Amplifying the Voice of the Patient in Clinical Research: Development of Toolkits for Use in Designing and Conducting Patient-Centered Clinical Studies.

Incorporating patient perspectives into clinical studies is recognized as important to the development of high-quality, safe, and effective fit-for-patient medicines. However, no widely accepted methodology to help design more patient-centered studies has been established systematically. TransCelerate Biopharma Inc., a non-profit organization promoting collaboration across biopharmaceutical companies, organized a Patient Experience (PE) Initiative to create tools to intentionally include the patient perspective into the design and implementation of clinical studies. The resulting tools include the Patient Protocol Engagement Toolkit (P-PET), to engage patients early in protocol development, and the Study Participant Feedback Questionnaire (SPFQ), to assess patient experiences during clinical studies. To develop these toolkits, TransCelerate conducted a literature review and identified aspects of clinical studies that patients find either valuable or burdensome, or that affect participation, adherence, and engagement in a clinical study. The concepts identified were refined through elicitation of feedback from patient advisors, clinical study site advisors, and subject matter experts from member companies (MCs) of TransCelerate. This feedback was considered in identifying gaps, defining scientific methodology to understand how to evaluate patients' needs, and developing and refining the P-PET and the SPFQ. As part of the development process, descriptions/drafts of the tools were shared with patients, clinical site advisory groups, MCs, and the US Food and Drug Administration, and then revised. MCs simulated use of the tools, and feedback was incorporated into the final versions of the P-PET and SPFQ prior to public release. The P-PET and SPFQ are available free on the TransCelerate website.

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.