Decentralised clinical trials: key considerations for data management and monitoring

Camilla Appelgren
Mannheimer Swartling, Stockholm
camilla.appelgren@msa.se

Emmie Montgomery
Mannheimer Swartling, Stockholm
emmie.montgomery@msa.se

Alexander Mild
Mannheimer Swartling, Stockholm
alexander.mild@msa.se

Introduction

The landscape of clinical research is undergoing significant transformation. Decentralised clinical trials (DCTs) have emerged as an important development, accelerated by technological advances and the practical necessities imposed by the Covid-19 pandemic. This article examines the key regulatory and operational considerations associated with DCTs, focusing on data management and monitoring requirements. While the regulatory framework for DCTs is largely harmonised at European level, national contexts and strategic priorities shape how these trials are implemented in practice. This article therefore includes an examination of the Swedish perspective, which illustrates both the opportunities that DCTs present for countries seeking to enhance their competitiveness in clinical research and the practical challenges that arise from jurisdiction-specific regulatory requirements.

The development of decentralised clinical trials

Decentralised clinical trials represent a paradigm shift in how clinical research is conducted, offering new possibilities for patient participation while presenting novel regulatory and operational challenges. In a DCT, one or more elements of the trial are conducted outside the conventional trial site. Inter alia, data can be collected and analysed remotely using various digital tools.

The concept of DCTs is not inherently novel. Postal-based clinical trials have been conducted since the 1980s; however, technological advancements have meant that the tools and methodologies available today differ substantially from their predecessors.^[1] The adoption of decentralised elements in clinical trials gained particular momentum during the Covid-19 pandemic, which necessitated remote approaches and accelerated the development and validation of digital solutions.^[2]

Electronic Patient Reported Outcome (ePRO), ie, electronic patient self-reporting of outcomes, has been commonly used for some time. Reporting can take place, for example, via mobile apps, web forms or tablets. In addition, the development of various wearables such as bracelets, watches and rings has meant that health data can be collected directly from these devices, which is sometimes referred to as electronic Device Reported Outcome (eDRO). This means that objective data can be combined with patient-reported data and thereby provide a better basis for analysis.

The ability to perform certain aspects remotely offers significant advantages in terms of accessibility, facilitating patient recruitment, enhancing participant diversity and improving retention rates. Moreover, both financial and temporal costs can be reduced. At the same time, decentralised elements present new challenges, particularly with regard to monitoring and data management. Investigators must ensure that the data collected is accurate, and that it is handled securely and in compliance with applicable data protection regulations. The investigator must have control over and access to source data regardless of whether it is generated on-site, off-site or reported to the investigator.

Data management

Distribution of responsibilities and the role of participants

Decentralised clinical trials are distinguished by a significant transfer of data-gathering responsibilities from the investigator and their research site to the study participants themselves and/or those who care for them and/or external service providers (such as community nurses).^[3] The European Commission’s 2022 recommendation paper on decentralised elements in clinical trials (the ‘DCT Recommendation’) emphasises that the transfer of burden to trial participants must always be weighed against the potential benefits of the decentralised elements of the trial. Indeed, one of the key advantages of decentralising trials is to make it easier for patients to participate. This benefit is lost if too much workload is placed on trial participants.

When considering decentralising a clinical trial, a sponsor needs to weigh the benefits against the risks, and particularly consider whether scientific value and data integrity are affected. The DCT Recommendation emphasises that elements should not be decentralised to the patient’s home if this poses an increased risk to the participant or to the reliability of the data collected.

Technical prerequisites and equipment

A fundamental prerequisite for digital data collection is the proper functioning of the technical equipment. Technical problems with devices can lead to data being lost or not collected. To mitigate such risks, the DCT Recommendation advises that sponsors establish a risk mitigation plan for when digital tools do not work as intended. In addition, technical structures are important to keep data secure. Data transferred from the acquisition tool to the server should be encrypted to reduce the risk of unauthorised access. From an operational perspective, the sponsor also needs to consider how devices should be provided. The DCT Recommendation states that a participant who cannot or does not want to use their own device (phone, tablet, etc) should be offered an alternative by the sponsor. In other words, there should be no requirement for participants to use their own devices. On the other hand, the sponsor should also consider how to return equipment, taking into account that allowing participants to keep the digital tools used in the study could be considered as undue advantage.

Data quality and reliability

Another central aspect to consider in DCT is the reliability of data. It follows from the International Council for Harmonisation’s guideline for good clinical practice (ICH E6)^[4] that data collected during a clinical trial must be reliable and verifiable. This becomes particularly challenging in a decentralised clinical trial where data comes from several different sources. As mentioned above, it is important that digital tools function correctly to avoid technical sources of error. In addition, there is a risk that participants enter incorrect data (human error). The sponsor should take measures to minimise this risk.

A further consideration in ensuring data reliability is the challenge of filtering through available data. The use of digital tools means that it is now easier than ever to collect large amounts of data. Here, it may be appropriate to ask the question of what data is actually necessary and contributes to better analyses. Collecting too much data can result in unnecessary administration and even risk that the truly central data ends up being overshadowed. A focused approach to data collection, prioritising quality over quantity, is therefore essential.

Data protection and GDPR compliance

This principle of data minimisation is not only a matter of practical efficiency – it is also a fundamental requirement under the General Data Protection Regulation (GDPR). Questions regarding data privacy are particularly prominent in DCTs. Key GDPR principles such as data minimisation, purpose limitation and accountability require careful attention when data is collected across multiple locations and through various digital tools.

The DCT Recommendation says that particular emphasis should be placed on compliance with the GDPR when conducting DCTs. A clear division of responsibilities is required between the sponsor, investigator, and additional parties such as external healthcare personnel and providers of technology. In addition, it is important that access to trial data is controlled through defined user rights so that data can only be accessed by those who should have access to it. The DCT Recommendation recommends that unauthorised access should be prevented by using appropriate security measures, eg, firewalls.

Monitoring

While more data input pathways create the potential for a robust research basis, they also entail increased responsibility regarding oversight. When clinical trials move into participants’ homes, the sponsor’s and investigator’s responsibilities follow. They are responsible for trial participants’ safety, dignity and wellbeing. The fundamental responsibilities of sponsors and investigators are the same regardless of whether the trials are conducted in a decentralised manner or not.

The DCT Recommendation says there should be an established plan specifying the allocation of responsibilities of each party if critical safety data that needs immediate medical attention is discovered from digital tools. Furthermore, it emphasises that it is essential that participants understand how digitally transmitted information will be handled. For example, it must be clear to participants that the data is not monitored in real time and that participants must contact the investigator if they experience any specific safety concerns. It is also central that trial participants, investigators and service providers are trained in how to use the digital tools that will be used within the study.

The monitoring strategy should always be tailored to the specific circumstances of the trial in question. In particular, risks related to decentralised processes, tools, sites and persons should be incorporated into the monitoring strategy. A key consideration when monitoring participant compliance is the reduced physical interaction in DCTs. The investigator must account for the fact that few or no physical meetings take place between participants and the investigator and/or delegated staff.

The DCT Recommendation states that a combination of centralised and site monitoring is generally appropriate for DCTs. Site monitoring has historically been carried out on-site, but remote (off-site) monitoring has become more common, not least after the pandemic. According to the DCT Recommendation, remote access for the purpose of monitoring should be done according to the principles of necessity and proportionality, and the monitoring strategy should not unduly burden the site. However, the regulatory landscape varies across jurisdictions. Remote access to medical records is not currently permitted in Sweden, but it is in several other European countries.

National perspectives: the case of Sweden

The strategic importance of DCTs is increasingly recognised at national level, with several European countries establishing dedicated initiatives to strengthen their position in clinical trials and life sciences. Sweden provides an illustrative example of how countries are seeking to leverage DCTs to address challenges and capitalise on existing strengths.

Sweden has a history of research and development in the life sciences sector: it is one of the country’s largest export industries. One success factor has been a long tradition of collaboration between universities, industry and the healthcare sector. However, in recent decades, the number of clinical trials in Sweden has experienced a downward trend. In response, the Swedish government has commissioned the Swedish Medical Products Agency to establish Swetrial – a national partnership to strengthen Sweden’s role in clinical trials and life sciences. Facilitating and promoting the use of DCTs represents a key component of this strategy to reverse the declining trend, as decentralised approaches can make Sweden more attractive for international sponsors and more accessible for Swedish patients.

Sweden possesses certain unique competitive advantages that are particularly relevant in the context of DCTs. The country’s health data registers stretch back 70 years, and the long follow-up period combined with the ability to link data via personal identity numbers makes it possible to follow developments over time. This infrastructure complements the longitudinal data collection capabilities that DCTs enable through digital tools and remote monitoring. The combination of historical registry data and modern digital data collection methods offers significant potential for robust, long-term research.

At the same time, Sweden’s experience highlights some of the regulatory and practical challenges associated with implementing DCTs. As noted above, remote access to medical records for monitoring purposes is not currently permitted in Sweden, although it is allowed in several other European countries. This illustrates how national regulatory frameworks can impact the extent to which decentralised elements can be adopted, and underscores the importance of harmonisation efforts at European level.

The Swedish case demonstrates that while DCTs offer considerable opportunities – particularly for countries seeking to enhance their competitiveness in clinical research – successful implementation requires careful consideration of existing infrastructure, regulatory frameworks and the need for cross-sectoral collaboration. As DCTs continue to evolve, national initiatives such as Swetrial will play a crucial role in shaping best practices and addressing jurisdiction-specific challenges.

Conclusion

Decentralised clinical trials offer significant potential to enhance accessibility, efficiency and participant diversity in clinical research. However, realising these benefits requires careful attention to data management, robust monitoring strategies, and compliance with data protection regulations. As the Swedish example illustrates, successful implementation of DCTs depends on alignment between national infrastructure, regulatory frameworks and strategic priorities.

As DCTs become increasingly mainstream, continued dialogue between regulators, sponsors, investigators and patients will be essential to ensure that decentralised approaches deliver on their promise while maintaining the highest standards of participant safety and data integrity.