Introduction

The process of drug development is lengthy and expensive. Phase III randomized controlled clinical trials (RCTs) are essential for ensuring efficacious drugs that adhere to high safety standards but can take 3 to 7 years to complete and account for approximately 60% of the overall trial costs. A third end without drug approval. It has been estimated that nearly 86% of all trials (not only Phase III) do not meet enrollment goals and 32% of Phase III trials fail due to poor recruitment. This may be due to poor recruitment and enrollment mechanisms that fail to bring the best-suited patients to a trial in time. 

This blog delves into the critical steps in patient recruitment, and enrollment, highlights challenges in each step and explores how leveraging new technologies and methodologies can improve clinical trial efficiency, decrease costs, and expedite drug approvals.

Roadblocks to Clinical Trials Recruitment and Enrollment

Recruitment

Patient recruitment involves identifying and attracting potential participants for a clinical trial. It includes various activities aimed at informing and encouraging individuals to consider participating in the study to create a sufficiently large pool of candidates who meet the initial eligibility criteria for the trial. Effective prospective selection of a subset of the population in which the drug's effect can more readily be demonstrated is key to increasing the likelihood of observing the drug's efficacy and is known as clinical enrichment. 

One stumbling block with clinical trials is that participants are often not representative of the broader population, which is necessary to ensure that trial results are generalizable​. Underrepresented populations in clinical trials include racial and ethnic minorities, women, older adults, individuals from lower socioeconomic backgrounds, and those living in rural or underserved areas. These groups often need help overcoming barriers to participation in clinical trials such as the financial costs and logistical challenges to participate (e.g. finding the time to participate at a clinical trial site which may be far away), lack of awareness, and mistrust in the healthcare system. Addressing these issues requires interventions such as targeted outreach, flexible study designs, and improved communication. 

An example of where it is crucial to have a clinical trial cohort that is representative of a diverse population is the phenomenon of population‐specific variable drug reactions in response to the same treatment. To observe such effects, clinical trials require a large, diverse population to detect population-specific adverse events or variability in efficacy. Otherwise, if a drug is not observed to produce serious adverse effects in the population in which it was evaluated, but turns out to produce serious adverse effects in groups in which it was not evaluated, this could lead to serious morbidity and mortality when prescribed to vulnerable groups. Efforts are currently underway to improve clinical trial diversity but there continue to be disparities in clinical trial cohort representation. For example, the same ethnic or minority groups, who were disproportionately affected by COVID-19 in the United States, remained underrepresented in COVID-19 clinical trial recruitment and enrollment. 

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Enrollment

Once an individual has met the specific eligibility criteria for a clinical trial, they can be formally enrolled as participants who have provided their consent to participate, thereby allowing the study to proceed with data collection and analysis. This stage includes:

• Screening: Assessing potential participants through various methods such as medical history reviews, physical examinations, and laboratory tests to ensure they meet the detailed inclusion and exclusion criteria of the study.

• Informed Consent: Providing potential participants with detailed information about the study, including its purpose, procedures, risks, benefits, and their rights as participants. This is followed by obtaining their written consent to participate in the trial.

• Randomization: In studies that require random assignment, participants who pass screening and consent to participate are randomly assigned to different study groups (e.g., treatment group vs. control group).

Similar to recruitment, there are several well-known hurdles to enhancing diversity in clinical trial enrollment relating to geography, lack of resources to support participation (e.g. logistics of taking time off of work to travel to participate in a long-term manner), support from physicians, and more.

Innovations to Improve Recruitment and Enrollment

Common routes for participation involve referrals from healthcare providers, information sessions from community groups, advertisements and selection via electronic health records (EHRs), and registries. One route that can be optimized to improve recruitment is the use of patient registries. They provide comprehensive patient data of willing potential participants that can be leveraged to improve representation in clinical trials and streamline various critical steps including patient recruitment, monitoring, and follow-up, thereby reducing time and expenses. 

Another is the use of machine learning (ML) to find correlations in large datasets and natural language processing (NLP) to understand and correlate content in written or spoken language, such as unstructured data in physician’s notes. Clinical trial recruitment management systems/software linked to EHR data can also identify eligible patients based on characteristics derived from the EHR to improve and optimize patient–trial matching and recruitment.

Digital technologies, particularly those that could help patients enrol and participate remotely, could be very useful in improving enrollment and supporting participant retention. When evaluating the use of remote technology in clinical trials, a study reported that 60–85% of respondents would be more inclined to participate in a trial if they were able to use remote technology. For example, informed e-consent tools, including electronic forms or even teleconferencing, can be used to obtain consent without a patient’s physical presence.