a rapid and potent sympatholysis, coronary vasodilation and reduced myocardial oxygen demand in refractory coronary disease. This technique can be used as an adjunct to bypass surgery or medical therapy in chronic or acute unstable angina. Epidurals are easy to perform and often available for outpatient or inpatient use. The rapid anti-ischemic effect may complement therapeutic angiogenesis or other interventions with delayed onset to clinical benefit. A new era for interventional and implant cardiology is beginning to emerge as more clinicians, including cardiologists, gradually learn new procedures to safely provide more therapeutic options for patients suffering refractory angina.