Bringing Trial Activities to Participants—The Trials@Home RADIAL Proof‐of‐Concept Trial Investigating Decentralization of Trials

Abstract

The interest in trials in which activities are being moved to the participants’ direct environment, that is, decentralized, has increased in recent years, but limited research has been conducted into the feasibility and acceptability of such approaches. The Trials@Home RADIAL proof‐of‐concept (PoC) trial aims to assess the scientific and operational feasibility and quality of a fully decentralized and hybrid trial approach compared to a conventional, site‐based approach. RADIAL is a three‐arm parallel‐group, open‐label, multi‐center low‐intervention phase IV trial conducted in people living with Type 2 diabetes mellitus in six European countries (DE, DK, ES, IT, PL, UK). The RADIAL trial compares three arms with the same clinical intervention (Insulin Glargine 300 U/mL) but differing degrees of decentralization (the methodological intervention), including online recruitment, remote consenting, remote visits, home‐shipment of Investigational Medicinal Product and study materials, home‐based biological sample collection, app‐reported events/ePROs, and home‐devices for data collection. Key Performance Indicators regarding recruitment, retention, diversity, site satisfaction, participant satisfaction, cost, safety oversight, treatment adherence, and data quality are the main outcomes of the trial. This paper discusses the set‐up of RADIAL, describing the design, endpoint selection, and decentralized elements evaluated, as well as discussing insight from RADIAL for future PoC trials. This is the introductory paper in a series of six papers in which we share the lessons learned during set‐up, regulatory submission, and conduct of RADIAL. By sharing these insights, we aim to support clinical trial designers, technology developers, and other stakeholders to successfully implement decentralized elements into clinical trials.

This trial was registered with identifier NCT05780151 in clinicaltrials.gov and under 2022‐500,449‐26‐00 in the Clinical Trials Information System (CTIS) clinical trial database.

TRIAL INNOVATION AND DECENTRALIZED APPROACHES

Randomized clinical trials are still considered the gold standard to provide valid evidence on the effects, benefits, and risks of healthcare interventions. ¹ , ² , ³ Traditionally, clinical trials have been conducted in hospitals or designated research sites, typically requiring participants to attend multiple in‐person study visits. However, it has become increasingly clear that this “conventional” clinical trial model faces difficulties including slow patient recruitment, low retention, high costs, large carbon footprint, selective participation not reflective of the population of interest, and a high burden on participants, site staff, and society. ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ These challenges put pressure not only on the efficiency of clinical trial conduct but also on the generalizability of the findings of clinical trials to clinical practice and the future users of the tested interventions. ⁷ , ¹¹ , ¹² , ¹³ Consequently, clinical trials are rapidly changing, enabled by significant advancements in reliable digital tools, data science, and clinical trial guidelines including the recently adopted ICH GCP E6(R3) which uses a proportionate risk‐based approach. ¹⁴ Numerous innovations in methods and operations are being developed and implemented, leveraging new technologies, analysis methods, and data sources. ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸

One such innovation is the relocation of some or all trial activities from clinical settings to the participants’ direct environment, referred to as decentralized clinical trial approaches (DCTs). ¹⁹ , ²⁰ DCTs leverage technology and/or innovative operational processes to facilitate various trial activities (e.g., informed consent, data collection) without requiring participants to travel to the clinical trial site. ¹⁹ Both in healthcare and clinical research, there is a growing body of evidence demonstrating the use of broadband internet, home computing, smartphones, wearable and non‐wearable digital technologies, medical devices, and biosensor technology to monitor the health of people from home. ²¹ , ²² , ²³ , ²⁴ , ²⁵

The interest in DCTs has increased in recent years ²⁶ with regulatory guidance, ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² stakeholder views ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ and best practices ²² , ³⁸ , ³⁹ being developed and shared. Most examples are of trials that use a combination of conventional site‐based activities and decentralized elements, often referred to as hybrid trials, ⁴⁰ , ⁴¹ , ⁴² with fewer examples of full DCTs, where participants never visit the clinical trial site. ³⁹ , ⁴² In addition, most trials with decentralized elements have been conducted in the USA rather than in a multi‐country setting in Europe, ³⁹ possibly due to the increased complexity of running a clinical trial in several countries, which may have different levels of acceptance of DCT elements. ⁴³ However, the recommendations and guidance recently issued by European regulatory authorities, which seek to harmonize the use of decentralized elements in clinical trials across the European Union ²⁷ , are expected to facilitate multi‐country DCTs in Europe. A non‐exhaustive overview of DCT elements is provided in Figure 1 .

Figure 1.

Non‐exhaustive overview of decentralized clinical trial elements.

ePRO, electronic Patient‐Reported Outcome; IMP, Investigational Medicinal Product.

DCTs hold the promise to improve trial access, speed up recruitment, enhance retention, and increase representativeness, while reducing the burden for participants and possibly sites. ²² , ²⁴ , ³⁸ , ⁴⁴ , ⁴⁵ , ⁴⁶ , ⁴⁷ A decentralized approach to trial recruitment, for example, by use of social media and liaising with advocacy groups, could enhance a trial’s visibility and accessibility for participants, independent of referrals from physicians. ⁴⁷ , ⁴⁸ Furthermore, the increased opportunities for active and passive collection of participant‐generated data can provide data that more closely reflects participants’ daily lives, norms, and values, and thereby provide better insight into disease progression and effectiveness of treatment strategies in the real world. ³³ , ³⁷ , ⁴⁹ , ⁵⁰ However, decentralization of trials may also bring challenges, such as possibly excluding people with limited digital skills from trial participation, adding operational complexity when increasing the number of vendors and regulatory restrictions. ²² , ²⁴ , ³⁸ , ⁴⁶ , ⁵¹ , ⁵²

Despite the steep increase in the use of decentralized elements during the COVID‐19 pandemic, ³⁸ , ⁵³ , ⁵⁴ to date, little is known about the effect of DCTs on Key Performance Indicators (KPIs), such as treatment adherence, safety oversight, and data quality. Furthermore, the potential benefits of DCTs regarding, for example, enrolment, retention, costs, participant satisfaction, site satisfaction, and diversity have not been proven, and insights into specific challenges that may occur in DCTs are limited. Also, there is no clear guidance on how to best operationalize the decentralization of clinical trial activities to meet ethical and regulatory requirements, improve trial efficiency, and decrease the burden for participants.

The Trials@Home RADIAL Proof‐of‐Concept (PoC) trial was designed and conducted to assess the feasibility and acceptability of DCTs. Such a PoC trial can provide the confidence to use a certain treatment, or in this case, trial approach, in future trials. ⁵⁵ The RADIAL trial compared three trial arms with the same clinical intervention but differing in their degree of decentralization (the methodological intervention). A wealth of insights has been gathered during set‐up, regulatory submission, and conduct of this trial. This is the introductory paper for a series of papers (see Box 1) in which we will share insights from the RADIAL PoC trial and relate them to other findings in this field, with the aim to support trial designers to more successfully select and implement decentralized elements into their trials. This paper will describe the design and set‐up of the RADIAL PoC trial and discuss the insights from RADIAL for future PoC trials.

Box 1. The RADIAL paper series.

This is a series of papers in which we share insights gathered during set‐up, regulatory submission, and conduct of the RADIAL proof‐of‐concept trial, the first clinical trial studying the feasibility and acceptability of decentralized trial approaches (DCTs). The papers will focus on:

1. Introduction into DCTs and the RADIAL trial.

2. Regulatory advice, interactions and approval.

3. Site selection and training for DCTs.

4. Recruiting and consenting decentralized trial participants.

5. Supply of investigational medicinal product and study materials to decentralized trial participants.

6. Technological solutions for DCTS.

For each of these topics, we discuss why the topic is important in DCTs, elaborate on how we set this up in the RADIAL trial, share our experiences and learnings, contrasted against what is known from the literature, and provide recommendations for future trials.

RADIAL, A PROOF‐OF‐CONCEPT TRIAL

The RADIAL (Remote And Decentralized Innovative Approach to clinical triaLs) trial is a pan‐European PoC trial that aims to assess the scientific and operational feasibility and quality of a fully decentralized and hybrid trial approach compared to a conventional, investigational site‐based approach. RADIAL is a three‐arm parallel‐group, open‐label, multi‐center low‐intervention phase IV trial conducted in six countries in Europe: Denmark, Germany, Italy, Poland, Spain, and the United Kingdom. People living with Type 2 diabetes mellitus (T2DM) with glycated hemoglobin (HbA1c) between 7% and 10% and treated with basal insulin started using Investigational Medicinal Product (IMP) Insulin Glargine 300 U/mL instead of the basal insulin they were using before the trial. The study consisted of two parallel parts (part A and part B) with three different arms. Part A used site‐based recruitment, and participants were randomized 1:1 to either the conventional arm or the hybrid arm. Part B was a fully decentralized arm utilizing remote recruitment methods.

The primary study objective of the RADIAL trial was to assess potential benefits of a DCT approach regarding participant recruitment, retention, diversity, site satisfaction, participant satisfaction, and cost, in addition to determining the acceptability of a DCT approach by measuring variables related to safety oversight, treatment adherence, and data quality (missing data and query rate) within the arms. KPIs were defined to measure these aspects of benefits and acceptability and served as the main outcomes of the trial. The secondary study objective was to determine whether the efficacy of Insulin Glargine 300 U/ml treatment remained within the accepted range within the arms with different degrees of decentralization.

CO‐CREATION WITH STAKEHOLDERS AND RECEPTION OF THE RADIAL TRIAL

People with lived experience played a pivotal role in shaping the RADIAL clinical trial protocol and the accompanying informed consent information through active and ongoing participation in the Trials@Home Patient Expert Panel (PEP), led by the International Diabetes Federation Europe (IDFE). Their contributions included insights into the lived experience of T2DM, helping researchers understand what motivates trial participation and identifying potential barriers to recruitment, adherence, and retention. PEP members confirmed the relevance of the study outcomes and influenced the choice of digital technologies and operationalization of DCT elements, emphasizing accessibility and user‐friendliness. In addition, the Trials@Home External Stakeholder Panel (ESP) was consulted on the trial protocol. The ESP consisted of about 20 members, representing patient organizations, healthcare providers, clinical researchers, pharma, CRO, MedTech, regulators, HTA bodies, payers, and ethical and legal experts.

The RADIAL trial was submitted under the Clinical Trial Regulation 536/2014, and the Medicines for Human Use (Clinical Trials) Regulations 2004, in the EU and UK, respectively. In preparation for the RADIAL trial—including selecting countries, operational approaches as well as regulatory submission—multiple routes of stakeholder advice were used. These included both informal engagement with regulators, ethical committees, and HTA bodies, ³³ , ³⁵ , ³⁷ and formal consultation routes, including the European Medicines Agency’s Innovation Task Force and national Scientific Advice procedure, as further described in the second paper in this series. ⁵⁶

SCIENTIFIC RATIONALE AND RADIAL DESIGN CHOICES

The methodological intervention

As described above the RADIAL trial was designed to compare the scientific and operational quality of a fully decentralized trial and a hybrid trial against a conventional site‐based clinical trial and to evaluate their feasibility. To this end all three trial arms received the same clinical intervention but differed in their degree of decentralization, that is, the methodological intervention. The RADIAL trial consisted of two parts. Part A included the conventional and the hybrid arm. The conventional arm was modeled after a previous clinical trial with a similar indication and intervention and aimed to reflect the current state‐of‐the art in conventional clinical trial conduct. The hybrid arm incorporated both conventional trial elements, such as site‐based recruitment and screening visits, and decentralized trial elements, such as a remote data collection and follow‐up. Part B consisted of the remote arm, which was fully decentralized, including remote recruitment and consenting; participants in this arm never came to a site but were managed remotely throughout the trial. See Figure 2 for an overview of the three study arms and the decentralized elements used. These elements are described in more detail under “Schedule of assessments and decentralized elements.”

Figure 2.

Design of the RADIAL PoC trial. DtP, Direct‐to‐Participant; ePRO, electronic Patient‐Reported Outcome; FU, follow‐up; HbA1C, glycated hemoglobin; IMP, Investigational Medicinal Product.

Three arms in two study parts

The rationale for having three arms in two separate but parallel Parts A and B was to allow for the testing of the fully decentralized model. That is, if participants were randomized across all three arms, all possible participants would need to be willing and able to travel to site as well as participate in a fully remote fashion since they could be allocated to any arm. This requirement would most likely preclude the participation of people who could join a fully decentralized and possibly a hybrid trial but could not come to site on a regular basis because they live too far away from a site. Consequently, randomization across all three arms would mean that neither the conventional nor the decentralized arm would truly represent the model it stands for, and recruitment, diversity, and possibly also some of the other KPIs under study could not be assessed correctly for each arm. For the same reason, and to prevent decreasing contrast between the arms, it was also decided not to allow flexibility in the arms regarding the location of activities, albeit in itself an interesting concept for tailoring toward participant preferences for trial delivery. As such, the design as described above was chosen for the RADIAL trial. The randomization in Part A ensured looking at the same population of participants for both the conventional and hybrid arm. The remote arm in a separate Part B allowed for investigating a fully decentralized approach including country‐wide online recruitment. As a result, the study populations in Part A and Part B may differ. This variability should be considered when comparing outcomes between the arms.

Choice of therapeutic area and clinical intervention

The consortium evaluated several potential therapeutic areas for the RADIAL trial, with a view to possible impact on health care, feasibility, and generalizability to other disease areas. T2DM was chosen as the therapeutic area for the study because it is a chronic disease with high disease burden and prevalence in a broad patient population, aiding the extrapolation of the findings to other disease areas and populations. It is a condition that is characterized by a significant patient burden, with a large part of treatment being routine self‐monitoring. Moreover, there are accepted clinical outcomes for T2DM that can be self‐measured, and there is a variety of technologies available for remote monitoring and oversight which could be used in the hybrid and remote arm. The rationale for choosing Insulin Glargine 300 U/mL as the study medicine was threefold. First, Insulin Glargine 300 U/mL is a medicine that is easily administered at home, with safety that can be monitored remotely and a low‐risk profile. Second, it provides relevant data on the feasibility of a cold chain in Direct‐to‐Participant (DtP) IMP shipments for future decentralized trials. Finally, people living with T2DM with an HbA1c between 7% and 10% on current glucose‐lowering therapy may potentially benefit from switching to Insulin Glargine 300 U/mL.

Choice of countries

The RADIAL trial was conducted in six European countries. The selection followed a structured, multi‐step process designed to ensure a broad representation across Europe, diverse healthcare systems, legal and regulatory environments, and operational feasibility in terms of recruitment and startup timelines. Initially, 21 countries were considered, leveraging insights from the consortium members, the regulatory mapping carried out for 11 of these countries in the Trials@Home project ⁵⁷ and recruitment potential. This list was subsequently refined by applying knock‐out criteria regarding startup timelines and acceptability of decentralized trial elements (e.g., electronic consent and home delivery of IMP). A detailed feasibility assessment was conducted at the site level in 17 countries to establish the final country selection for the study, which is described in more detail in paper three of this series. ⁵⁸

Definition and selection of KPIs

As the RADIAL trial aimed to compare three approaches (fully decentralized, hybrid, and conventional) for scientific and operational quality, the outcomes of interest were KPIs rather than clinical endpoints. Clinical endpoints were included as secondary endpoints. Using a modified RAND/UCLA Appropriateness Method (RAM) Delphi study ⁵⁹ with a panel of 16 experts, 10 main and 12 secondary KPIs to be measured in the RADIAL trial were identified. The Delphi study consisted of several rounds: (i) Identification of KPIs of interest for the trial, (ii) Deduction of KPIs through review for uniqueness and measurability, (iii) Prioritization of KPIs through ranking procedure, (iv) Classification of KPIs through operationalization and measurement effort and (v) Selection of final list of KPIs. The 10 main KPIs are shown in Table 1, including a description of how these were operationalized and which research question they addressed. The KPI for enrollment is reflected upon in paper 4 of this series. ⁶⁰ The other KPI findings are not described in this RADIAL series, which focuses on operational learnings. However, all KPI analysis will be made available through the summary of the clinical study report, published on Clinical Trials Information System (CTIS), and in further scientific publications on the RADIAL trial.

Table 1.

List of Key Performance Indicators (KPIs) defined for the RADIAL Proof‐of‐Concept trial

KPI	Endpoint	Research questions
Objective related to KPI
Primary study objective 1: To assess potential benefits of a DCT approach on participant recruitment, retention, diversity, site and participant satisfaction, and cost
Enrolment rates To compare the enrolment rates and timelines between Part A and Part B	Time to enrolment from site activation until last participant enrolled	Is there a difference in enrolment rate using a decentralized recruitment method compared to a site‐based recruitment method?
Retention rates To compare the retention rate and time on study between the arms	Proportion of participants completing the study period	Is there a difference in retention rate in a conventional study design compared to both a hybrid and a decentralized study design?
Diversity To compare diversity in the participant population between Part A and Part B based on set variables, such as age, ethnicity, and socioeconomic status	Various diversity aspects such as race, ethnicity, socioeconomic status, digital literacy, distance to health care professional, mobility	Is there a difference in diversity in decentralized‐recruited compared to site‐based recruited participant populations?
Participant satisfaction To compare the participant satisfaction between the arms and identify challenges and opportunities for trial execution from a participant perspective	Participant satisfaction measured using an adapted version of the TransCelerate Study Participant Feedback Questionnaire (SPFQ) just after Visit 2 (baseline), Visit 6 and Visit 9 (End Of Treatment, EOT)	Are there differences in participant satisfaction in a conventional study design compared to both a hybrid and a decentralized study design?
Site staff satisfaction To compare the satisfaction of site staff between Part A and Part B and identify challenges and opportunities for trial execution from a site perspective	Site staff satisfaction measured using a questionnaire (after site initiation visit [SIV]), after three enrolled participants, after three participants completed Week 12 and after last patient last visit (LPLV)	Are there differences in site staff satisfaction in a decentralized operational model compared to a site‐based operational model?
Study Cost To compare study costs between the arms from a modified societal perspective	Absolute cost per participant using a combination of prospective and retrospective measurements	Are there differences in study costs for a conventional study design compared to both a hybrid and a decentralized study design?

Primary study objective 2: To determine acceptability of a DCT approach by measuring variables related to safety oversight, treatment adherence and data quality (missing data and query rate) within arms that have a different degree of decentralization
Time of Adverse Event/Serious Adverse Event (AE/SAE) occurrence to collection To investigate the AE/SAE time from occurrence to data collection in the arms	Time from event occurrence to collection AE/SAE in the study app or eCRF, whichever is applicable	Is the time from occurrence of an AE/SAE to the collection of AE/SAE acceptable in each trial arm?
Treatment Adherence To investigate the treatment adherence in the arms	Adherence to the daily insulin injection by means of analysis in percentage of days of documented intake until participant’s EOT	Is the treatment adherence acceptable in each trial arm?
Missing data To investigate the proportion of missing data and reasons for missing data in the arms	Proportion of missing data on different critical data points (Hb1Ac, Fasting Glucose, Participant satisfaction questionnaire)	Is the proportion of missing data acceptable in each trial arm?
Query rate To investigate the query rate in the arms	Number of queries (both manual and automatic) per participant per arm	Is the query rate acceptable in each trial arm?

Schedule of assessments and decentralized elements

As is shown in Figure 2 , the frequency and timing of visits/reporting timepoints and collection of information during trial conduct were similar across arms, but the degree of decentralization varied per arm (e.g., which data collected via eDiary and devices, method of drug dispensation). Participants in the conventional arm had in‐person study visits at the clinical site during screening, baseline (Week 0), Week 12, and End Of Treatment (EOT), and received phone calls to collect data at scheduled timepoints. Participants in the hybrid arm had in‐person study visits at the clinical site during screening, at baseline (Week 0), and at EOT. A home nurse visit was scheduled for Week 12. In addition, at scheduled reporting timepoints, participants received a notification via the RADIAL trial app to ask them to confirm that the data they reported in the app was complete and accurate. Participants in the remote arm had telemedicine contacts during screening, at baseline (Week 0), Week 12, and EOT. In addition, at scheduled reporting timepoints, participants received a notification via the RADIAL trial app to ask them to confirm that the data they reported in the app was complete and accurate. In addition to this, in all three arms, data was collected remotely in between visits, phone calls, and/or reporting timepoints by utilizing digital tools; see Supplement 1 for the full schedule of activities of the three arms of the RADIAL trial. In total, seven decentralized elements were implemented in the RADIAL trial; see also Figure 3 : (i) online recruitment and prescreening in Part B only; (ii) remote consenting in Part B only; (iii) remote trial visits as telemedicine visits in Part B and as home nurse visits in the hybrid arm of Part A; (iv) DtP shipment of IMP and study materials in Part B and hybrid arm of Part A; (v) at‐home collection of biological samples, that is, capillary blood samples for HbA1C measurement, collected by the participant in Part B and by a home nurse in the hybrid arm of Part A; (vi) self‐reporting of events and ePROs through a study app in Part B and hybrid arm of Part A; (vii) data collection using sensors and wearables, that is, monitoring of treatment adherence through a smart insulin injector cap and glucose through a connected glucometer, synchronizing the data to the study app in Part B and the hybrid arm of Part A.

Figure 3.

Decentralized elements used in the RADIAL proof‐of‐concept trial. ePRO, electronic Patient‐Reported Outcome; IMP, Investigational Medicinal Product.

INSIGHT FROM RADIAL FOR FUTURE POC TRIALS

In this paper, we have described the development and set‐up of the RADIAL PoC trial. The insights generated by the trial regarding DCTs will be discussed in the other papers of this series (see Box 1). ⁵⁶ , ⁵⁸ , ⁶⁰ , ⁶¹ , ⁶² Some overarching insights related to the PoC nature of the trial will be shared and discussed here.

The Oxford Specialist Handbook defines a PoC study as a study which is designed to deliver evidence of efficacy in a small number of selected patients. It is designed to provide the confidence to progress to later studies, with the minimal possible investment, and with results delivered in the shortest possible time. ⁵⁵ A methodological PoC trial such as RADIAL has the same aim; however, it focuses not on the decision to progress a clinical intervention to later studies, but rather on whether a methodological or operational approach can be safely and effectively used in future trials. The Trials@Home experience is that performing the RADIAL PoC trial not only provided knowledge on the scientific and operational quality of the decentralization of clinical trials, but through the interactions with all stakeholders in the field, provided many additional insights on perceptions and acceptability of DCTs, as well as on operationalization of DCT elements. By setting up and conducting the RADIAL trial within a multi‐stakeholder consortium and engaging actively with the broader clinical trial community, we initiated discussions and developments in the field even before the final trial results have been obtained and shared. ⁶³ , ⁶⁴

To make sure that the RADIAL PoC trial provided insights relevant for future (drug) trials, RADIAL was designed as an interventional study, including an IMP. This set‐up was chosen so that the trial had to go through the regulatory approval system for drug trials, which is currently one of the most highly regulated sectors in the world. By setting up a PoC trial in such a way, opportunities are created for direct interactions with regulators and open discussions on the regulatory requirements and how to move the field forward. Details on these regulatory interactions and insights can be found in paper 2 of this series. ⁵⁶

Another learning from RADIAL was that it is of utmost importance for a PoC trial to address a research question relevant to possible participants and health care providers. Despite early engagement of people with lived experience and other stakeholders, the RADIAL PoC trial was perceived by some sites to be of limited interest to people living with T2DM, adversely affecting recruitment for the trial. The methodological research question regarding decentralization, which could lead to less burdensome future trials, was not considered compelling enough for people living with T2DM by these sites. This finding is supported by research into best practices for DCTs. ³⁹ A more detailed reflection on recruitment and consenting within RADIAL can be found in paper four of this series. ⁶⁰

A major advantage of a PoC trial over, for example, a paper exercise on the acceptability of a certain trial design is that the operational set‐up and execution by sites and participants provide additional insights on, in this case, effective use of decentralized elements. For example, on how to set‐up DtP IMP shipment, aligned with country and local regulations in each country, which is further detailed in paper five of the series. ⁶¹ And on how to train and support sites regarding DCT elements and technologies, as can be read in papers three and six of this series. ⁵⁸ , ⁶² On top of these insights, conducting a PoC trial may also lead to capacity building. For RADIAL, a total of 38 sites in six countries were trained on and supported in the use of different DCT elements in trials.

In the subsequent manuscripts of this series, insights and recommendations will be provided based on the experience gathered with RADIAL. These insights can be used when deciding whether or not to include decentralized activities in a trial. As such, RADIAL will meet the aim of a PoC trial to provide insights into whether a methodological or operational approach can be safely and effectively used in future trials; although a careful translation of our findings to the trial in question is always required. What are the possible consequences on the data collected, the investigator oversight, as well as participant and site burden of a decentralized and a site‐based approach? What is the best way to operationalize a certain decentralized activity, for example, regarding remote recruitment options or processes for at‐home collection of biological samples? With this series of papers, we hope to provide tools for trial designers on how and when to more successfully implement decentralized elements into their future trials.

FUNDING

The Trials@Home project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 831458. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA (www.imi.europa.eu).

CONFLICT OF INTEREST

MH and LR are employees of Sanofi and hold shares in this company. ISM reports institutional research grants from British Heart Foundation, Menarini, EMA, Sanofi, HDR UK, NIHR HTA, AstraZeneca, Wellcome Trust, NovoNordisk, TICR, IMI, IHI (Innovate Guarantee), University of Oxford and University of Bordeaux; institutional consultancy income from AstraZeneca; personal consultancy/honorarium income from AstraZeneca, Amgen, Amarin, Novartis, and Novo Nordisk; support to attend conferences from Novartis; membership of DMC of WAVE, CARE‐UK, and AFFECT; vice‐chairmanship of TSC of ASCEND PLUS; vice‐chairmanship of Scottish Heart and Arterial Risk Prevention (SHARP) society. SB work for IDF Europe, a non‐profit organization focused on diabetes advocacy, policy, and education. As part of this role, SB has participated in activities and received support (e.g., grants, speaking engagements, or collaborations) from various stakeholders in the diabetes field, including pharmaceutical and MedTech companies. All other authors declared no competing interests for this work.

DISCLAIMER

The research leading to these results was conducted as part of the Trials@Home consortium. This paper only reflects the personal view of the stated authors and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein.

Supporting information

Data S1

Data S2