Decentralised clinical trials (DCTs) are research projects in which the digital recording and/or transmission of data related to trial interventions plays an important role. This may involve digitally recruiting trial participants, conducting trial visits in a patient’s home using telemedicine, or digitally recording and transmitting data using wearables (i.e. computer technology worn on the body) or smart devices such as tablets or smartphones. Digital technologies also affect other aspects of trials such as informed consent, monitoring, and the associated verification of source data. Another characteristic of DCTs is the delivery of the investigational medicinal product (IMP) directly to a trial participant’s home, where it is stored and, in some cases, administered by qualified trial nurses. Wherever possible, trained trial nurses perform and document trial-related interventions that take place in a participant’s home.
In hybrid DCTs, some procedures are performed in the conventional setting of a trial site, while others are performed in a decentralised setting at a participant’s home by a general practitioner or in a laboratory near the participant’s home. Whether parts of a clinical trial can be conducted in a decentralised setting depends on many factors, including the type of disease, the phase of the trial, and the type of investigational medicinal product as well as the applicable regulatory framework.
Regulatory framework for decentralised clinical trials
In Switzerland, clinical trials with medicinal products are regulated in the Therapeutic Products Act (TPA), the Human Research Act (HRA), and their associated ordinances. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH GCP) E6(R2) is also applicable in Switzerland (as set forth in Art. 5, para. 1 of Switzerland’s Clinical Trials Ordinance (ClinO)). With the new ICH GCP E6(R3) (currently under revision), a whole new Annex 2 will be added specifically covering decentralised elements, among other topics.1 Clinical trials must also fulfil the requirements of the Switzerland’s Data Protection Act (FADP) and Data Protection Ordinance (DPO).
Challenges facing decentralised clinical trials
One of the key challenges for sponsors and investigators is to ensure the oversight of all involved parties. The delegation of tasks and functions to third-party service providers should be defined in written agreements. In addition, all individuals performing trial-related tasks must have the appropriate training.
As with traditional clinical trials, the investigator is responsible for ensuring adequate medical care in the event that adverse events occur outside the trial site as well as the standardised documentation and protocol-compliant reporting of those events (ClinO, Art. 39–41; ICH GCP E6(R2), Section 4.3.2). The procedure for reporting adverse events should be defined in the protocol, and patients should receive documented training on how to report them (e.g. via a telephone call or an application on a mobile device). Furthermore, it must be ensured that the investigator is informed of adverse events in a timely manner so that he or she can decide what action to take.
If trial monitors review uncoded personal data from trial participants (e.g. medical records) as part of source data verification and this review is not performed in person at the trial site but instead by employing electronic tools to access the information from outside (i.e. remote source data verification (rSDV)), appropriate technical and organisational measures must be taken to ensure compliance with the Swiss Data Protection Act. For example, the source data may be accessed by using two-factor authentication and a virtual private network (VPN). The trial monitor may be granted read-only rights, and access must be restricted to trial participants only.
An active approach to DCT challenges
There is great interest, both internationally and in Switzerland, in performing DCTs. Swissmedic and swissethics published a joint position paper on DCTs that aims to encourage and invite stakeholders to intensify the dialogue on this innovative way of conducting clinical trials.2 The position paper considers the major challenges relating to DCTs. It is based on the current position of Swissmedic and swissethics and how they interpret their respective areas of responsibility (ClinO, Art. 25 and Art. 32). The existing legal framework already regulates many aspects of DCTs with medicinal products in Switzerland. However, researchers are recommended to liaise closely with Swissmedic and the ethics committees before setting up a DCT in order to clarify specific questions relating to the conduct of DCTs. Researchers should not hesitate to contact Swissmedic if they have any questions related to DCTs ().
References
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (2023) Final concept paper: ICH E6 (R3) guideline for good clinical practice annex-2 (version dated 30 March 2023, endorsed 28 April 2023). Accessed 31 July 2024: https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Annex2_ConceptPaper_2023_0405.pdf
- Swissmedic and swissethics (2022) Position paper on decentralised clinical trials (DCTs) with medicinal products in Switzerland (version 2.0 dated 15 December 2022). Accessed 31 July 2024: https://www.swissmedic.ch/dam/swissmedic/en/dokumente/bewilligungen/klv/positionspapier-dct.pdf.download.pdf/DCT_EN_.pdf
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