What aspects does a clinical investigation need to demonstrate the positive healthcare effect of a DiGA?

Since 2022, the National Association of Statutory Health Insurance Funds has criticised the high prices paid for DiGA and the low level of evidence that they believe is sufficient for reimbursement. In particular, they are calling for a new balance between the price to be reimbursed and the economic benefit.

We believe it makes sense to ensure a high-quality DiGA study for an elaborate and complex project such as a clinical investigation only with excellent and very thorough preparation together with scientists, clinicians, specialised independent research institutes and with a team within the company that understands the challenges very well.

A distinction must be made in clinical studies between the requirements for proof of positive healthcare effect for planned provisional and final inclusion in the BfArM's DiGA Directory.

Provisional inclusion

For provisional inclusion in the DiGA Directory, the manufacturer must submit a plausible justification showing that the DiGA could have a positive healthcare effect. This must be scientifically substantiated together with the test plan for the planned clinical trial in the evaluation concept. Provisional inclusion makes it possible to collect the necessary data within a trial phase of up to 12 months (extendable by a further 12 months).

Requirements (not comprehensive):

1. general and plausible justification:

• Systematic data evaluation showing that DiGA potentially has a positive healthcare effect.
• Initial observational studies, collection of data from users or smaller study populations can serve as a basis.
• The target population must be defined using the ICD-10 code (standardised official classification for coding diagnoses). Aggregation of several ICD-10 codes must be justified according to scientific and clinical standards.
• The positive healthcare effect must be consistent with the intended purpose, functions and content of the DiGA as well as the published statements (e.g. in promotional material)
• In the case of "diagnostic DiGAs", it must be proven that earlier diagnosis leads to a better medical outcome. This often requires extensive studies to prove the diagnostic quality.

2. evaluation concept:

• An evaluation concept prepared according to internationally recognised scientific standards with the following contents:
• Presentation of the background on the basis of a literature review
• Report of the systematic data analysis (pilot study)
• Study protocol for the planned confirmatory prospective randomised controlled trial, including the statistical analysis plan
• Summarised evaluation / discussion

3. study design:

• Prospective, randomised controlled trials (RCTs) are more promising (as of 2024), but retrospective studies with control groups are also possible.
• Comparison with standard care from the real-life performance of the German statutory health insurance funds or another relevant intervention.
• The study population must be representative of the target population of the DiGA.
• The expected effect must be demonstrable within the duration of the study.
• Measures must be implemented to ensure data quality and integrity.
• Ethical and data protection aspects must be taken into account.

4. patient-relevant endpoints:

• Definition of endpoints that are intended to demonstrate the positive healthcare effect (e.g. faster recovery, reduction of symptoms). Patient-relevant endpoints that demonstrate a medical benefit or a patient-relevant improvement of structure and processes must be investigated.
• Recognised validated assessment instruments for the disease and the selected endpoint

From our own experience, the BfArM almost exclusively recognises proof of medical benefit.

Please note: For DiGA of risk class IIb, only a medical benefit must be proven in accordance with the regulations of the Act to Accelerate the Digitisation of the Healthcare System (Digital Act - DigiG).

Final inclusion

For final inclusion in the DiGA Directory, the manufacturer must prove the positive healthcare effect by means of a completed study. This study must comply with scientific standards and the results must be significant and relevant.

‍Requirements(not comprehensive):

1. completed study within 12 months of provisional inclusion in the DiGA Directory:

• A prospective, randomised controlled trial (RCT) is the expected gold standard, which can only be deviated from in very well justified individual cases.
• Presentation of the target population
• Compliance with the protocol
• Consistency with the data from the systematic data analysis
• Evidence of adherence to standard therapy

2. patient-relevant endpoints:

• Evidence of medical benefit or patient-relevant improvement of structure and processes.
• Endpoints must be clearly defined and measurable with validated measurement instruments
• The effect size of the intervention must be above the threshold value for clinical relevance (minimal clinically important difference, MCID)

3. data quality and integrity:

• Ensuring data quality and integrity through appropriate measures.
• Transparent and complete reporting of study results.
• Evidence of DiGA utilisation in the intervention group
• Sufficiently high retention rate (small number of dropouts)
• Monitoring

4. statistical significance:

• The results must be statistically significant and have a sufficient number of cases.
• Compliance with the statistical analysis plan
• Persons mapped in subgroups with sufficient frequency (subgroup analyses meaningful)

5. ethical and legal aspects:

• Compliance with ethical standards and authorisation by an ethics committee.
• Compliance with data protection regulations.

6. transparency and registration:

• Registration of the study in a public study register recognised by the WHO, e.g. DRKS or clinicaltrials.
• Publication of the study results in a scientific journal.

The mere collection of data or the detection of diseases alone is not recognised as a positive healthcare effect. The DiGA must demonstrably lead to an improvement in the care or health status of patients.

To fulfil the complex requirements for DiGA studies and achieve successful inclusion in the BfArM Directory, contact MEDIACC for an initial consultation. Our experts will support you in planning and conducting high-quality clinical investigations that meet the strict criteria and optimally position your DiGA.

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(Status 2023, updated May 2024)