Decentralised Clinical Trials for Food Supplements
Does a Hybrid RCT Suffice to Defend a Health Claim Before the Polish Chief Sanitary Inspectorate (GIS)?

Regulation (EC) No 1924/2006 on nutrition and health claims made on foods requires that every health claim be based on and substantiated by generally accepted scientific evidence. But what does this mean in practice when data-collection methodology is evolving faster than EFSA guidelines? The answer is uncomfortable: the manufacturer bears the regulatory risk alone, and the supervisory authority — the Polish Chief Sanitary Inspectorate (GIS) — does not need to wait for scientific consensus before issuing a decision ordering the removal of a claim.

What a Decentralised Clinical Trial Is — and Why This Is Not Merely a Methodological Question

A Decentralised Clinical Trial (DCT) is a clinical trial in which some or all of the research procedures take place outside a traditional clinical site — at the participant's home, via a telemedicine platform, or through wearable devices collecting data in real time. The hybrid model combines in-person visits (e.g. randomisation, blood sampling) with remote elements (electronic diaries, remote blood pressure monitoring, video consultations with the investigator).

For a food supplement manufacturer, this distinction has a direct bearing on one specific legal problem: does a trial conducted under a DCT or hybrid model meet the standard of 'generally accepted scientific evidence' set out in Article 5(1)(a) of Regulation (EC) No 1924/2006? In its guidelines on the substantiation of health claims — in accordance with the principles for the assessment of scientific evidence applied by the EFSA NDA Panel (series of guidance documents from 2011 onwards) — EFSA sets out a hierarchy of evidence in which the RCT (randomised controlled trial) occupies the highest position. However, the 2011 guidelines did not anticipate that an RCT could be conducted via a smartphone application.

Terminological note: This article uses the term 'clinical trials for supplements' in the industry-standard sense. Formally, studies on food supplements are not 'clinical trials' within the meaning of Regulation (EU) No 536/2014 (Clinical Trials Regulation), which applies exclusively to medicinal products. The precise term is 'interventional human studies'. This distinction is relevant in administrative proceedings and before courts.

Expert Tip: Before commissioning a DCT or hybrid trial, the manufacturer should obtain a written methodological opinion from a biostatistician with experience in EFSA procedures — not from the CRO selling the service. The opinion should directly address whether the trial protocol complies with the principles for the assessment of scientific evidence applied by the EFSA NDA Panel (series of guidance documents from 2011 onwards) and whether it meets the ICH E6(R3) criteria (2023 version) with respect to electronic data integrity.

Where the Law Is Silent: The Gap Between Regulation (EC) No 1924/2006 and the Reality of DCTs

Regulation (EC) No 1924/2006 does not define which clinical trials are acceptable as a basis for substantiation. It refers to 'generally accepted scientific evidence' — a deliberately broad concept whose content EFSA fills through scientific opinions issued in the context of authorising specific claims. This means that the standard is in practice shaped by EFSA on a case-by-case basis, rather than by a single uniform legislative act.

For DCTs, the situation is as follows: the European Medicines Agency (EMA) published in December 2022 the Recommendation paper on decentralised elements in clinical trials, addressing clinical trials of medicinal products. However, those guidelines apply to medicinal products, not to food. EFSA has not yet published any position paper directly addressing the acceptability of DCTs as a basis for the substantiation of health claims for food and food supplements.

• Regulation (EC) No 1924/2006, Article 5(1)(a): requirement for 'generally accepted scientific evidence' — no definition of trial methodology
• EFSA NDA Panel principles for the assessment of scientific evidence (series of guidance documents from 2011 onwards): the evidence hierarchy assumes RCTs conducted in in-person settings
• EMA Recommendation paper on decentralised elements in clinical trials (December 2022): applies exclusively to medicinal products, not to food
• ICH E6(R3) (2023): updated GCP guidelines accommodate DCTs, but GCP is a standard for medicinal products, not food supplements
• Gap: no EFSA or European Commission document directly regulating DCTs for food

This gap is not neutral for the manufacturer. In the event of a GIS inspection or administrative proceedings, it is the manufacturer who must demonstrate that its substantiation meets the standard under Article 5(1) — the burden of proof lies with the party relying on the claim, not with the authority. The authority may challenge a DCT-based trial by citing the absence of recognition of that methodology by EFSA, without being required to show that the trial was scientifically flawed.

Data Integrity as the Flashpoint: Where DCTs Are Most Vulnerable Before a Regulatory Authority

The greatest practical risk in substantiation based on a DCT is not the remote nature of the trial itself, but the question of data integrity. When assessing substantiation, EFSA analyses, among other things, participant compliance, the risk of bias, and the reliability of the effect measurement. In a DCT model, primary data are collected by the participant — via an application, a wearable device, or an online questionnaire. The question an authority may ask is: who verified, and how, that the trial participant was actually taking the product rather than simply clicking 'yes' in the application?

In a traditional RCT, compliance is verified by the investigator (tablet counts, measurement of substance concentration in blood). In a DCT, it is often based solely on participant self-reporting. In its scientific opinions, EFSA has on multiple occasions questioned trials with low compliance verification — for example, in scientific opinions on dietary fibre and satiety from 2010 and subsequent years — and has treated this as grounds for downgrading the reliability of the evidence.

Expert Tip: A manufacturer commissioning a DCT should include in the trial protocol at least one objective compliance marker that can be verified remotely or during in-person monitoring visits — for example, measurement of a biomarker in blood at weeks 4 and 8 of the intervention. The absence of such a marker in the protocol provides a ready-made argument for the Polish Chief Sanitary Inspectorate (GIS) or EFSA to challenge the reliability of the trial as a basis for substantiation.

graph TD
    A[Manufacturer plans a health claim] --> B{Type of claim}
    B -->|Art. 13 list 432/2012| C[Uses an authorised claim]
    B -->|Art. 13(5) or Art. 14| D[Requires EFSA authorisation]
    B -->|Art. 13 own substantiation| E[Substantiation on the shelf - risk of GIS inspection]
    C --> F[Substantiation required in case of inspection]
    D --> G{Trial methodology}
    E --> G
    F --> G
    G -->|Traditional in-person RCT| H[Compliant with EFSA 2011 guidelines]
    G -->|Hybrid DCT model| I[No EFSA precedent for food]
    H --> J[Low regulatory risk exposure]
    I --> K[High exposure - no guarantee of acceptance]
    K --> L[Recommendation: pre-submission consultation with EFSA]
    I --> M{Critical DCT elements}
    M --> N[Compliance verification - objective marker]
    M --> O[Maintenance of blinding - risk with supplements]
    M --> P[Electronic data integrity - ICH E6 R3]
    N & O & P --> Q[DCT protocol ready to defend before GIS/EFSA]

The Hybrid Model and the Requirements for Randomisation and Blinding: What EFSA Actually Examines

In its 2011 guidelines (in accordance with the principles for the assessment of scientific evidence applied by the EFSA NDA Panel), EFSA places the double-blind RCT at the top of the evidence hierarchy. The hybrid model does not preclude either randomisation or blinding — but it makes them harder to maintain. Consider the following scenario: randomisation takes place during the only in-person visit, but blinding is maintained solely through an IT system managing the delivery of the investigational product and placebo to the participant's home. If a participant in the placebo group identifies from the taste or texture of the product that they are not receiving the active substance, blinding is broken, and EFSA may classify the trial as open-label or single-blind — which automatically lowers its position in the evidence hierarchy.

• Randomisation in DCTs: feasible and acceptable if centrally managed by an independent system (IWRS/RTSM)
• Blinding in DCTs: high risk for products with a distinctive taste, smell, or texture — typical of food supplements based on botanical extracts
• Allocation concealment: in the hybrid model, must be documented in both the protocol and the final report
• ITT (intention-to-treat) analysis: EFSA prefers ITT; with high dropout rates in DCTs, ITT analysis may show no effect even where per-protocol efficacy is good
• Sample size: DCTs often enable recruitment of larger groups — but EFSA assesses quality, not merely numbers

Manufacturers often argue that the larger sample sizes achievable in DCTs compensate for potential methodological limitations. This is a mistake. EFSA has on multiple occasions rejected substantiations based on large but methodologically weak trials — a clear example being the series of negative scientific opinions on probiotics issued between 2011 and 2013, in which dozens of applications were rejected despite large cohorts, precisely because of insufficient control of confounding variables.

It should be emphasised, however, that a well-designed hybrid model incorporating objective biomarkers, central in-person visits, and validated electronic tools can be scientifically acceptable. EFSA assesses the methodological quality of a study, not its operational form. If a hybrid protocol minimises bias, provides reliable compliance verification, and employs hard endpoints, there are no formal grounds for rejecting it solely because it utilises remote elements.

For context, it is worth noting that in the United States, the FDA issued updated guidance on DCTs in 2023 (Decentralized Clinical Trials for Drugs, Biological Products, and Devices), reflecting a global trend towards acceptance of technology that outpaces regulation. However, EU food law is more conservative than pharmaceutical law in both the American and European contexts. A supplement manufacturer cannot assume that acceptance of DCTs in the medicinal products context will automatically translate to acceptance in the context of health claim substantiation for food before EFSA.

Substantiation Under Article 13 vs Article 14 of Regulation (EC) No 1924/2006: Different Evidentiary Standards, Different DCT Risks

Regulation (EC) No 1924/2006 distinguishes between two categories of health claims. Article 13 covers claims based on generally accepted scientific evidence, authorised on the EU list (Commission Regulation (EU) No 432/2012). Article 14 covers claims relating to the reduction of disease risk and claims referring to children's development and health — these require individual authorisation by EFSA and the European Commission.

For a manufacturer relying on a claim from the Article 13 list (Regulation (EU) No 432/2012), a DCT carries different implications than for a manufacturer seeking Article 14 authorisation. In the case of Article 13, the manufacturer does not need to submit a dossier to EFSA — it merely needs to hold substantiation in readiness for a GIS inspection. Here, a DCT-based trial may be sufficient, provided the manufacturer can demonstrate that it meets the standard set out in the EFSA 2011 guidelines. In the case of Article 14, a DCT-based trial must undergo formal EFSA assessment — and here, the absence of any precedent of a positive EFSA scientific opinion based solely on a DCT represents a real risk of application rejection.

• Article 13 of Regulation (EC) No 1924/2006 + list under Regulation (EU) No 432/2012: substantiation held 'on the shelf', without submission to EFSA; DCT as an element of substantiation — risk arises at GIS inspection
• Article 14 of Regulation (EC) No 1924/2006: mandatory EFSA authorisation procedure; DCT as the basis of a dossier — risk of rejection due to absence of precedent
• Article 13(5) of Regulation (EC) No 1924/2006 (new claims based on newly developed scientific evidence): procedure similar to Article 14; DCT subject to full EFSA assessment

Expert Tip: A manufacturer planning to apply for Article 14 authorisation on the basis of a DCT should, before submitting the application, make use of the pre-submission consultation procedure with EFSA (available under Article 16 of Regulation (EC) No 1924/2006 in conjunction with EFSA's administrative procedures). This is the only formal route to ascertain in advance whether EFSA will accept the DCT methodology in a specific case — rather than discovering the problem after two years and several hundred thousand euros spent on the trial.

graph LR
    subgraph RCT_STACJONARNY[Traditional In-Person RCT]
        R1[Compliance: verified by investigator]
        R2[Blinding: controlled at site]
        R3[Data: collected by site staff]
        R4[EFSA precedent: numerous positive scientific opinions]
        R5[Cost: high]
        R6[Recruitment: geographically limited]
    end
    subgraph DCT_HYBRYDOWY[Hybrid DCT Model]
        D1[Compliance: self-reporting + optional marker]
        D2[Blinding: risk of unblinding during home delivery]
        D3[Data: mobile application / wearable device]
        D4[EFSA precedent for food: none]
        D5[Cost: 30-50% lower]
        D6[Recruitment: multi-site, multi-country]
    end
    subgraph RYZYKO[Regulatory Risk Assessment]
        X1[Low exposure at GIS inspection]
        X2[High exposure - no established standard]
    end
    RCT_STACJONARNY --> X1
    DCT_HYBRYDOWY --> X2

What the Polish Chief Sanitary Inspectorate (GIS) Actually Inspects and What Decisions It May Issue

The Polish Chief Sanitary Inspectorate (GIS) and regional sanitary inspectorates supervise food supplements on the basis of the Act of 25 August 2006 on food and nutrition safety (Journal of Laws 2006, No. 171, item 1225, as amended) and Regulation (EC) No 1924/2006. In the context of health claims, inspections cover verification of whether a claim appearing on a label or in marketing materials complies with the list of authorised claims (Regulation (EU) No 432/2012) or holds individual authorisation under Article 14.

The Polish Chief Sanitary Inspectorate (GIS) does not independently assess the methodology of clinical trials — it lacks the subject-matter expertise and resources to do so. In practice, the authorities rely on EFSA scientific opinions and the list of authorised claims. If a manufacturer uses a claim not appearing on the Regulation (EU) No 432/2012 list and asserts that it holds substantiation based on its own DCT, the authority may challenge the claim as unauthorised and order its removal by administrative decision. The penalty for using an unauthorised health claim is a fine under Article 103 of the Act on food and nutrition safety — up to PLN 5,000,000 or up to 3% of annual turnover.

Enforcement practice by the Polish Chief Sanitary Inspectorate (GIS) shows that authorities are increasingly moving beyond mere orders to remove a claim — they are more frequently initiating proceedings for the withdrawal of a product from the market or imposing a prohibition on placing it on the market, where the claim forms part of the trade name or constitutes a central element of the product description. In such cases, a DCT-based trial, even if methodologically sound, does not protect the manufacturer, because the authority is challenging not the quality of the trial but the very fact that the claim lacks authorisation.

Disclaimer: This article is for informational and educational purposes only. It does not constitute legal or scientific advice and does not replace an individual protocol analysis by a health claim substantiation expert or a lawyer specialising in food law. Each case requires a separate assessment taking into account the specifics of the product, the claim, and the target market.