Dr. Harsha K Rajasimha, MS, Ph.D. – Founder, Jeeva Informatics Solutions Inc.; Co-Authored by Dr. Padma Rammoorthy.
In 1820, a group of physicians, driven by concerns regarding the quality and reliability of medicines, set up and released the first United States Pharmacopeia (USP). This pioneering publication included formulas for preparing 217 drugs deemed the most extensively researched and comprehended during that period.1 In 1906, the original Food and Drug Act was passed by Congress. The foundation of the FDA's current regulatory functions can be traced back to this act, which prohibited the interstate trade of adulterated and misbranded food and drugs. Although the agency was not officially named the FDA until 1930, this pivotal law marked the beginning of the FDA's modern regulatory efforts. Over the course of the century, the FDA has implemented multiple safeguards to assess and approve investigational new drugs.2,3
Various Phases of the Drug Approval Process
In the early stages of preclinical development for a new drug, the primary objective of the sponsor is to assess the product's safety profile for initial human use and evaluate its pharmacological activity to justify further development. Once a product is identified as a potential candidate, the sponsor shifts their focus towards gathering the required data and information to demonstrate that the product poses minimal risks to humans in limited, early-stage clinical studies. The role of the FDA becomes significant at this stage, as the product transitions into an Investigational New Drug (IND).
Any investigational drug undergoes a three-phase process before potential approval for commercial use. After submitting the IND application, the sponsor must observe a 30-day waiting period during which the FDA reviews the IND to ensure the safety of research subjects. Clinical trials then commence, marking the drug's initial testing on humans. These clinical trial phases evaluate the drug's dosage, safety, and efficacy.
Phase one which can last for several months, involves testing the IND on 20 to 100 healthy volunteers or individuals with a specific disease or condition. This phase primarily focuses on safety and dosage. Around 70% of drugs progress to Phase Two. In Phase 2, several hundred participants are involved, providing further safety data. Phase 2 duration ranges from several months to up to two years, with approximately 33% of drugs advancing to the next phase.
The last crucial stage preceding drug approval is Phase 3. In this phase, researchers conduct studies to determine whether the product provides a treatment benefit to a specific population. Phase 3 involves a larger participant pool of 300 to 3,000 individuals. The duration of Phase 3 can vary from 1 to 5 years, and the drug approval rate at this stage is approximately 25%.4
The overall process of drug development leading to final approval involves navigating numerous challenges and adhering to regulatory requirements. It typically spans several years, reflecting the complexity and rigor involved in bringing a new drug to market.
The process of discovering and developing a new drug is time consuming, expensive, and carries inherent risks. In a competitive market, small pharmaceutical companies may face challenges and potential delays in bringing a new drug to market. According to Deloitte, the average cost of developing a new drug among the top 20 global biopharmas it studied rose 15% ($298 million) last year, to approximately $2.3 billion.5 However, they can mitigate these obstacles by carefully analyzing and addressing the major risk factors associated with conducting a successful clinical trial.
Studies indicate that a key determinant of a successful clinical study is to efficiently recruit and retain an adequate number of the study population. Finding and enrolling a sufficient number of eligible participants within the desired timeframe can be challenging. Strict inclusion and exclusion criteria, limited awareness among potential participants, and logistical barriers may contribute to recruitment difficulties. Globally, more than 80% of trials fail to enroll on time resulting in an extension of study and or the addition of new study sites.6 Similar to enrollment is the retention of patients and ensuring participants adhere to the trial protocol and remain engaged throughout the study duration. This is crucial for generating reliable data.
But patient recruitment and retention can be challenging due to various factors like:
- Participant lack of motivation
- Logistic burdens for the participants to travel to the sites
- Interference with work commitments or family responsibilities
- Lack of patient engagement
leading to patient dropouts. This can cause substantial delays and impose significant financial burdens on trial sponsors.
One solution which can address the above issues are Decentralized Clinical Trials.
The COVID-19 pandemic has necessitated the widespread adoption of technology in various aspects, including clinical trials. This has led to the emergence of decentralized clinical trials (DCT), which encompass remote screening, enrollment, e-consent, patient engagement, and ePRO (patient-related outcome) measures.
Small and medium-sized biopharmaceutical companies can leverage decentralized clinical trial platforms for their clinical trials. By utilizing such platforms, these companies can benefit from accelerated remote pre-screening, e-consent processes, and efficient referral to enrollment sites. Patients can be actively engaged through various digital means like email, SMS prompts, audio, and video messages. Tele-visits can offer a solution to alleviate travel burdens. Additionally, the use of reusable cloud infrastructure and automation can minimize manual and repetitive tasks, streamlining trial operations.
Clinical trials can be resource-intensive and costly endeavors. Securing sufficient funding, managing trial budgets, and allocating resources effectively are ongoing challenges, particularly for small and medium-sized companies with limited funding opportunities. Leveraging technology for patient recruitment, constant engagement to prevent patient dropout, minimizing site visits, and streamlining data collection and monitoring can help overcome some of the persistent challenges faced by trial sponsors.
References
- “What is a Pharmacopeia? | Quality Matters | U.S. Pharmacopeia Blog.” USP - Quality Matters, 7 August 2014, https://qualitymatters.usp.org/what-pharmacopeia. Accessed 14 July 2023.
- “FDA History.” FDA, 29 June 2018, https://www.fda.gov/about-fda/fda-history. Accessed 14 July 2023.
- “A History of the FDA and Drug Regulation in the United States.” FDA, https://www.fda.gov/ files/drugs/published/A-History-of-the-FDA-and-Drug-Regulation-in-the-United-States. pdf. Accessed 14 July 2023.
- “Investigational New Drug (IND) Application.” FDA, https://www.fda.gov/drugs/types applications/investigational-new-drug-ind-application. Accessed 14 July 2023.
- “Pharma R&D return on investment falls in post-pandemic market.” Deloitte, 9 January 2023, https://www2.deloitte.com/uk/en/pages/press-releases/articles/pharma-r-d-return on-investment-falls-in-post-pandemic-market.html. Accessed 14 July 2023.
- Desai, Mira. “Recruitment and retention of participants in clinical studies: Critical issues and challenges.” NCBI, 6 May 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342339/. Accessed 14 July 2023.
Dr. Harsha Rajasimha is the founder and CEO of Jeeva Informatics Solutions, based in Virginia. The personal experience of losing a child born with a rare congenital disorder and a brother with a chronic disease became the springboard for Dr. Harsha Rajasimha to apply his years of postdoctoral training at the NIH and FDA to accelerate therapies for rare and common conditions. Patient travel requirements and the pandemic forced the demand for decentralizing clinical trials and embracing digital technologies needed to accelerate the process of bringing new medicines or vaccines to patients who need them over three times faster. Jeeva set out to focus on mitigating risks to emerging biopharma clinical trial sponsors as true technology partners, seeking time and cost-efficient ways to execute early-stage clinical trials with minimal risk without compromise. Their reduction of the logistical burdens on patients and study teams by over 70% has resulted in their eClinical platform being selected by a joint venture of Georgetown University Medical Center and Frantz Medical Group for a major cancer trial. The Virginia-based company's modular software-as-a-service platform is fully scalable and facilitates patient enrollment, engagement, and evidence generation in clinical trials on any browser-enabled mobile device. Visit https://jeevatrials.com/.
Dr. Padma Rammoorthy has a career spanning over 26 years. She has transitioned from clinical practice to health education and lifestyle medicine in her career. Having made significant contributions to raising awareness about maternal health in India and worldwide through her successful social start-up, she has been honored with prestigious awards such as the India Innovation Growth Program and the World Summit Award.
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