Characterizing Pain Points in Clinical Data Management and Assessing the Impact of Mid-Study Updates.

BACKGROUND: The causes, degree and disruptive nature of mid-study database updates and other pain points were evaluated to understand if and how the clinical data management function is managing rapid growth in data volume and diversity. METHODS: Tufts Center for the Study of Drug Development (Tufts CSDD)-in collaboration with IBM Watson Health-conducted an online global survey between September and October 2020. RESULTS: One hundred ninety four verified responses were analyzed. Planned and unplanned mid-study updates were the top challenges mentioned and their management was time intensive. Respondents reported an average of 4.1 planned and 3.7 unplanned mid-study updates per clinical trial. CONCLUSION: Mid-study database updates are disruptive and present a major opportunity to accelerate cycle times and improve efficiency, particularly as protocol designs become more flexible and the diversity of data, most notably unstructured data, increases.

Use of Mobile Devices to Measure Outcomes in Clinical Research, 2010-2016: A Systematic Literature Review.

BACKGROUND: The use of mobile devices in clinical research has advanced substantially in recent years due to the rapid pace of technology development. With an overall aim of informing the future use of mobile devices in interventional clinical research to measure primary outcomes, we conducted a systematic review of the use of and clinical outcomes measured by mobile devices (mobile outcomes) in observational and interventional clinical research. METHOD: We conducted a PubMed search using a range of search terms to retrieve peer-reviewed articles on clinical research published between January 2010 and May 2016 in which mobile devices were used to measure study outcomes. We screened each publication for specific inclusion and exclusion criteria. We then identified and qualitatively summarized the use of mobile outcome assessments in clinical research, including the type and design of the study, therapeutic focus, type of mobile device(s) used, and specific mobile outcomes reported. RESULTS: The search retrieved 2,530 potential articles of interest. After screening, 88 publications remained. Twenty-five percent of the publications (n = 22) described mobile outcomes used in interventional research, and the rest (n = 66) described observational clinical research. Thirteen therapeutic areas were represented. Five categories of mobile devices were identified: (1) inertial sensors, (2) biosensors, (3) pressure sensors and walkways, (4) medication adherence monitors, and (5) location monitors; inertial sensors/accelerometers were most common (reported in 86% of the publications). Among the variety of mobile outcomes, various assessments of physical activity were most common (reported in 74% of the publications). Other mobile outcomes included assessments of sleep, mobility, and pill adherence, as well as biomarkers assessed using a mobile device, including cardiac measures, glucose, gastric reflux, respiratory measures, and intensity of head-related injury. CONCLUSION: Mobile devices are being widely used in clinical research to assess outcomes, although their use in interventional research to assess therapeutic effectiveness is limited. For mobile devices to be used more frequently in pivotal interventional research - such as trials informing regulatory decision-making - more focus should be placed on: (1) consolidating the evidence supporting the clinical meaningfulness of specific mobile outcomes, and (2) standardizing the use of mobile devices in clinical research to measure specific mobile outcomes (e.g., data capture frequencies, placement of device). To that aim, this manuscript offers a broad overview of the various mobile outcome assessments currently used in observational and interventional research, and categorizes and consolidates this information for researchers interested in using mobile devices to assess outcomes in interventional research.

The effect of ranitidine on the pharmacokinetics of rosiglitazone in healthy adult male volunteers.

BACKGROUND: Rosiglitazone is an insulin-sensitizing oral agent in the thiazolidinedione class used to treat patients with type 2 diabetes mellitus. It binds to peroxisome proliferator-activated receptor gamma in liver, muscle, and adipose tissue. Ranitidine, a histamine2-receptor antagonist, may be prescribed for patients with type 2 diabetes and esophageal symptoms such as heartburn. By raising gastrointestinal pH levels, ranitidine may affect the bioavailability of coadministered drugs. OBJECTIVES: This article presents the absolute bioavailability of rosiglitazone, as well as the effects of ranitidine on the pharmacokinetics of rosiglitazone. METHODS: Healthy men were enrolled in a randomized, open-label, 4-period, period-balanced crossover study of rosiglitazone and ranitidine. All individuals received each of 4 regimens successively, separated by a 4-day washout period: a single IV dose of rosiglitazone 2 mg administered alone over 1 hour; a single IV dose of rosiglitazone 2 mg administered over 1 hour on the fourth day of treatment with oral ranitidine 150 mg given every 12 hours; a single oral dose of rosiglitazone 4 mg alone; and a single oral dose of rosiglitazone 4 mg on the fourth day of treatment with oral ranitidine 150 mg given every 12 hours. The primary end point was dose-normalized area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)). Maximum observed plasma concentration (Cmax), the time at which Cmax occurred (Tmax), plasma clearance (CL), steady-state volume of distribution (Vss), and terminal elimination half-life (t 1/2) were also assessed. RESULTS: Twelve individuals were enrolled. The absolute bioavailability of rosiglitazone was 99%. For AUC(0-infinity), the point estimate and the associated 95% CI for the ratio of ranitidine + IV rosiglitazone to IV rosiglitazone alone was 1.02 (range, 0.88-1.20). With oral rosiglitazone, the AUC(0-infinity) point estimate (95% CI) for the ratio of ranitidine + rosiglitazone to rosiglitazone alone was 0.99 (range, 0.85-1.16). Cmax, Tmax, t 1/2, Vss and CL of rosiglitazone, whether administered orally or intravenously, were unaffected by ranitidine. Oral and IV rosiglitazone were associated with a favorable safety profile and were well tolerated with or without concurrent ranitidine treatment. CONCLUSIONS: In this study of 12 healthy adult male volunteers, the absolute bioavailability of rosiglitazone was 99%, and the oral and IV single-dose pharmacokinetics of rosiglitazone were unaltered by concurrent treatment with ranitidine.

Investigation of the interaction between argatroban and acetaminophen, lidocaine, or digoxin.

The potential pharmacokinetic interactions between argatroban and acetaminophen, lidocaine, or digoxin were examined. Three randomized crossover studies were conducted. In the first study, 11 subjects completed three sessions (with a five-day washout period between sessions), receiving two 500-mg acetaminophen caplets at 0, 6, 12, 18, and 24 hours; i.v. argatroban 1.5 micrograms/kg/min from hours 12 to 30; or a combination of both. In the second study, 12 subjects completed three sessions (with a five-day washout period between sessions), receiving lidocaine hydrochloride injection 2 mg/kg/hr for 16 hours (after receiving a loading dose of 1.5 mg/kg over 10 minutes), i.v. argatroban 1.5 micrograms/kg/min for 16 hours, or a combination of both. In the third study, 12 subjects completed two sessions (with a seven-day washout period between sessions), receiving oral digoxin 0.375 mg/day for 15 days and either i.v. placebo or argatroban 2 micrograms/kg/min on days 11 through 15. Primary pharmacokinetic values in each study included area under the drug concentration versus time curve and steady-state concentrations of argatroban and the concomitantly administered drug. Lack of a pharmacokinetic interaction (individually defined for each study) was demonstrated in each study. Argatroban, regardless of acetaminophen or lidocaine administration, prolonged activated partial thromboplastin time values approximately 1.6-1.8 times the baseline values. No deaths, unexpected adverse events, or clinically significant changes in safety laboratory values occurred. No pharmacokinetic interaction was detected between argatroban and acetaminophen, lidocaine, or digoxin. Argatroban is well tolerated during coadministration with these drugs. In practice, argatroban coadministered with these frequently prescribed drugs should require no dosage adjustments.