Digitizing clinical trials.

Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a "digital clinical trial" involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research.

Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study.

BACKGROUND: There are no currently approved methods for the screening and early detection of lung cancer. We compared the ability of conventional white-light bronchoscopy (WLB) and laser-induced fluorescence endoscopy (LIFE) to detect preneoplastic lung lesions in a randomized trial in which both the order of the procedures and the bronchoscopists were randomly assigned. METHODS: The study included high-risk subjects enrolled because of a cigarette smoking history of at least 30 pack-years, an air-flow obstruction, and either an abnormal sputum cytology (n = 48) or a previous or suspected lung cancer (n = 7). LIFE and WLB were performed on all patients. Biopsy specimens were assessed for histologic abnormalities, including the presence of angiogenic squamous dysplasia. All statistical tests were two-sided. RESULTS: A total of 391 biopsy specimens were taken from the 55 patients. Thirty-two patients (58%; 95% confidence interval [CI] = 44% to 71%) had at least one biopsy with moderate or severe dysplasia, and 19 (59%; 95% CI = 41% to 76%) of these patients could be diagnosed based solely on the results of LIFE. LIFE was statistically significantly more sensitive than WLB for detecting moderate dysplasia or worse (68.8% versus 21.9%, respectively) (difference = 46.9%; 95% CI = 25% to 68%; P< .001). The relative sensitivities (WLB = 1.0) were 3.1 (95% CI = 1.6 to 6.3) for LIFE and 3.7 (95% CI = 1.9 to 7.3) for LIFE and WLB combined. LIFE was less specific than WLB (69.6% versus 78.3%, respectively; P = .45), but the difference was not statistically significant. The relative specificities (WLB = 1.0) were 0.9 for LIFE (95% CI = 0.6 to 1.3) and 0.6 (95% CI = 0.4 to 1.0) for LIFE and WLB combined. The results were similar regardless of the order of the procedures or the order of the bronchoscopists. Also, LIFE was better at identifying angiogenic squamous dysplasia lesions than WLB (detection ratio [DR], which indicates the relative likelihood of getting a positive result in a sample with dysplasia compared with one without, for LIFE = 1.39 [95% CI = 1.17 to 1.65] versus DR for WLB = 0.67 [95% CI = 0.38 to 1.21]). CONCLUSION: LIFE was more sensitive than WLB in detecting preneoplastic bronchial changes in high-risk subjects. The prognostic implication of this finding is not yet clear.

Patient age and cancer treatment decisions. Patient and physician views.

PURPOSE: The purpose of this study was to examine patient and physician factors influencing the decision to use adjuvant chemotherapy for stage III colon cancer in elderly persons. DESCRIPTION OF STUDY: A cross-sectional mailed population-based survey of patients 65 years of age and older who had undergone surgical resection of stage III colon cancer in Colorado between August 1995 and December 1997 were identified by the statewide cancer registry (n = 276) and their treating physicians (n = 232). A questionnaire about the determinants of colon cancer treatment decisions was mailed to all patients for whom physician permission was granted (n = 119). A similar questionnaire was sent to treating physicians. RESULTS: Ninety-two physicians (internal medicine 23%; family medicine 12%; surgery 37%; and oncology 24%) and 67 patients (mean age 75.8 years; 55% women) completed surveys. Fifty-four (80.6%) of the patients had received adjuvant chemotherapy. The major determinants of receiving adjuvant chemotherapy were having seen an oncologist (P = .003), being younger (P = .003), and being married (P = .021). After controlling for other potential influences, only having seen an oncologist (odds ratio 8.0; confidence interval 1.5-43.1) remained significantly associated with the receipt of chemotherapy. Physicians were more likely than patients to rank comorbid conditions (39.1% versus 3.0%, respectively; P < .001) and the medical literature (20.7% versus 4.5%, respectively; P = .004) as important factors in making treatment decisions, while patients were more likely than physicians to rank physician opinion (73.1% versus 26.1%, respectively; P = .001), family preference (31.3% versus 9.8%, respectively; P = .001), and family burden (10.4% versus 2.2%, respectively; P = .038). CLINICAL IMPLICATIONS: In this elderly population, patient age is not recognized by patients or physicians as affecting the decision to use adjuvant chemotherapy. Other biologic and social factors are important, however, and the perspectives of physicians and patients differ regarding their relative importance.

Diffuse alveolar hemorrhage with underlying pulmonary capillaritis in the retinoic acid syndrome.

All-trans-retinoic acid (ATRA) can induce a clinical remission in patients with acute promyelocytic leukemia. An adverse condition called "retinoic acid syndrome" limits this therapy. It is characterized by fever and respiratory distress, along with weight gain, pleural or pericardial effusions, peripheral edema, thromboembolic events, and intermittent hypotension. The lung disease has been previously ascribed to an infiltration of leukemic or maturing myeloid cells into lung parenchyma, which is sometimes associated with pleural effusions and diffuse alveolar hemorrhage. We report a case of retinoic acid syndrome in an 18-yr-old woman who developed diffuse alveolar hemorrhage while being treated with ATRA for acute promyelocytic leukemia. An open lung biopsy revealed pulmonary capillaritis.

Anaphylactoid reaction with suramin.

Suramin, a drug used to treat parasitic diseases, is currently being investigated as a treatment for metastatic prostate cancer. A 73-year-old man had an anaphylactoid reaction following the first dose of suramin. It was treated successfully with epinephrine, diphenhydramine, and hydrocortisone. Investigators should be aware of the possibility of such a reaction with parenteral administration of this drug.