Clinical Trial Recruitment: Can a Comparative Analysis of Database-Driven, Digital Technology, and Integrated Strategies Break the Cycle?

Patient recruitment and retention are among the most critical challenges in the fast-evolving world of clinical trials. In 2000, we had 2,100 clinical trials. As of 2024, we have over 477,000 clinical trials. This is an increase of over 22,000 percent, yet patient enrollment and retention rates have not changed much. This data alone lets us know we don’t have a shortage of clinical trials, and we also don’t have a shortage of patients, with there being 8 billion people in the world.

In an industry so slow to change, I believe it ultimately lies within its approach to enrolling patients in clinical trials over the years. According to a research paper that was published in 2023 titled, “Strategies for participant retention in long term clinical trials: A participant –centric approaches,” the success of a clinical trial often hinges on the ability to not only recruit participants but to retain them throughout the study’s duration. Three primary approaches dominate the recruitment landscape: database-driven strategies, digital technology-driven approaches, and integrated (a combination of the two). While all methods have their merits, one notable difference lies in retention rates—a critical metric that can significantly impact the overall success of a trial.

The Role of Retention in Clinical Trials

Retention in clinical trials is the study’s ability to keep participants engaged from enrollment to completion. High retention rates are crucial because participant dropouts can lead to incomplete data, prolonged study durations, increased costs, and even the failure of the trial to meet its objectives.

Another new and essential retention aspect with the three approaches is the Food and Drug Omnibus Reform Act (FDORA), signed into law in December 2023. With this legislation came Diversity Action Plans (DAPs). This stated that ALL Phase III and pivotal trials must provide a DAP with the protocol in submission to the FDA for trial approval. The DAP must contain accurate goals for demographics regarding race, ethnicity, age, and gender. That same demographic data must be reported monthly to the FDA to ensure the initial goals the sponsor / CRO submitted to the FDA are tracking in accuracy. It also stated that consensus data (heat mapping) can only be used for ubiquitous drugs (Vaccines) and must not be used for therapeutics that target a specific disease state. This dramatically limits the resources from which the data comes. It also stated that if the monthly reported demographics deviate from the FDA-approved DAP goals, the FDA reserves the right to halt the trial for 90 days. This allows the sponsor to come back into alignment with the original goals outlined in the original DAP approval. Most are under the impression that the DAP is simply guidance. This is incorrect, as the verbiage implied during the open comment period is guidance. Under this legislation, we can fully appreciate the dramatic impacts on retention should the recruitment for the trial result in a deviation from the initial goals the sponsor / CRO submitted. We all know you cannot have a trial without patients, and recruiting the patients will require more thoughtfulness. Sponsors now cannot afford to pick a CRO, site network, or patient recruitment vendor that cannot give accurate demographic goals. This legislation minimizes the traditional ad-agency approach for patient recruitment and requires a major emphasis on a database-supported model.

Database-Driven Recruitment: A Proven Approach

According to professionally researched public data, only two companies have a database containing tens of millions of patients, respectively, which matters immensely. One of those companies was acquired by a large CRO in 2018, and the other company is privately held and still offering its patient recruitment services. A database-driven approach utilizes millions of patients looking for a clinical trial. This approach for patient recruitment in clinical trials generally enjoys higher retention rates. These databases often consist of individuals who have previously expressed interest in participating in clinical trials, have already been educated about clinical trials, have had their identification verified, have a confirmed diagnosis, in most cases, and sometimes have their medical records already in hand. Although many patient recruitment vendors boast of their database, industry resources assess the next closest company only has a patient population between 1.6M-2.8M people in comparison to the two mentioned above.

Retention Rate

The effectiveness of such database-driven recruitment strategies in achieving hire retention rates is supported by several studies and industry reports ranging from 70% to 90%. Although, the exact retention percentage can vary depending on the specific tools and methodologies used (MedDeviceOnline, JAMA, Springer Link, BioMed Central). This higher retention can be attributed to several factors:

• Pre-existing Interest and Commitment: Patients in a database have often actively sought out clinical trial opportunities or have been pre-screened, indicating a higher level of commitment.
  
• Established Communication Channels: Companies with large databases often have established communication protocols, including regular follow-ups and personalized engagement strategies, which help maintain participants’ interest and involvement throughout the trial.
  
• Trust and Relationship Building: Participants recruited through a database may have had prior interactions with the recruitment company or the clinical trial sponsor, fostering a sense of trust that can contribute to higher retention. This can lead to a database of patients qualified/seeking a clinical trial.
  
• Time and Cost: The database-driven approach takes tremendous time and effort and is costly. This reflects a commitment to the patient where the patient finds meaningfulness in the time it took to establish the relationship. This might be why only one patient recruitment company with this capability is left in the market.

Digital Technology-Driven Recruitment

On the other hand, digital technology-driven recruitment leverages the power of online platforms, social media, targeted digital advertising, website design/deployment, and site analytic software to attract and manage a diverse and broad pool of potential participants. While this approach offers the advantage of scalability and reach, retention rates tend to be lower compared to database-driven methods. This is mainly because it is an ad-agency approach utilizing technology and social media. In cases where advanced site analytic software was deployed, it has been documented that the sites value the ability to assess their deficiencies, adjust according to the data, review where the patient is in the process, and have a better feel for the patient experience. Still, overall, they feel it can create additional burdens as well.

This is still an especially important aspect of patient recruitment, as it allows reach and decentralization to help meet the patients where they live. It also helps facilitate the DAP plan goals, less than the database-driven recruitment. Still, it does help more people, increasing diversity in communities that may have never had a chance to participate in a clinical trial.

Retention Rate

Retention rates for digital technology-driven recruitment range from 50% to 70%. Much lower than database-driven recruitment. Specifically, these retention rate percentages are reflected in articles and discussions on the impact of digital tools and technology in clinical trials (mdgroup, JAMA, Springer Link). Several factors contribute to this lower retention:

• Broader and Less Committed Pool: Digital recruitment often attracts participants who may have a casual or fleeting interest in clinical trials. These individuals might click on an ad out of curiosity rather than a genuine commitment to participate, leading to higher dropout rates.
• Varied Levels of Awareness: Participants recruited through digital means may not be as informed about the trial process, expectations, or the significance of their involvement, resulting in lower levels of engagement and retention.
• Need for Strong Engagement Tools: Digital platforms must work harder to keep participants engaged. While digital tools like apps, email reminders, and online portals can enhance engagement, the initial bond with participants is often weaker than in database-driven approaches, making retention more challenging.
• Lack of Accuracy in DAP Plans: Digital platforms do not have a database and usually rely on consensus data. We have already discussed the use of consensus data regarding FDORA legislation. Due to the main source of patient recruitment coming from the above, digital platforms often lack accurate contact information. This can lead to high billing in referrals to the sponsor with mediocre quality in randomization. The advantage of a database-driven patient recruitment approach is that it allows for a trial simulation. This is one of the most accurate ways to satisfy the DAP goals listed in the new legislation. Again, according to the T-test, tens of millions of patients are required in a database to satisfy the population’s representation.

Bridging the Gap: Strategies for Improving Retention in Digital Recruitment

Despite the challenges, digital recruitment is not without its strengths, and there are ways to improve retention in this approach:

• Enhanced Screening: Implementing more rigorous screening processes during the initial recruitment phase can help ensure that participants are genuinely interested and committed to the trial.
• Improved Education and Communication: Providing comprehensive information about the trial, its purpose, and the importance of each participant’s role can help increase engagement and retention.
• Leveraging Digital Tools for Continuous Engagement: Utilizing apps, personalized emails, and regular check-ins can help maintain participant interest and commitment throughout the trial.
• Integration of Both Digital Technology-Driven Recruitment and Database-Driven Recruitment

Combining technology-driven and database-driven patient recruitment in clinical trials can significantly enhance patient retention, potentially achieving rates as high as 95% -100% (Springer Link, Applied Clinical Trials, Digital Patient Recruitment). This is research changing, yet the industry has been slow to adopt. This requires a patient recruitment company to have a robust database of people seeking a clinical trial and a digital technology-driven platform.

The more robust the technology offerings, the more complimentary they are to the database-driven platforms and the tens of millions of patients you have in the database, and vice versa. It is often said that we do not have a patient shortage problem for clinical trials but a patient enrollment problem. I would agree, but there is a caveat to the fact that we also have an understanding and trust problem. This may be the main issue altogether. We have been sitting on the same patient enrollment rates and dropout rates for years. Integration of both approaches should be the ultimate goal of any sponsor. The unfortunate reality for sponsors is that their options in the integration-driven recruitment of these approaches are limited by only a few vendors with these capabilities.

Conclusion: Choosing the Right Approach

When it comes to patient retainment for clinical trials, the choice between a database-driven (70% – 90% retention rate), a digital technology-driven (50% – 70% retention rate), or an integrated approach (95% – 100% retention rate), should be determined by the specific needs and goals of the study. While database-driven recruitment offers the advantage of higher retention rates, digital technology-driven strategies provide unparalleled reach and scalability. Combining both is where “cures” are transcended beyond a hypothesis and into reality.

For sponsors, understanding these retention differences is key to designing an effective recruitment strategy that attracts participants and keeps them engaged until the trial’s conclusion. By balancing the strengths of all approaches, sponsors can optimize their recruitment efforts, ensuring the success of their clinical trials in an increasingly competitive landscape.