A Path to Better-Quality mHealth Apps (Preprint)

UNSTRUCTURED The rapid growth of mobile health (mHealth) apps has resulted in confusion among health care providers and the public about which products rely on evidence-based medicine. Only a small subset of mHealth apps are regulated by the US Food and Drug Administration. The system similar to that used to accredit and certify laboratory testing under the Clinical Laboratory Improvement Amendment offers a potential model for ensuring basic standards of quality and safety for mHealth apps. With these products expanding into the realm of diagnosis and treatment, physicians and consumers are in a strong position to demand oversight that delivers safe and high-quality mHealth apps.

Genomic alterations in 670 patients with diverse cancers analyzed by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA).

11593 Background: NGS of blood-derived ctDNA allows non-invasive tumor profiling. Liquid biopsy studies with clinical correlation have so far been mainly limited to small size cohorts. Methods: We performed comprehensive plasma genomic testing of ctDNA (NGS) in 670 patients (pts) (54-70 genes); Guardant Health, Inc.; (Clinical Laboratory Improvement Amendment certified and College of American Pathologists accredited). Results: The most represented cancers were gastrointestinal (31.8%), brain (22.7%), and lung (20.7%) (Table). Sixty-three percent of pts (N = 423) had ≥1 alteration. The most frequent alterations (characterized and variants of unknown significance (VUSs)) were in TP53 (32.5% of pts), followed by EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, the breakdown was 30.7% ( TP53), 7.6% ( EGFR), 12.2% ( KRAS), and 7.7% ( PIK3CA). Interestingly, 32% of brain tumors had ≥1 ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations (P=0.019). Forty-eight percent of pts (320/670) had potentially actionable alterations; in 241, (75% of 320), by an FDA-approved drug (mostly off label). Illustrative examples of clinical utility will be presented such as a patient with gastric cancer and EGFRamplification in ctDNA who received anti-EGFR treatment (60% regression), as well a patient with aggressive gynecologic malignancy who received immunotherapy based on a hypermutated ctDNA profile. Conclusions: Most pts, including a subset of those with brain tumors, demonstrated ctDNA alterations. Pts with head and neck tumors harbored higher numbers of alterations. Overall, three quarters of pts with alteration(s) had ≥1 aberration that could potentially be pharmacologically tractable, suggesting the need to further assess the utility of ctDNA in a therapeutic setting. [Table: see text]

The impact of repeat-testing of common chemistry analytes at critical concentrations

Early notification of critical values by the clinical laboratory to the treating physician is a requirement for accreditation and is essential for effective patient management. Many laboratories automatically repeat a critical value before reporting it to prevent possible misdiagnosis. Given today’s advanced instrumentation and quality assurance practices, we questioned the validity of this approach. We performed an audit of repeat-testing in our laboratory to assess for significant differences between initial and repeated test results, estimate the delay caused by repeat-testing and to quantify the cost of repeating these assays.A retrospective audit of repeat-tests for sodium, potassium, calcium and magnesium in the first quarter of 2013 at Tygerberg Academic Laboratory was conducted. Data on the initial and repeat-test values and the time that they were performed was extracted from our laboratory information system. The Clinical Laboratory Improvement Amendment criteria for allowable error were employed to assess for significant difference between results.A total of 2308 repeated tests were studied. There was no significant difference in 2291 (99.3%) of the samples. The average delay ranged from 35 min for magnesium to 42 min for sodium and calcium. At least 2.9% of laboratory running costs for the analytes was spent on repeating them.The practice of repeating a critical test result appears unnecessary as it yields similar results, delays notification to the treating clinician and increases laboratory running costs.

Thymidylate Synthase as a Predictive Biomarker for Pemetrexed Response in NSCLC

In recent years, major strides in cancer research have made it possible to select personalized chemotherapy recommendations based on an individual patient’s tumor biology. The prognostic and/or predictive ability of biomarkers seeks to tailor the use of targeted chemotherapy and can result in improved clinical outcomes with reduced toxicity. A proliferation of new technology and pharmacotherapeutics in the setting of current FDA Clinical Laboratory Improvement Amendment (CLIA) standards has resulted in a recent surge in direct-to-physician biomarker tests. However, in the absence of clinical validation, there is the concern that the biomarkers may be utilized prematurely, resulting in improper chemotherapy selection and patient harm. Thymidylate synthase (TS) has been marketed as a predictive biomarker for the use of pemetrexed in NSCLC. We will examine the evidence behind the use of TS as a predictive biomarker to predict response to pemetrexed in NSCLC. At this time, the evidence does not currently support using TS assays to guide chemotherapy selection outside of a clinical research protocol.

Document Control Practices in 120 Clinical Laboratories

Context.—A variety of document control practices are required of clinical laboratories by US regulation, laboratory accreditors, and standard-setting organizations. Objective.—To determine how faithfully document control is being implemented in practice and whether particular approaches to document control result in better levels of compliance. Design.—Contemporaneous, structured audit of 8814 documents used in 120 laboratories for conformance with 6 generally accepted document control requirements: available, authorized, current, reviewed by management, reviewed by staff, and archived. Results.—Of the 8814 documents, 3113 (35%) fulfilled all 6 document control requirements. The requirement fulfilled most frequently was availability of the document at all shifts and locations (8564 documents; 97%). Only 4407 (50%) of documents fulfilled Clinical Laboratory Improvement Amendment requirements for being properly archived after updating or discontinuation. Policies and procedures were more likely to fulfill document control requirements than forms and work aids. Documents tended to be better controlled in some laboratory sections (eg, transfusion service) than in others (eg, microbiology and client services). We could not identify document control practices significantly associated with higher compliance rates. Conclusions.—Most laboratories are not meeting regulatory and accreditation requirements related to control of documents. It is not clear whether control failures have any impact on the quality of laboratory results or patient outcomes.