How do I recruit my test subjects for the evaluation study?

In theory

For an evaluation study to have meaningful results, it is important to calculate how many patients need to be included in the study in advance. The study is "underpowered" without a suitable sample size, and there is an increased risk that the positive healthcare effect of the investigated DiGA will not be found, even if it exists.

In the case of DiGA evaluation studies, the implementation period is also limited. The study must be completed after twelve months. If it is not possible to enroll the required sample size in the planned recruitment period (e.g. due to a poor strategy) the study duration would have to be extended until all patients have been recruited. Although there is an option to justifiably extend the study, approval is not guaranteed after an individual assessment and, if granted, will only take place gradually. A study extension is not a practical option during the recruitment phase at the start of the study. Adjusting the duration also requires adjusting the entire study schedule and, in many cases, leads to additional costs.

The Federal Institute for Drugs and Medical Devices (BfArM) requires a transparent presentation of the selected recruitment method(s) for the planning of the evaluation study. This should include information on the location and type of recruitment. In any case, it is necessary to explain whether the recruitment is monocentric, i.e. carried out at one clinical center (e.g. a hospital department or practice), or multicentric, i.e. carried out at several clinical centers. This is because the choice of recruitment method(s) has direct consequences for the composition of the study population. Online recruitment (e.g. via a study website or social media) is also becoming increasingly important.

In practice

The majority of DiGA manufacturers opted for multicenter recruitment (n=25) exclusively. 11 manufacturers conducted monocentric recruitment and 2 manufacturers recruited exclusively online. Four DiGA studies used multicenter recruitment in combination with online recruitment, and 13 studies used monocenter recruitment in combination with online recruitment.

Our experience

The recruitment potential of patients who meet the inclusion criteria is often greatly overestimated before the start of the study, which only becomes apparent when conducting the study and leads to the delayed inclusion of patients. This phenomenon is known as Lasagna's Law. Therefore, during study preparation, the planned recruitment strategy should be carefully checked to ensure (1) a realistic chance of including enough patients in the study within the (2) allotted time.

An unrepresentative selection of study participants, known as selection bias, is one of the most important sources of confounding. Errors in recruitment can have consequences for the transferability of the study results to the future user population. In the worst-case scenario, the results from the evaluation study cannot be observed later in the standard of care of DiGA users.

Patients can be recruited to participate in a DiGA evaluation study in different ways— e.g. via medical practices, clinics, online and print media and patient organizations. The way in which patients enter a study can have an influence on the composition of the study population (e.g. because younger people tend to use more online channels and older people use more print media). Similarly, monocentric recruitment via a single study center can lead to the inclusion of only a specific patient group. It is therefore generally advisable to conduct multi-center studies with several study centers. In addition to generalizability, this also increases the speed of recruitment.

In traditional offline recruitment strategies, the location of study centers can affect the diversity of participants, as patients can only be recruited within a limited radius. Studies, especially those with digital products, can be conducted in a decentralized manner. These so-called Decentralized Clinical Trials (DCT) are studies that are conducted remotely rather than in an on-site trial center or practice. This means that, for the most part, the subjects can stay at home throughout the study. Decentralized studies are advantageous because a large sample size can be recruited in a shorter period, independent of regional study centers. Disadvantages of this approach include identifying suitable patients and ensuring compliance with ethical principles. For example, the responsibility for the protection of study subjects always lies with a doctor or other healthcare professional— under no circumstances is it in the hands of the study subjects themselves.

When using information and advertising materials to recruit patients, it is necessary to have these approved in advance by the responsible ethics committee. This procedure serves to protect patients and investigators from ethically unacceptable or legally inadmissible actions, such as false promises of participation benefits.

The development of an effective recruitment strategy is an essential part of study planning.? As a scientific institute, we can offer the entire research process in close cooperation with the Clinical Research Organization (CRO) GREENBAY research GmbH in a seamlessly planned and continuously coordinated workflow—from study planning and execution, data analysis and reporting, to the publication of the results in a manner appropriate to the subject and target group. DiGA evaluation studies can be conducted by us as center-based or decentralized clinical studies. Our DiGA expert Tonio Sch?nfelder will be happy to answer any questions you may have.

The WIG2 Institute’s DiGA-FAQ addresses the questions that have been frequently asked in our previous collaboration with DiGA manufacturers.

DiGA-FAQ // Evaluation study // Question 3: How do I recruit my test subjects for the evaluation study?

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