Decentralised and remote clinical trials: evolving legal framework

Anna Wiktorow-Bojska
WKB, Warsaw
anna.wiktorow-bojska@wkb.pl

The 21st century trend for remote working has come to the area of clinical trials – and the Covid-19 pandemic has only accelerated the process. Many sponsors are moving away from the traditional clinical trials with onsite follow-ups and multiple protocols to follow, which require patients to travel long distances. Today, many clinical trials are decentralised: either fully or partially remote. This has resulted in multiple new requirements, and in legislators needing to keep up with these concepts to ensure safety of patients and their data.

The Global Health Network’s International Council for Harmonisation (ICH) Good Clinical Practice guidelines are applicable to almost all clinical trials conducted globally. In addition, the United States Federal Food, Drug and Cosmetic Act includes direct references to decentralised and/or remote clinical trials – clearly allowing such clinical trials to be performed.

The European Union Clinical Trials Regulation does not include such a reference but the European Medicine Agency (EMA) has issued a recommendation paper on decentralised elements in clinical trials and, together with the European Commission, it has launched an initiative called Accelerating Clinical Trials in the European Union (ACT EU) which also aims at facilitating decentralised clinical trials in the EU.

New guidelines and legislation are published on a regular basis, but sponsors, contract research organisations (CROs) and investigators need also to take into consideration other rules regulating data protection, artificial intelligence, medical devices, healthcare, medical professionals and more.

Regardless of the details of the above regulations, what they all have in common is that whenever a decentralised and/or remote (even partially) clinical trial is at the planning stage, the patients’ safety and the type of trial needs to be taken into account. The selected solutions must reflect the clinical trial and the risks associated with it.

What is detrimental for patients’ safety?

To determine whether a trial can be fully decentralised, remote or include remote elements, the sponsor and/or CRO must assess the safety profile of the trial, in particular:

• the stability of the investigational medicinal product (IMP);
• the storage requirements;
• the method of administering the IMP;
• the required observation after administration of the IMP; and
• the severity of potential adverse reactions and the necessity of the investigators being quickly available for their treatment.

All these elements should be assessed from the perspective of whether the planned approach to the clinical trial will impact the level of risk. If the decentralised or remote approach increases the risk for the participants’ safety, which cannot be mitigated in any way, then it should not be taken.

Similar assessment should also be made in order to ensure the reliability of the clinical trial results.

What about informed consent?

Informed consent can be obtained remotely; this is often called eConsent. Obtaining remote consent does not release the investigator from complying with the requirements applicable to informed consent being taken in person. Therefore, the process of gaining informed consent remotely has to be organised in a way to ensure that:

• the participants give it freely, without any influence of third parties;
• the participants are fully informed, had the opportunity to ask any questions they may have and have had any doubts clarified;
• it is properly documented and archived;
• it is supervised by the principal investigator and not fully delegated to any local healthcare professional or other third party; and
• the identity of the participant is verified in a reliable and certain manner.

How to protect sensitive and confidential data?

The data transferred in the decentralised and/or remote clinical trials often constitutes sensitive and confidential data. Therefore, when planning such clinical trials, sponsors and CROs have to consider General Data Protection Regulation (GDPR) requirements if any EU participants are involved in the clinical trial, as well as any other personal data protection rules that could apply to the given trial.

The location of the server where the data will be stored is crucial. For example, if the server is outside of the European Economic Area and EU participants are involved, proper documentation associated with transferring the data outside of the EEA will be necessary. This includes the proper wording of the personal data processing forms for participants, as well as transfer impact assessments.

From the perspective of both sensitive and confidential data, meeting the cybersecurity requirements is crucial for the organisation of the decentralised and/or remote clinical trial. For the EU, sponsors and CROs should consider the NIS2 Directive and the applicable laws implementing these rules (eg, the Polish implementing statute (not yet adopted) is much more restrictive than the NIS2 Directive in the healthcare area).

Is home delivery possible for investigational medicinal products?

The possibility of delivering IMPs to participants’ homes depends on local rules. The US Food and Drug Administration (FDA) expressly allows such deliveries, particularly if the patients’ safety will be higher if they stay at home rather than visit a site. The EU guidelines indicate that it is possible if the national rules allow it.

Many risks can be mitigated if the investigational medicinal products are delivered by healthcare professionals and administered by them or in their presence. If properly organised, such a delivery could be considered as a home doctor visit instead of an IMP delivery.

For example, in Poland, the home delivery of prescription medicines is not allowed but doctors can administer medicinal products during a home visit. There is no exception for this rule for clinical trials.

Another issue to consider is delivery of IMPs from one warehouse to all clinical trial participants, regardless of their country of residence. Even in the EU, this will not always be possible, despite the free movement of goods principle. Some countries require a national pharmaceutical wholesaler or site pharmacies to be involved; therefore it might be not possible in all countries where the clinical trial is performed.

Do the rules on telemedicine apply?

Even in clinical trials, the rules on providing healthcare services apply. Therefore, any rules applicable to telemedicine services also apply to remote and decentralised clinical trials. If there are any local requirements for such services, they should be considered during the preparation of the clinical trial protocol and investigators’ brochure.

Although some deviations from the applicable rules are possible in clinical trials, they have to be approved by the ethics committee. The committee still has to ensure that the professional ethics are followed and that professional due diligence can be followed.

Does the software and other tools used in the trial have to be classified as medical devices?

There is no obligation for equipment, tools or software used in clinical trials – either stationary, decentralised and/or remote – to be classified as a medical device. If the software and hardware are used in the clinical trial only to transfer, store, archive and process the data, and it does not assist in any way in diagnoses or treatment, it probably would not be classified as a medical device and can be safely used without notified body certification.

On the other hand, if the device is supposed to be used by a family member and/or the participant themselves and if the device is intended for professional use, the sponsor and/or CRO should consider that this may constitute the use outside of the intended purpose and certification. The device for this purpose would not be considered a certified medical device: its use would have to be allowed by local rules and clearly approved by the ethics committee and competent authorities.

What is the future for decentralised and remote clinical trials?

The decentralised and remote clinical trials are becoming more popular. The fact that the Good Clinical Practice (or at least remote elements) allows such trials is crucial for performing them. This could allow cross-border trials, making them available to patients all over the world and lowering their costs.

However, national rules often limit the possibilities; therefore, national governments should be encouraged to follow the international rules or to create their own appropriate local laws.

One thing is certain – the development of legislation should not hinder progress in clinical trials, thanks to which more and more people have access to advanced therapies without having to leave their homes.