Clinical Trial Basics: Pre-Screening and Screening

What is screening in a clinical trial?

Clinical trial regulators define screening as the process of checking a potential trial candidate against the trial’s eligibility criteria to determine if he/she qualifies for the clinical trial.

Screening can begin before enrollment, but any invasive screening procedures must wait until after the participant has given their informed consent.[1] The information gathered about both eligible and ineligible candidates is usually recorded in a screening log, which stakeholders can use to gain various insights such as identifying selection bias that arises during clinical trial recruitment.[2]

Clinical trial screening is crucial because it maintains the integrity of the study by ensuring all the participants meet specific criteria, known as the eligibility criteria. This selectivity is designed to minimize extreme variations in the study population that have the potential to skew findings, or which could expose people to treatments that are inappropriate for them. Further, screening to establish an appropriate trial population provides a scientifically robust context for determining the outcomes of the study treatment, and improves the accuracy of the findings.

Screening tends to be particularly strict for phase 1 clinical trials (and perhaps phase 2 trials as well). The primary purpose of these early-phase trials is to determine the safety, tolerability, and potential adverse reactions of the study drug. This typically (but not always) requires administering increasing doses of the study drug to healthy volunteers. As the study drug progresses to later phase III trials, more information has been gathered about the safety and tolerability of the treatment - the eligibility criteria can then sometimes be relaxed as investigators can be more certain that the drug is safe at the established dose. Further, this can help broaden the pool of eligible participants as more participants are needed in phase III trials to collect sufficient data to make conclusions about the drug’s efficacy, and it also increases the generalizability of the study results.

Eligibility criteria

In a clinical trial, the eligibility criteria are a set of defined demographic characteristics, physical conditions, health statuses, and/or medical histories that are used to define which candidates are fit (eligible) for participation in the trial. Eligibility criteria usually consist of both inclusion criteria and exclusion criteria:

A candidate who meets all of the inclusion criteria and none of the exclusion criteria qualifies to enroll in the clinical trial. A candidate who either does not meet the required number of inclusion criteria (as established by the sponsor, which may be all or a specific minimum), or who meets one or more exclusion criteria, does not qualify. If a participant is found to be ineligible during screening, or decides not to participate at some point during the screening process, the situation is considered a screen failure.

Designing the eligibility criteria

The specificity of the eligibility criteria will depend on the clinical trial and its research goals. It is important to recognize that the more in-depth the eligibility criteria are, the more time and resources may be required to screen each candidate. Each eligibility criterion should be thoroughly assessed and should aim to define the study population appropriately, ensure participant safety, and also make the trial accessible to a patient pool that is as diverse as possible and representative of the general population. Recruitment represents a major bottleneck in clinical trials, so avoiding unnecessarily restrictive eligibility criteria should be a priority.[3]

The study sponsor determines the inclusion and exclusion criteria with careful consideration as part of the trial design. This involves finding a balance between details that are essential and those that are trivial, and between being scientifically ideal and representing the real-world (scientific robustness vs. generalizability of results). If eligibility criteria are too strict, it will be difficult to reach enrollment targets and the study sample may not represent the broader population with the condition being studied. On the other hand, if the eligibility criteria are too lax, there could be too many confounding factors amongst the study sample to draw scientifically valid conclusions. Eligibility criteria are also meant to ensure that the study drug is not given to participants who are at higher risk of harm, or for whom participation in the study would be unethical due to an urgent need for receiving an established standard treatment.

Clinical trial pre-screening vs. screening definition

Pre-screening is a precursor to screening; a preliminary assessment of eligibility based on basic information about the candidate. Pre-screening usually does not need to be done in person, and can instead be completed remotely (i.e., over the phone or via video call or online survey). Prescreening cannot include any invasive procedures, tests, or interventions - those will be done in the later screening process.

Clinical trial screening occurs after a patient has consented, and usually involves collecting more detailed health information and possibly performing laboratory tests to determine patients’ eligibility at a more specific level. It is a more comprehensive evaluation that complements the pre-screening, and is only possible after informed consent due to data privacy and ethical regulations. Screening is often done on-site at a pre-trial screening visit, in the presence of a healthcare provider, and may involve assessments such as blood work or measurements of physiological metrics.

Advantages of pre screening patients

Pre-screening is a very effective technique for quickly sifting through many candidates to narrow down the potential participant pool. In the pre-screening stage, candidates have yet to give their informed consent, so questions are limited and only certain inclusion and exclusion criteria can be assessed. Of course, researchers still need access to databases of patients to pre-screen, and they also need a way to compile a list of pre-screened candidates and then contact them to continue the enrollment process. That is where Power comes in. When patients search for clinical trials on our user-friendly platform, they are offered to answer a few basic questions - which are established by the study sponsor - to help them determine their basic eligibility themselves. Besides empowering patients to make informed decisions, this reduces the number of screen failures later on and leads to the creation of a database of high-intent participants the sponsor can use to contact the prospects and proceed with the enrollment process.

What criteria can be assessed through pre-screening?

Pre-screening is limited to demographic factors and basic medical history that can be gained without any tests or intervention, and commonly includes parameters such as:

• Age
• Sex
• Height
• Weight
• Location
• Confirmation of condition and severity, or certain details about the condition or its subtype (i.e., specific scores on qualitative tests of disease severity)
• Symptoms and related timeframes (i.e., “have experienced ringing in your ears for more than 3 months but less than 2 years”)
• Prior treatments and health decisions (i.e., “did not respond to prior treatment with SSRIs”)
• Logistical factors (i.e., ability to read or to access the study site)
• Willingness to be exposed to the study drug/device

Pre-screening is a valuable tool for finding high-eligibility candidates and thereby reducing screen failures later in the enrollment process, which can be costly to sponsors and trial sites.

Informed consent

According to the FDA definition, a candidate gives informed consent when they confirm that they are aware of the details of the trial and willingly agree to go through the screening process and to participate in the research study, without influence or coercion.[4] This is formalized through an informed consent form (ICF).

Informed consent is a central component of ethical conduct in clinical studies, which safeguards a candidate’s autonomy by confirming their ability to make a voluntary decision when given complete information about the trial. Giving informed consent means the potential participant:

• Understood all aspects of the trial, from the way it will be conducted to its potential risks and what is expected of them
• Was able to ask questions and receive answers
• Was given adequate time to discuss the clinical study with their family, friends, and/or doctors

What happens at a screening visit?

Once a prospective participant has given informed consent, they can continue onward to the full screening process. During a screening visit, potential participants generally visit the trial site in person, where they will interact with and be evaluated by a member of the trial staff, such as the principal investigator or a study nurse or physician.

The screening process is highly trial-specific, but candidates will normally go through a series of evaluations, that could include, amongst others:

• Undergoing a physical examination (blood pressure, heart rate, etc.)
• Undergoing diagnostic tests such as CT scans, X-rays, or MRIs
• Providing samples for lab testing such as urine, stool, or blood samples
• Providing and discussing their in-depth medical history
• Completing surveys that may assess mental health status, pain levels, or other specific health conditions or outcomes

Trial staff will then compare the results from these assessments against the trial's eligibility criteria to determine whether or not the candidate qualifies for enrollment. If the candidate qualifies, he/she can then make a decision whether or not to consent to participate, and thus formally enroll in the trial. This would usually take place after the screening visit, although in some cases it may be possible in the same visit.

How clinical trial screening design can be optimized for improved patient recruitment

Clinical trial screening is an important part of patient recruitment and enrollment. The cost of screening patients can get out of hand if the clinical trial screening protocol is not optimized, as high screen failure rates and filtering out large numbers of ineligible candidates can cost sponsors significant amounts of money as well as time.[5] Investing time in designing a clinical trial screening process that incorporates digital tools and patient-centric communication is worthwhile, as it has the potential to decrease screen failures as well as make trial information more accessible and understandable for participants. Establishing appropriate eligibility criteria is the first step, as these will dictate the entire screening process and how it may be carried out.

Solution 1: Use digital pre-screening tools and technological solutions

Using digital tools for pre-screening can drastically increase the size of the sample population by connecting researchers with patients, and also allows patients and researchers to evaluate basic eligibility early on, reducing screen failures and freeing up resources for final screening..

Further, digital pre-screening tools provide functionalities such as improved access to screening logs by keeping them in a centralized and secured location, and also allow various stakeholders to access consistent information regarding recruitment efforts in order to guide future decisions about recruitment, such as improving recruitment marketing strategies and screening processes.

Power is a prime example of a digital tool designed for streamlining pre-screening, which also addresses the issue of patient accessibility. It opens up access to trials for potential participants by providing clinical trial information in easy-to-understand language, empowering them to decipher eligibility criteria and verify their basic eligibility themselves in a few clicks. Simultaneously, it represents an excellent tool for researchers and sponsors to publicize their clinical trials and define custom pre-screening questions, helping match eligible patients with the trial.

Solution 2: Use clear, concise, and engaging ads and informed consent forms

How clinical trial teams communicate with their patient populations can also significantly influence and define the group of people who respond. Information about the trial can be transmitted to patients in multiple ways, including:

• Digital recruitment advertisements and outreach campaigns launched across social media platforms such as Facebook, on search engines, etc.
• Physical recruitment ads such as posters, newspaper ads, recruitment flyers, etc.
• Promotional and educational materials, which can be handed out in patient advocacy organizations, local healthcare centers, etc. or distributed online via email campaigns, etc.
• Informed consent forms; these should be the definitive source of information for the patient, and can also be completed electronically via eConsent

The outreach and recruitment process can be made much more effective by empowering patients to engage in their healthcare decisions and make informed decisions by ensuring that all study materials provide information in a clear, concise, and transparent manner. The concept of patient-centricity is becoming increasingly popular and important in clinical research, which prioritizes the explicit consideration and optimization of patients’ first-hand experiences in trial design and communications. Patient-centric communication involves the use of clear, concise language focused on maximizing transparency and understandability. Being transparent and clear allows patients to understand the eligibility criteria themselves, which serves as a type of automatic pre-screening by reducing interest from clearly ineligible candidates who may have been confused by the study material they first saw.

Solutions such as eConsent can further facilitate screening and enrollment, as it supports a way to provide candidates with interactive content that can more thoroughly and fully explain the study, helping ensure the patient understands their eligibility and what is expected of them, without tying up on-site resources.

Conclusion

Clinical trial screening is an extensive undertaking with significant influence on overall recruitment success in clinical trials. Thoughtful design of the screening process and eligibility criteria, including the use of digital pre-screening solutions and patient-centric communication, can optimize recruitment efforts and minimize losses and delays.