1. Little cost difference between CT angiography and stress test for diagnosing heart disease
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For patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) and functional diagnostic testing strategies have similar costs through 3 years of follow up. Results of this prospective economic study are published in Annals of Internal Medicine.
Chest pain is a common reason for patients to seek medical care and a challenge for doctors who must diagnose the cause. Typically, clinicians rely on health history and noninvasive tests to assess for CAD, such as CTA and functional stress tests. The recent PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) trial examined the effect of these different diagnostic testing strategies for CAD on patient outcomes and found little difference between them. A planned secondary aim of PROMISE was to conduct an economic analysis to assess cost differences between the approaches.
Researchers analyzed economic data for 9,649 patients enrolled in PROMISE between July 2010 and September 2013. They looked at cost of the initial outpatient testing strategy, hospital-based costs, and physician fees for the first 90 days and then estimated out to 3 years. The data showed that an initial CTA strategy had costs similar to those of a functional stress testing strategy, but patterns of care differed. Patients in the CTA group had less follow-up noninvasive testing and more invasive catheterization and revascularization. After 90 days, the choice of test had little effect on differential costs.
According to the author of an accompanying editorial, the PROMISE economic analysis is disappointing because it lacks data on treatment costs associated with heart disease. Stable ischemic heart disease therapeutic management includes a focus on symptom control, lifestyle modification, and targeted risk factor modifying treatments, which may impart a heavy economic burden on many patients. The author suggests further research to determine the value of symptom-guided treatment without diagnostic testing as a way to eliminate the commonplace finding of "testing begetting more testing."
Note: For an embargoed PDF, please contact Cara Graeff. For an interview with the lead author, Dr. Daniel Mark, please contact Sarah Avery at firstname.lastname@example.org or 919-660-1306.
2. Novel trial approaches may help to make cancer treatments more precise
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Newer trial designs may help to personalize cancer treatments based on DNA alterations in tumors, rather than on primary tumor site or stage of disease. The result could be more effective treatments. A summary of three of these novel trial designs is published in Annals of Internal Medicine.
Traditional trial designs in oncology have proceeded along three phases of research. Phase 1 oncology trials seek to find the maximum dose tolerated by the patient's normal tissues among patients with metastatic disease of various primary tumor sites that were resistant to known treatments; phase 2 trials are used to evaluate antitumor drug activity in patients with advanced disease of a given primary tumor site in which other treatments have failed; and phase 3 trials are randomized controlled trials (RCTs) comparing a new treatment to a standard-of-care control in patients who are representative of the general population of patients with a specified primary site and stage of cancer. However, developments in tumor biology and genomics have indicated that tumors of a primary site represent a heterogeneous collection of diseases that differ with regard to DNA drivers. This means that conventional approaches to clinical trial design and analysis may no longer be appropriate as clinicians look to base treatments on molecular phenotypes. This movement is known as precision medicine.
The author describes new clinical trial designs in oncology that may help to advance precision medicine. In phase 2 basket trials, which can be randomized or nonrandomized and include a single drug or multiple individual drugs, patient eligibility is based on a defined genomic alteration rather than on primary tumor site. For example, eligibility may require that the tumor contains a V600E mutation in the BRAF gene in a patient with any type of solid tumor. Phase 3 enrichment designs conducted for regulatory approval have eligibility limited to patients with a single primary site of disease and genomic alteration. Approval of a drug is accompanied by an approval of a companion diagnostic for identifying the patients who have tumors for which the drug is effective. For example, trastuzumab was approved for breast cancer with an assay for amplification of the HER2 gene overexpression of the HER2 protein as the companion diagnostic test. And finally, phase 3 umbrella designs involve several molecularly targeted test drugs and a population of patients with a single primary site of disease. Phase 3 umbrella trials consist of a combination of several enrichment designs conducted with a common genomic alteration testing infrastructure. For example, in the Lung-MAP (Lung Master Protocol-phase II/III Biomarker Driven Master Protocol for Second Line Therapy of Squamous Cell Lung Cancer) study, patients with advanced squamous cell lung cancer who have undergone one previous treatment are screened for genomic alterations in more than 200 genes using a sequencing platform that has been analytically validated for accuracy. As a result of this tumor characterization, patients are recommended for 1 of 5 subtrials with the umbrella framework.
These new trial designs are promising in oncology precision medicine and have may indications in other disease areas, as well, according to the author.
Note: For an embargoed PDF, please contact Cara Graeff. For an interview with the lead author, Dr. Richard Simon, please contact the National Cancer Institute Press Officers at email@example.com or 301-496-6641.
Also new in this issue:
Transparent Electronic Health Records and Lagging Laws
Bryan S. Lee, MD, JD; Jan Walker, RN, MBA; Tom Delbanco, MD, and Joann G. Elmore, MD, MPG
Ideas and Opinions