Patient screening, a vital step in the clinical trial recruitment process, is when interested participants are assessed for their eligibility for a given trial using select inclusion/exclusion criteria. These criteria help characterize the target patient profile to ensure patient safety, better efficacy, and optimized signal detection.
Traditionally, patient screening was done in person at a clinical trial site.
Today, patient screening can be done both electronically and remotely using computers, cell phones, tablets, etc. This has improved the process, bringing optimization, efficiency, and convenience to what once required an in-person visit.
Effects of screen failures
The fundamental purpose of patient screening is to enable the successful enrollment of the target patient: in other words, ensuring the patient is qualified as a “good fit” for the study. Getting this process right while minimizing screen failure rates is a key industry challenge that is fundamental to efficient, effective, and successful enrollment. According to a commonly cited statistic from the Tufts Center for the Study of Drug Development (Tufts CSDD), some 11% of active sites will fail to enroll a single patient.
Screen failure rates are highest in interventional studies (Phase 2, 3, and pharmacokinetic) and impact enrollment across multiple therapy areas, from Alzheimer’s disease where screen failure rates range from 15 to 35 percent, to genitourinary cancer trials where we see rates in the order of 20 and 30 percent.
The consequences of high screen failure rates are enrollment delays, increased cost due to longer delivery timelines, delays to endpoint generation, and in some cases termination of the study. As observed by Tufts CSDD executive director Ken Getz, a typical clinical trial is often forced to double the planned enrollment period just to reach recruitment targets. Furthermore, according to Getz roughly 1 in 10 sites will still fail to enroll any patients, even after such an enrollment window is extended. High screen failure rates can cost sponsors anywhere from $600,000 to $8 million every day the study is delayed, and study termination can hamper the pipeline of beneficial new treatments.
Key causes of screen failure
When we consider the key factors behind screen failures, it’s clear that a well-designed, patient-centric screening strategy can significantly reduce screen failure rates. Two key contributing factors leading to screen failures are overly stringent inclusion/exclusion criteria and patient refusal due to concerns about potential risks and the logistical burden of participation.
A 2016 study found 69% of screen failures occurred as a result of inclusion/exclusion criteria, and 16% of screen failures occurred when patients refused consent for reasons such as:
- Perceived severity of risk
- Concerns over the consent document, such as a lack of time to understand it or feeling overwhelmed by the information it contained
- Concerns over potential future expenses or the perceived burden of participation related to the number of required procedures (e.g. multiple blood draws)
These findings were supported by an eight-year study with the National Institute of Mental Health which found two-thirds of all patient refusals occurred because patients felt trial participation would be more burdensome than beneficial. In that study, 36% of patient refusals were due to protocol concerns, and 33% were concerned about potential inconvenience study participation might create.
When considering the factors driving the majority of screen failures, it’s clear to see how issues of patient confusion and inconvenience are well within the control of the trial organizers.
A patient-centered clinical trial design can help to ensure studies are developed around the patient. This includes taking established care plans and treatment regimes into account, as well as the critical relationship a patient has with their healthcare providers.
Patient-facing material, including consent documents, need to ensure patients are well informed. By careful use of patient-friendly language that avoids overly technical information and makes use of multimedia methods to communicate relevant information in alternative ways, sponsors can aid comprehension, improve patient engagement, and avoid undue patient burden.
Additionally, while some complexity to protocols and criteria is certainly warranted, a closer look can help ensure protocols are meaningful and inclusion/exclusion criteria are chosen deliberately, avoiding unnecessarily limiting criteria.
Getting the design right
A successful clinical trial doesn’t start with patient screening, or even at recruitment. It begins with the trial design. Intelligent trial design begins with the careful characterization of the target patient and the efficacy and safety measurements critical to success, while also considering the patient's perspective.
It’s crucial to consider what type of patient the trial is looking for and whether, based on the inclusion/exclusion criteria, that target patient group is realistic—are such patients actually out there? For example, prerequisites for existing therapies (dosing, stability optimization, or line of treatment) are key to evaluating feasibility for enrollment and minimizing the potential for high screen failure.
Of course, there are times to be stringent to avoid unnecessary risk. But tightly defined criteria that are not practically meaningful can create a high number of avoidable screen failures. A more effective approach is to be pragmatic and realistic, taking the time to understand the patient and where they sit in the treatment pathway. It is critical that the study population is representative of the patient population for whom the treatment is intended (assuming market authorization is successful).
Identifying 3-4 critical characteristics that can help sites to profile the “right” patient will enable a more effective and efficient screening process. Keeping to discrete and targeted study measurements that are meaningful to both the research and the patient also fosters more convenience to participation and stronger patient engagement.
Using digital tools to optimize success
Prior to digital capabilities, trials were fully dependent on a brick-and-mortar site, the site’s database of patients, and the proximity (or lack thereof) of those patients to that site. In addition to complicating initial screening, this also contributed to reduced participation over the course of the trial due to fatigue in attending rigid in-person clinic schedules.
The current digital enablement helps study teams optimize screening strategies and reduce the on-site screening burden for investigators by minimizing screen failure rates through the use of digital pre-qualification tools. Such strategies can help broaden the geographical reach of a study, provide access to previously underrepresented populations, and facilitate their participation in clinical trials so that sponsors can ensure the applicability of research findings to a more representative and diverse patient population.
Digital screening tools also have the ability to capture, standardize, and integrate vast amounts of patient-specific information from multiple sources, including clinical records, genomic testing, and centralized screening and prognostic tools, all of which help enrich the study population to improve safety and signal detection, as well as drive the need for fewer patients.
Whilst recent technological advances offer ways in which teams can bolster screening success, these tools must meet patients where they are. This means that the study process needs to fit into the patient’s lifestyle while reducing the need to travel and take time away from home, school, or work.
By leveraging digital technologies, study teams can ease patient burden using intuitive and familiar technology. Gathering data from the comfort of a patient’s home, for example, or using remote capabilities for patients who live a considerable distance from the site, or designing a study aligned to the patient’s current treatment journey—in terms of the regularity of the visit schedule, for instance—all of these are effective ways to design the trial around and specifically for the patient.
Electronic consent tools go even further in streamlining and simplifying the consent process to minimize patient refusals. With electronic consent, teams can present a wealth of information in a richly engaging multimedia platform. At the same time, electronic consent empowers patients to proceed at their own pace and provides opportunities to ask questions or seek clarification at any point through the consenting process.
With all the possibilities afforded by accelerated digital health technologies comes a slew of new considerations: marrying a treatment schedule, visit schedule, and assessment schedule in a way that’s convenient for the patient; thoughtfully leveraging remote capabilities to gather data from a patient’s home; and ensuring both clinician and patient still feel engaged and cared for when tasks and assessments are transitioned to a more virtual setting.
Recognize the larger implications of the screening process
Through the use of digital eScreening solutions, sponsors can now broaden the reach and accessibility of trials through a leaner trial footprint and recruit an enriched trial population—meaning fewer sites, fewer patients, fewer screen failures, and an acceleration of drug development cycle times.
The wider net allowed by going digital with decentralized trials and democratized study participation promotes inclusive enrollment across geographic, racial, gender, age, income, and socioeconomic groups. This is crucial to ensuring the drug or device is tested in those individuals for whom the treatment is intended post-registration.
Of course, recruiting sufficient eligible patients requires taking steps to minimize screen failures, which account for a substantial segment of study startup delays. Globally, 80% of trials do not enroll on time, and each screen failure costs the study sponsor an average of $1,200.
When recruiting through digital media, it’s important to be aware of bias-based factors such as limited access to or fluency with digital technologies. Otherwise, the individuals who are most appropriate for a certain trial, or who might most benefit from the trial’s research, may be unintentionally excluded.
Accelerating research through a patient-first approach drives inclusivity in the research space, enabling more communities, and thus more people, to have access to the right health care.
The future of patient screening is now
Successful trials begin with successful patient screening. Failure to meet enrollment targets can lead to cost overruns, delayed endpoint capture, extended timelines, missed milestones, or even study termination.
Implementing flexible, scalable, and compliant tools enables teams to recruit patients no matter where they are — at the site or remotely. Electronic consent tools like Medable’s Total Consent enhance patients’ comprehension and help them feel more engaged with study goals and procedures, thereby increasing the likelihood they will grant consent and enroll.
And, resources like Medable’s Patient Advisory Council provide ongoing insights regarding patient access, outcomes, and the practicality of the patient experience.
To meet your enrollment targets faster, drive inclusivity and diversity, enhance patient engagement and retention, and facilitate successful trial completion, consider integrating digital screening and consent tools into your study.