The GCP guidelines are considered the international benchmark for ensuring data quality and participant safety, while also facilitating mutual recognition of clinical data across regulatory agencies. In January 2025, the ICH adopted the third revision of its GCP guidelines (“ICH E6 R3”), which are now structured into a set of general principles and an Annex I on implementation. These will come into effect in the EU on 23 July 2025. A second annex, focused on decentralised elements, is currently under review and is expected to take effect in early 2026.

Changes in risk assessment and management

Not all clinical trials involve the same level of intervention or carry the same degree of risk for participants. While some clinical trials investigate authorised medicines, others involve unauthorised products using more complex designs, including data collection devices or artificial intelligence (AI) tools for participant monitoring and data analysis.

Recognising this, the new GCP revision introduces a more flexible, risk-based approach tailored to the specific features of each trial. Sponsors must now anticipate potential risks and design the study in proportion to the level of risk expected. Clinical trial designs should avoid unnecessary complexity, excessive data collection, and undue burdens on participants and investigators.

Use of new technologies and decentralised clinical trials

The new version of the GCP guidelines reflect the growing digitalisation of clinical trials and include a dedicated section on data management (covering everything from collection to deletion). The use of technological solutions (e.g., digital tools, AI, remote monitoring, etc.) must be validated in advance, used transparently, and justified based on their purpose in the trial.

This shift is also reflected in the replacement of the term “CRO” (Contract Research Organisation) with the broader term “service providers.” This acknowledges that sponsors now outsource not only traditional functions like monitoring and data analysis, but also the implementation of innovative technological solutions. The GCP guidelines require any outsourcing to be properly documented and emphasise the sponsor’s responsibility to supervise all service providers involved in the trial.

Of note is Annex II, expected to enter into force in early 2026. It sets specific requirements for the use of decentralized elements and real-world data (RWD) in trial design. In line with the proactive risk-based approach, sponsors must justify their use and ensure participants are informed. These requirements are consistent with guidance already issued by various European regulatory agencies, including the Spanish Agency of Medicines and Medical Devices (AEMPS).

Practical recommendations for sponsors and CROs

The third revision of the GCP rules makes it necessary for sponsors to review and update their internal procedures and strengthen coordination with service providers.

A key aspect of GCP compliance is being prepared for inspections by national authorities. In Spain, the responsibility for GCP inspections is shared between the AEMPS and the regional health authorities. According to its 2024 activity report, the AEMPS is one of the most active European agencies in GCP inspections requested by the European Medicines Agency (EMA).

Therefore, sponsors are advised to pay close attention to the requirements under the new GCP revision, especially for complex, multicentre, or technology-driven clinical trials. In such cases, it will be essential to: (i) justify the use of digital tools or AI in line with the trial design; (ii) properly document their validation; and (iii) ensure transparent implementation. Moreover, active supervision of all involved service providers and CROs will also be essential to ensuring full compliance with GCP requirements.

La entrada Updates on Good Clinical Practice Guidelines (ICH E6 R3) aparece primero en Faus Moliner.

At European level, some regulations have been adopted in this regard. In the case of Spain, the Spanish Agency for Medicinal Products and Medical Devices (AEMPS) has modified the document of instructions for conducting clinical trials in our country on several occasions to include some measures in this regard. Initially, it was expected that these measures would be maintained until the World Health Organisation declared the end of the pandemic. However, given the positive experience gained, especially for patients, it was considered appropriate to facilitate the use of these decentralised elements in clinical trials, beyond the existence of a health crisis. To this end, the European Commission, the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) have issued the Recommendation Paper, which we will analyse below.

Equivalent guarantees

The Recommendation Paper provides a set of guidelines on how and under what conditions it is acceptable for certain elements of clinical trials to be conducted in a decentralised manner. All these guidelines, which should be taken into account by sponsors when designing and conducting such trials, revolve around one basic principle: in decentralised clinical trials, the safety and rights of trial participants and the reliability of data should be ensured to at least the same extent as in a “traditional” clinical trial, i.e., one that is conducted entirely within a healthcare centre facility. For the same reason, it is also advisable that, when the sponsor prepares his trial with decentralised elements, the investigators and other healthcare professionals involved in the care of the patients participating in the trial should also be consulted.

“Enhanced” obligations of the sponsor

For decentralised trials, the sponsor should adequately identify all decentralised elements in the trial documents, particularly the protocol, so that they can be properly assessed by the regulatory authorities. It is also the sponsor’s responsibility to assess the specific risks associated with the decentralised processes it intends to implement, and the measures it intends to take to mitigate those risks.

In addition, it is very common for decentralised trials to involve other service providers, such as nurses who can perform certain actions in the patient’s home, or IT service providers responsible for the telematic management of the trial data. It is therefore crucial that the roles and responsibilities of the sponsor, investigators, and other stakeholders are well defined, and that any delegation of tasks is contractually agreed.

Informed consent

In the process of obtaining informed consent, face-to-face communication between the potential trial participant and the investigator is considered essential. Therefore, if such communication is conducted remotely, it is recommended that this takes place in real time, where both can see and communicate with each other, with audio and video, and also check their identities. With regard to signature, informed consent can be signed either by handwriting or by digital signature, provided that the signing process, including the validity of the signatures, can be reconstructed and its security and confidentiality can be guaranteed.

On the other hand, the greater number of parties involved in decentralised trials and the apparent delocalisation of the activities carried out make it necessary to pay special attention to compliance with the rules on the protection of personal data.

Home interventions

Where home delivery and/or home administration of the IMP is planned, the sponsor’s risk assessment of the appropriateness of these measures should consider, among other things, the safety profile of the product, the route of administration/preparation requirements, the trial population, and the logistics of delivery and storage conditions. In any case, the sponsor retains overall responsibility for the supply process and the arrangements to be made with the parties involved in the supply process. It is recommended that a healthcare professional should always be involved in the home administration of the product in the case of complex administrations, where special preparation or handling is required, or where the safety profile of the product so requires. In all cases, procedures will be established to verify patient compliance and to manage product returns.

If any other trial-related procedure (e.g., collection of biological samples) is to be performed at the patient’s home, it may be performed if it does not pose an additional risk to the patient or to the reliability of the data, and in any case if the person performing the task is qualified and/or trained to do so. Any harm to the patient as a result of a procedure performed at home must also be covered by the appropriate insurance policy or equivalent guarantee.

“Living” reference document

Given the rapid advances in the field of decentralised clinical trials, it is expected that this recently published Reference Paper will evolve over time as new “real-life” data from experience in this area become available. For the time being, this paper can be a good reference to confirm that a clinical trial with decentralised elements is ethically and legally acceptable, both for sponsors wishing to conduct such trials and for the ethics committees and regulatory authorities that have to approve them.

La entrada Guidelines to facilitate the conduct of decentralised clinical trials of medicinal products in the European Union aparece primero en Faus Moliner.

Against which company should damages claims be brought?

Damage claims should be brought against the sponsor of the clinical trial or the entity acting as its legal representative. In the case under analysis, the Court of Appeals dismisses the claim on the grounds that such claim was filed against the Spanish subsidiary of the sponsor rather than against the sponsor or its legal representative. Although the Spanish subsidiary belonged to the same group of the sponsor, it was not its legal representative (such representative was another company of the group domiciled at the Netherlands). On the other hand, the Spanish subsidiary had not connection with the clinical trial.

Furthermore, the Court states that the veil piercing doctrine cannot be applied since both the Spanish subsidiary and the sponsor were independent entities with distinct activities, and no fraudulent intent to evade liability appeared to exist.

Expert evidence

Despite considering that the Spanish subsidiary could not be sued, the Court analyses the merits of the case. The Court concludes that there is no causal link between the alleged damaged and the tested drug. This conclusion is reached on the basis of an expert report provided by the defendant and a report issued by a court-appointed expert.

Rules governing clinical trials state that damages caused to individuals participating in a clinical trial are presumed to derive from such clinical trial if they occur during the clinical trial or throughout the year following the same. This presumption, however, may be displaced by fact-based evidence showing that the damages did not result from the clinical trial itself but rather from other causes such as the evolution of the patient’s illness. The Court emphasises that expert reports are a key piece of evidence to displace this type of presumptions.

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In March 2017, under Law 19/2013, on Transparency, Access to Public Information and Good Governance, an association of consumers and users requested the Spanish Ministry of Health,  Social Services and Equality (MOH) to provide them with statistics of prescription and annual cost of certain medicinal products (price, number of prescriptions, total annual cost, financed cost); as well as with the raw data of the clinical trials on the basis of which their marketing authorisation was granted. Given the refusal of the MOH to provide such information, Scabelum exercised its right to submit a complaint before the CTBG.

Access to economic data

In its allegations before the CTBG, the MOH pointed out that the information could not be provided since it could be detrimental to legitimate economic and commercial interests, invoking therefore one of the limits that permit refusal of access in accordance with Law 19/2013.

The CTBG, in its resolution, criticizes the fact that the MOH refuses access without properly explaining the reasons for which it understands that providing access could be detrimental to the economic and commercial interests of a company, reiterating its doctrine in the sense that, in order to benefit from this derogation foreseen in Law 19/2013, the administration must apply criteria of proportionality and must properly analyse the circumstances of each specific case.

The CTBG understands that providing the association with the requested information cannot cause any harm to the companies involved due to its statistical nature and because the MOH publishes, on its web page, statistics of consumption and pharmaceutical expenditure based on prescriptions of the National Health System.

On the other hand, we should recall that the doctrine of the CTBG (Resolution of 5 of November of 2015) is that the MOH must not provide access to the economic and financial data that the pharmaceutical company has offered to the administration when requesting the authorisation for the price of the product.

Access to the clinical trials data

Regarding the clinical trials that justify the marketing authorisation, the CTBG establishes that it must be the AEMPS who must respond to the request as it is the competent body, highlighting that the MOH should have transferred the request to the AEMPS for processing. Likewise, the CTBG recalls that the Spanish registry for clinical trials exists since January 2016 and that it contains information about the way the trial is conducted and also information regarding its results.

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Simplification of the process

The procedure to obtain the authorisation to start a trial, or to make a substantial change to the conditions under which such authorisation is originally granted, have been simplified considerably, in particular for low-intervention clinical trials. The most noteworthy new feature, in addition to a shortening of timescales, is that an opinion need only be sought from one Ethics Committee (now known as Research Ethics Committee) rather than one per participating centre, as had been the case up until now. This change will lead to obvious time savings in the procedure, in addition to a reduction in costs as only one fee shall be paid as part of the assessment of the trial, regardless of whether several Committees are involved in said process.

Importance of the contract

Another important new aspect involves the contract that the sponsor must sign with each centre participating in the trial. Historically, the negotiation and signature of contracts has been a nightmare for sponsors, often leading to delays in starting trials. The Royal Decree seeks to speed up this process by implementing two measures. First, it calls on the competent health authorities to agree on just one valid contract template for the entire National Health System (SNS), the drafting of which is based on the general principles established by the Interterritorial Council of the SNS. And second, it allows for the contract to be executed at any time, and not solely upon authorisation of the trial, as had been the case up until now. In the event that the contract is signed before the trial is authorised, the regulation sets out that the contract will not become effective until authorisation is obtained.

Figure of the sponsor

The contract is particularly important when the sponsor decides to delegate all or part of its duties to a third party, such as a CRO. Thus, special care must be taken to appropriately document which tasks have been delegated and the scope of liabilities must be defined.

La entrada New rules for carrying out clinical trials in Spain: in a faster, safer and more transparent way aparece primero en Faus Moliner.

As a result of an anonymous complaint made before the Spanish Agency of Medicinal Products and Medical Devices (AEMPS in Spanish), an infringement procedure was initiated against a physician claiming that he had carried out a clinical trial, acting as sponsor and principal investigator, without obtaining prior approval, without having received a favorable ruling from the CEIC, and having obtained the informed consent of the patients by providing them with information that was not accurate. The Autonomous Region of Madrid imposed a fine of 216.003 Euros. The judgment confirms the fine.

Differences between a trial and an observational study

The core of the discussion before the Court was establishing whether the study of Dr. Soriano was a trial or a prospective observational study. The judges analyzed in detail the differences between both concepts; and they came to the conclusion that when a medicine is used under conditions different from those that are set forth in its SmPC one cannot speak of a post-authorization observational study. In this sense, the judgment points out that in an observational study medicines must be prescribed in accordance with the normal conditions of clinical practice, and that according to the rules governing these studies such normal conditions are those established in the marketing authorization.

Before reaching this conclusion, the judgment establishes that a medicinal product used under conditions different from those authorized becomes a medicinal product under investigation; reproducing thus the provisions of Royal Decree 1015/2009. Therefore, it is convenient that those who use medicinal products under conditions different from those authorized adjust strictly to legal rules and handle with the utmost care any activity that might be considered as clinical investigation. As the judgment says neither the medical practice nor the professional freedom of prescription of the physician protect, under any circumstances, the performance of unauthorized clinical trials.

Off label use

On the other hand, the judgment is a wake-up-call for those who favor the use of medicinal products under not authorized conditions. The judgment refers to this use recalling the provisions of Royal Decree-law 16/2012 regarding the sustainability of the National Health System, highlighting that the prescription of medicinal products and medical devices must be made in the most adequate way in benefit of the patients and that off label use must be authorized previously by the commission responsible for the therapeutic protocols in each Autonomous Region.

The Court also recalls that this applies even if the medicinal product is used in the approved indications but with a dosage different from the one authorized.

La entrada Important fine to an investigator that promoted a clinical trial without administrative approval aparece primero en Faus Moliner.

Through these changes the Ministry aims at  anticipating the new European regulation on this matter which is foreseen to be issued in 2014, and which seeks to facilitate research in the  territory of the European Union. Due to its interest, we will briefly summarize some of the most relevant novelties.

Simplification of procedures

The main objective of the draft is to simplify the procedure for obtaining the authorization necessary to implement a clinical trial in Spain. With this aim, it is foreseen to improve the coordination between the Spanish Agency for Medicinal Products and Medical Devices (AEMPS) and the new Evaluation Committees for Research with medicinal products –that will progressively replace the current Clinical Research Ethics Committees– in order to avoid duplicities in the process of evaluation of the trial.

Likewise, the long expected “single ruling” shall be finally implemented. The principle of mutual recognition, deeply ingrained in European pharmaceutical law, has finally arrived to the rulings with regard to clinical trials. In this way, the ruling issued by the Evaluation Committees for Research with medicinal products chosen by the sponsor shall have to be accepted by the rest of the committees involved in the trial. Other measures along the same line are the introduction of the figure of the “low risk clinical trial”, for which there will be less burdensome requirements, the introduction of a single point of contact between the sponsor and the authorities, or the generalization of the use of electronic media in the communications between the two.

More transparency

More and better information on clinical trials carried out in our country will be put at the disposal of the public, through the creation of a state registry of clinical trials. Such registry, which will be managed by the AEMPS, shall allow for more transparency and will provide interested patients with the possibility to participate in the trials that will be started.

A single contract model

The plan to implement a single contract model to be used in all public hospitals that depend on the National Health System should also be emphasized.

It is moreover foreseen that the signing of such  contract between the centre and the sponsor should take place in a period of 60 days. However, and since there are no implications involved in case that such term is exceeded, we will have to wait for the approval of the draft to see how effective this mandate is.

La entrada The Ministry releases the draft for the new regulation on trials with medicinal products and medical devices aparece primero en Faus Moliner.