In the early 2000’s, when the drug Gleevac1 was first approved by the Food and Drug Administration (FDA)2, a new era of precision medicine was born. With it, the pharmaceutical industry experienced a major increase in the amount of research data being produced by clinical trials. The volume of data required for regulatory submissions from genomic-based studies facilitated a new way of managing data acquisition, analysis and sharing.
Today, an even greater amount of data is required for the drug approval process, creating another regulatory shift for pharmaceutical organizations and investigators. In addition, the rush to defend against the “Pandemic of 2020” has also presented new challenges for seamless data collection. The good news, however, is new technologies are being developed to help alleviate these problems, which means more efficient therapeutic workflows for timely FDA approval. The following examines how the approval process can be enhanced in order to ensure better outcomes for both pharmaceutical companies and the patients they serve.
Change is needed
For many years, the FDA has provided guidance3 in response to the changing landscape within the drug development environment, and has recently created several new study designs (i.e., platform trials, basket or bucket trials, umbrella trials and adaptive trials) to make investigations more data-friendly for clinical investigators. This new view was designed so that trial participants would become more involved in the clinical studies. However, logistical hurdles have made the completion of some trials a daunting task. These obstacles have only reiterated and intensified the calls for standardizing clinical trial start-ups, implementations, and closeout processes to ensure successful outcomes for promising drug candidates.
The scientific urgency of implementing a new strategic drug development framework was made quite clear in early 2019, when Dr. Scott Gottlieb4, the outgoing Commissioner of the FDA, put pressure on the biopharmaceutical industry for delaying the adoption of innovative approaches to clinical trial development. Gottlieb stated that outdated business practices (i.e., legacy business models that discourage collaboration and data sharing) and “Kabuki drug pricing” were to blame. He asserted that immediate changes were needed to streamline the clinical trial process, or there would be a continued delay in opportunities for commercialization of important products in the drug development pipeline.
In answer to this, in 2020, the federal government orchestrated one of most aggressive Public-Private-Partnerships5 ever forged. The government, big pharma, and academia came together via an economic/scientific/political framework known as Operation Warp Speed6 (OWS). OWS was initiated to fast track the COVID-19 vaccine’s commercial readiness and to organize the best intellectual minds in medicine around the world. The partnership also helped to encourage unprecedented scientific collaboration with an infusion of significant capital resources, which shed light on key areas that would transform the drug development industry.
The evolution of a more data-driven approach
A survey published by the Pharmaceutical Research and Manufacturers of America (PhRMA)7 stated that in 2017 the pharmaceutical industry’s R&D investments increased to $71.4bn, up from $29.8bn in 2001. However, the number of FDA drug approvals8 only grew slightly, and was nowhere proportional to the increase seen in R&D spending9. The caveat of this disparity is that money isn’t the root cause for the industry’s inability to deliver timely therapeutics to the healthcare marketplace. The problem is with the process, and this is where analytical tools can help bridged the gap by providing shortened development timelines, reduced cost and increased patient involvement in recruitment and day-to-day protocol procedures.
In 2018, the Center for Drug Evaluation and Research (CDER)10 at the FDA launched a pilot feasibility program to improve clinical information gathering, which is key to making drug approval decisions. In 2020, the program identified11 significant inefficiencies in the drug development process and suggested several areas of changes. P360 also conducted a review of the drug development industry, and discovered that 75% of studies have no integration tools and rely on manual data entries that produce disjointed workflows that are more prone to mistakes. Solutions like P360’s Trials360 simplify clinical study workflow by streamlining data management, improving productivity with adaptable capabilities across all phases of the clinical trial process.
Innovative companies like P360, headed by CEO and Founder Anupam Nandwana, have answered the latest drug development call-to-action by providing simple solutions for pharmaceutical organizations and contract research organizations (CROs) with commercial-ready technology via its Trials360 platform. By delivering a 360⁰ industrial vantage point from big pharma, the prescriber, the investigator, and the patient, their advanced technologies have been able to improve the level of analytical efficiency compared to the traditional clinical trial model. Trials360 deploys capabilities that ensure the highest returns on data management, trial documentation, and patient involvement.
One of the logistical goals of P360 is to break down clinical trial work silos and expand the workflow efficiency of multi-centered trials conducted across the globe. The results of such novel work by multi-national studies were recently on display by the RECOVERY Trial12 and the ACTT-1 study group13, which published their highly anticipated findings in the New England Journal of Medicine (NEJM) and the Journal American Medical Association (JAMA). This work, undertaken in 2020 by multiple hospitals in multiple countries (United States, Denmark, United Kingdom, Greece, Spain, Japan, Germany, Mexico, and Singapore) to investigate the efficacy of Dexamethasone14 and Remdesivir15 in COVID-19 patients, was probably the most critical therapeutic findings achieved by a global collaborative effort in the last decade. This is testament to the urgent need for more advanced technology that will reduce silo-style clinical research – in favor of data sharing, integrated planning, and commercial-readiness offered by Trials360.
Technology can increase clinical trial participation
The simplification of clinical study start-ups and site activation, which might take up to 8 months from pre-visit to site initiation, and up to 8 weeks to complete feasibility questionnaires, will greatly help leverage the centralization of databases for investigators. Trials360 can deploy and manage multiple programs across multiple geographies, identify and recruit the right trial subjects, track visits, and monitor progress with an integrated dashboard. The analysis synchronizes data management across CTMS, EDC, eTMF and enable trials to meet Federal Sunshine Reporting Data16 requirements, thereby reducing time, cost, and data inconsistency.
Up to 50% of a clinical trial cost is spent on site monitoring, and 35% of inspections have delays because Trial Master files (TMF) are incomplete or not readily available. Trials360 reduces complexity and risk with a single, unified platform for all study data and processes to improve readiness and compliance for site visit reports. In terms of financial management, 60% of sites use manual financial processes and are unprepared to manage growing payment volumes and complexity. Trials360 also track study financials, integrate financial planning, sponsor budget monitoring, and create reporting modules, from start to finish.
Clinical trials historically fail to meet scientific expectations because of several key barriers that can be overcome with the use of innovative technology. About 18% of clinical trial participants drop out of their current clinical studies and usually suggest two key factors: financial hardship and scheduling conflicts. Decentralized trials have been used to remove such obstacles, but such efforts also require the use of a smartphone, knowledge of mobile technology and a reliable Internet connection. All of which might increase the burden for some participants, particularly in the economically challenged regions and the elderly communities.
One long-held belief about clinical trial participants is that there is a significant concern regarding the risk-benefit of using their study-sensitive information. Although there is little in the medical literature of such perceptions, a recent article published in the NEJM17 by investigators at Stanford University School of Medicine, suggest results to the contrary. A total of 93% of respondents stated that they were very (69%) or moderately (24%) likely to allow their clinical trial data to be shared with investigators at universities or other not-for-profit organizations. Where only 4% were very or somewhat unlikely to share their information. Such results express real optimism and the potential impact innovative technology, like Trials360, can offer clinical trial participants regarding information security and transparency.
The future in now
The modernization of the drug approval process will be achieved with the help of regulatory agencies from around the world. In 2019, the FDA approved 48 novel drugs18 which was the result of 46,391 participants in clinical trials, and of which 60% of the subjects were located outside the United States. In 2020, there were 53 novel drugs19approved by the FDA. The future of more robust therapeutics rest in our regulatory apparatus’s willingness to upgrade established policies and put forth best practices identified globally as the biopharmaceutical industry continues to embrace new ideas for solving old investigative problems.
The goal of P360 is to develop the most innovative commercial tools to help in the drug pipeline transformation and make solving such problems much easier. The unforeseen barriers of the past (i.e., scientific, logistical, or social) which have prolonged the drug approval process for decades, should no longer preclude the adoption of novel solutions offered by Trials360 which can produce useful therapeutic products for the consumer marketplace.
Kenyatta Cosby, MD
ABOUT THE AUTHOR
Dr. Cosby is a contributing freelance medical writer based in Rockville, Maryland, U.S.A. He is a Physician Scientist who received his medical degree from Howard University College of Medicine and research training at the National Heart Lung Blood Institute/National Institutes of Health and Johns Hopkins University School of Medicine. He successfully managed an FDA-approved clinical trial, featured in the New York Times (https://www.nytimes.com/2003/11/03/us/study-finds-that-nitrites-in-the-body-greatly-aid-blood-flow.html) and published the manuscript in the journal, Nature Medicine (https://www.nature.com/articles/nm954). He also writes on many other topics (i.e., Surgery, Diabetes, Oncology, Hematology, Cardiovascular Research, Imaging, Mental Health Disorders, and Cardiology).
20: Benkeser D, Díaz I,Luedtke A, Segal J, Scharfstein D, Rosenblum M. Improving precision and power in randomized trials for COVID- treatments using covariate adjustment, for binary, ordinal, and time-to-event outcomes. Biometrics. 2020;115.
21: https://www.fda.gov/media/137926/download– COVID-19: Developing Drugs and Biological Products for Treatment or Prevention Guidance for Industry
22: https://www.fda.gov/media/123801/download- Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics with Continuous Outcomes Guidance for Industry
24: COVID-19 treatment guidelines. Bethesda, MD: National Institutes of Health, 2020 (https://www.covid19treatmentguidelines.nih.gov/dexamethasone/).
25: Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020; 395:1569-1578.
26: Mello M, Lieou V, and Steven N. Goodman. Clinical Trial Participants’ Views of the Risks and Benefits of Data Sharing. N Engl J Med 2018; 378:2202-2211. June 7, 2018.
27: RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med. 2020 Jul 17: PMID: 32678530; PMCID: PMC7383595.
28: ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 – Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. PMID: 32445440; PMCID: PMC7262788.