Fall 2021: Clinician Investigator Trainee Association Of Canada (CITAC)

I hope you’re taking care and found some time to relax this summer. A new semester may mean a big transition—some folks are starting their graduate studies, re-entering clerkship, starting residency or entering a fellowship. For some, there will be little or no change at all; but just a continuation of one of the many phases of the physician-scientist training pathway. Whatever stage you’re at, the Clinical Investigator Trainee Association of Canada (CITAC) community is here to support and advocate for you!

Practical Psychopharmacology

Despite the lack of guidance available for practitioners, extensive polypharmacy has become the primary method of treating patients with severe and chronic mood, anxiety, psychotic or behavioral disorders. This ground-breaking new book provides an overview of psychopharmacology knowledge and decision-making strategies, integrating findings from evidence-based trials with real-world clinical presentations. It adopts the approach and mind-set of a clinical investigator and reveals how prescribers can practice 'bespoke psychopharmacology', tailoring care to the individualized needs of patients. Practitioners at all levels of expertise will enhance their ability to devise rationale-based treatments, targeting manifestations of dysfunctional neural circuitry and dimensions of psychopathology that cut across conventional psychiatric diagnoses. Presented in a user-friendly, practical, full-colour layout and incorporating summary tables, bullet points, and illustrative case vignettes, it is an invaluable guide for all healthcare professionals prescribing psychotropic medications, including psychiatry specialists, primary care physicians, and advanced practice registered nurses.

Supporting the Development of Physician-scientists

In the last decade, there has been a discrepancy between the increasing recognition for research involvement in medical training and the stagnation in the number physician-scientists. Health research funding cutbacks, inadequate mentorship, heavy schedules, and unfamiliarity with scientific methodology are obstacles that limit research interest amongst junior medical learners and cause attrition of promising physician-scientist in training. This article outlines five strategies to promote and facilitate the development of physician-scientists with the understanding that research is integral to clinical excellence. Some of the ways the undergraduate and postgraduate medical curricula can better lend themselves to producing clinicians with the skillset to address clinical uncertainties through an evidence-based approach are: partnerships between healthcare and academia, increasing admission to MD/PhD and Clinical Investigator programs, establishing fundamentals of scientific thinking, long-term research mentorship, facilitating knowledge translation.

Spring 2021: Clinician Investigator Trainee Association Of Canada (CITAC)

The Clinician Investigator Trainee Association of Canada (CI) trainees across the country around the common goal of improving training conditions for those pursuing a career at the junction of research and medicine. Since then, the CI training landscape has shifted dramatically. The number of Canadian CI trainees enrolled totaling 289 MD-PhD trainees and 389 Clinical Investigator Program (CIP) trainees as of 2019 [1]. Alumni outcome data have presented conclusive evidence that MD-PhD training programs are effective in producing CI careers [2–4].

Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia after Same-Day Dosing of Eflapegrastim in Patients with Breast Cancer Receiving Docetaxel and Cyclophosphamide (NCT04187898)

Background: Eflapegrastim (Rolontis®, Efla) is a long-acting granulocyte-colony stimulating factor (G-CSF), consisting of a recombinant human G-CSF analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. Efla is not a biosimilar and represents the first myeloid growth factor innovation in more than 15 years. In preclinical studies with chemotherapy-induced neutropenic rats, Efla showed ~3-fold higher exposure in serum and higher exposure in bone marrow at similar doses compared to pegfilgrastim (Peg). The duration of neutropenia (DN) was shown to be significantly shorter with Efla vs Peg when administered on the same day or 24-hours post-chemotherapy. Additionally, the DN after Efla administered on the same day as chemotherapy was similar to the DN 24 hours post-chemotherapy. Moreover, in two Phase 3 studies that randomized a total of 643 patients with early-stage breast cancer (ESBC) to either Efla (3.6 mg G-CSF n=314) or Peg (6 mg G-CSF n=329) given ~ 24 hours after docetaxel and cyclophosphamide (TC), the duration of severe neutropenia (DSN) was statistically noninferior in patients treated with Efla compared to Peg. As a standard of practice, G-CSF products require administration 24 hours after chemotherapy. Since Efla preclinical and clinical results suggest that the increased activity of Efla may provide effective prophylaxis against chemotherapy-induced neutropenia when administered on the same day as chemotherapy, the purpose of this study is to assess the feasibility of giving Efla same-day (at 3 different dosing timepoints) in patients receiving TC for the treatment of ESBC. Study Design and Methods : This is a randomized, schedule finding, multicenter, Phase 1, open-label study evaluating the same-day administration of 13.2 mg/0.6 mL Efla following IV infusion of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) in patients with ESBC. Treatment: On Cycle 1, Day 1, patients will be randomized 1:1:1 to Efla dose administration schedules of 0.5, 3, and 5 hours after TC. In Cycles 2-4, Efla will be administered ~ 24 hours following the administration of TC for all treatment arms. Clinical Endpoints: The primary endpoint is DSN (ANC <0.5×109/L) in Cycle 1. The secondary endpoints for Cycle 1 administration include the incidence of SN, time to recovery from SN, incidence of Grade 3 febrile neutropenia, incidence of neutropenic complications, and pharmacokinetics (PK) of Efla. Blood for hematology will be drawn daily for the first 10 days and then on Day 1 of Cycles 2-4. Inclusion Criteria: This study is enrolling histologically confirmed (operable stage I-IIIA) patients with ESBC, who are >18 years of age, are candidates for neoadjuvant or adjuvant TC, have an ECOG of <2, with adequate hematological, renal, and hepatic function. Exclusion Criteria: Patients will be excluded if they have an active or concurrent malignancy, or locally recurrent/metastatic or bilateral breast cancer, a life-threatening disease, a known sensitivity or previous reaction to E. coli derived products, exposure to a G-CSF agent within 3 months, history of bone marrow or hematopoietic stem cell transplant, radiotherapy or surgery within 30 days, are pregnant or are breast-feeding. Statistical Methods: A sample size of 15 patients per dosing schedule arm was determined to provide adequate precision for the 95% CI of the DSN and secondary endpoints, including PK parameters, assuming a standard deviation of 1.0 days based on the prior studies. A safety evaluation will be performed once the first three patients in each arm have completed Cycle 1. Target Accrual: 45 patients (15 subjects/arm). Enrollment began in April 2020. Disclosures Schwartzberg: Spectrum Pharmaceuticals, Inc.: Consultancy, Other: clinical investigator for trial. Francis:Spectrum Pharmaceuticals, Inc.: Other: clinical investigator for trial. Osama:Spectrum Pharmaceuticals, Inc.: Other: clinical investigator for trial. Modiano:Spectrum Pharmaceuticals, Inc.: Other: clinical investigator for trial. Bharadwaj:Spectrum Pharmaceuticals, Inc.: Other: clinical investigator for trial. Chawla:Spectrum Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Bhat:Spectrum Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Lebel:Spectrum Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Tchekmedyian:Spectrum Pharmaceuticals, Inc.: Other: clinical investigator for trial.

Ethics of RCTs

Equipoise is defined by Freedman (1987: 141) as a “state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial.” This principle is grounded in the ethical motivation that any ex-ante preference for a given option would undermine the interests of those who are offered another. Randomized controlled trials (RCTs) in development economics disregard the equipoise requirement by typically disadvantaging the control group. This chapter investigates how the equipoise principle is formalized in the medical literature and discusses whether and how it should be taken into consideration by economists. It argues that equipoise is especially relevant when double (or even single) blindness is excluded and when the control group includes already vulnerable individuals. More generally, this chapter advocates for developing a vibrant ethics conversation on the design and fairness of RCTs in social sciences.

Treatment of 52 patients with a self-adhesive siliconised superabsorbent dressing: a multicentre observational study

Objective: To provide ‘in use’ clinical data to support exudate management in patients with moderately to highly exuding wounds with bordered superabsorbent wound dressing with a silicone adhesive interface. Method: This study was an open-labelled non-comparative study. Patients included in the study were selected by the clinical investigator(s) according to whether the patient required a dressing for the management of moderately to highly exuding wounds. Results: The primary aim of this study was to evaluate the clinical objective in relation to exudate handling (moderate to high) with a superabsorbent silicone border dressing (Zetuvit Plus Silicone Border; SAP silicone border dressing; designated RespoSorb Silicone Border in some countries). The SAP border dressing had met the clinical objectives relating to exudate management, affirmed by the health professionals with a yes response in 94% of cases. Additionally, the health professionals rated the handling of exudate as excellent/good (78%) and most (80%) reported that they would use the SAP silicone border dressing again. Allied to this was the fact that the SAP silicone border dressing improved the wound edge and periwound skin conditions (29% and 36% of patients, respectively). Regarding dressing retention, the SAP silicone border dressing retained its position in 72% of patients. For wear time, the largest proportion of dressing changes, both pre-study and during the evaluation period, was every third day (45% and 44%, respectively). But there was a shift to extended wear time with use of the SAP silicone border dressing with 72% of patients' dressing changes being every third day or longer. Conclusion: The SAP silicone border dressing was successful in managing wound exudate in moderately to highly exuding wounds and consequently this had a beneficial impact on the wound edge and periwound skin. Overall, there was a positive effect on wound bed preparation and in turn the healing response was progressive. This study has shown that the SAP silicone border dressing successfully controlled exudate and provided positive benefits when used in the treatment of patients with moderately to highly exuding wounds.