INSTRuCT: Protocol, Infrastructure, and Governance

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/ ; Unique Identifier: CTRI/2017/05/008507.

The TIME Trial Network to facilitate rapid clinical trial activation, patient screening, and enrollment in molecularly targeted trials.

1563 Background: Clinical trials that require patients to have specific actionable mutations based on next generation sequencing (NGS) present unique problems, such as recruiting patients with rare mutations, low enrollment rates, and distance between patients and trial sites. Such barriers can slow the pace of trial enrollment and delay the development of new therapeutic options. Methods: Tempus Labs has partnered with experienced research sites and pharmaceutical companies with molecularly targeted clinical trials to create the TIME Trial Network. The study portfolio includes pharmaceutical sponsored phase I-III clinical trials across solid tumors and hematological malignancies, targeting actionable mutations. This network was established to ensure rapid just-in-time (JIT) activation of trials by streamlining start-up activities (i.e., execution of CTAs and study budgets/financial exhibits, regulatory paperwork, SIV planning and conduct, drug and study supply shipments, submission to the central IRB, and sponsor-specific requirements). Rapid activation begins upon receipt of an activation form from a site partner. “Site Activated” describes a site that has fulfilled all regulatory, documentation, contracting requirements, and has sponsor approval to screen and enroll patients. Results: In Q4 2020, JIT activations were completed for 6 unique interventional clinical trials across 10 sites in 8 US states in the TIME Trial Network. On average, sites were activated in 9.4 business days. Patients enrolled had rare NGS mutations and were from geographically diverse locations. In one urgent case, trial activation, patient consent, screening, and treatment were achieved in 5 business days. In total, 91.7% of patients consented to trial. The average timeline from activation to consent was 4.5 days (range 0 - 24 days), with half of patients consenting within 1 business day. 45.5% of patients who consented to trial received the study drug within 1 day of consent; 2 patients dosed on day of consent. Conclusions: Over a 3-month period, on average, TIME Trial sites were activated in 9.4 days (compared to the 20+ week industry-wide average), and patient consent was completed in 4.5 days. Rapid JIT activations through the TIME program provide significant improvements in trial enrollment timelines and increase access to therapies nationwide. JIT activations may be especially useful for rural, underserved communities, as sites can enroll diverse patient populations and help address the equity gap in clinical trials across ethnic groups.[Table: see text]

Conducting clinical trials during the COVID-19 pandemic—a collaborative trial network response

The unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond.

Clinical Trials Evaluating Proton Therapy

Although proton therapy was developed almost 80 years ago, widespread clinical implementation has been limited until the past decade. With the growing use of proton therapy, there is a desire to prove the equivalence or superiority of proton therapy across a number of cancer disease sites. Dozens of clinical trials have been developed to accomplish this within individual institutions, among a few centers, and across national and international networks such as the National Cancer Institute’s National Clinical Trial Network. The protocols include proton therapy imbedded in trials with photon therapy as well as randomized photon vs. proton trials. This chapter provides an overview of the design of such trials as well as some of the challenges facing protocols with proton therapy.