Co-author: Neha Singh
Decentralized clinical trials (DCTs) involve minimum or almost no ‘in-person interactions’ between the patient and the site personnel including the investigator. The virtual study ‘direct-to-patient’ model is the core theme around which DCTs revolve. They are completely site less, thus the data is collected remotely through connected devices, telemedicine, and mobile healthcare providers. Unlike traditional trials, in DCTs, there will be non-laborious data cleaning steps facilitated by MDM activities.
Evolution of Clinical Trials
Clinical trials evolved slowly in the past few years and traversed an interesting journey starting from site-based traditional trials to site-less decentralized trials.
It all started with the first double-blinded controlled trial for the common cold in 1943. These traditional trials are completely carried out at the trial sites and require patients to visit the trial sites multiple times during a study. Clinical operations and data management are done strictly using legacy systems like CTMS, EDC, and CDMS, where clinical data management was carried out in a manner quite different from today. The use of RWE/RWD is a complete miss in traditional trials.
Virtual trials emerged as a trend in the last few years in which all visits are e-visits. Health apps, mHealth, eSource, and connected devices such as wearables are the main tools for remote data collection.
While going through the website clinicaltrials.gov, we found that most virtual trials had predefined study sites, and data was collected through virtual/e-visits. This indicates overlap of virtual and traditional trials which may be defined as hybrid clinical trials.
Hybrid trials are traditional site-based and may also have data coming from a source that can be labeled as site less. In hybrid trials, some of the activities might be site less and can be done remotely such as patient recruitment, seeking patient consent, monitoring, and QoL questionnaire, etc. While some other activities, such as screening visit and last visit as per study protocol, might be site-based where initial/last vital stats and medical tests can be done at the site. Clinical data management is carried out using traditional EDC/CDMS applications and some of the information will flow into the database using RWD/RWE methodology.
Decentralized clinical trials are the future of clinical research. These trials are completely site-less and visit-less. All activities starting from the trial recruitment to patient exit is preferably done remotely, at the comfort of the patient’s home. This also means that RWD/RWE is the key to derive results. The most ideal candidate for this type of studies are late phase/PMS trials.
Sometimes, there may be a partial implementation of DCT wherein some of the diagnostic tests such as MRI, CT Scan etc. are being carried out at the site or central labs while for others, such as checking of glucose level or basic Pulmonary Function Tests (PFTs), data might be collected from patient’s pool of information.
Benefits of DCTs
A few days back, I was discussing clinical trials in the current COVID-19 situation, with a fellow data scientist. Per the present-day scenario, we don’t have any dedicated vaccine to put an end to this outbreak. Clinical trials for possible COVID-19 vaccines are the need of an hour to cure this epidemic. Trial recruitment and execution including various tests to be done is a challenging task, as everyone is bound to stay at their homes.
In this scenario, decentralized clinical trials are the best option available with researchers for late phase studies. With the help of social media listening and other similar methods, recruitment can be done. Patient consent can be taken using EICF followed by remote screening and enrollment instead of paper-based approach taken at the sites. Using technologies based on biosensor enabled data collection devices, medical tests can be managed without the requirement of any local labs. Decentralized clinical trial will surely expedite the study process to gauge primary and secondary endpoints, while addressing vaccine efficacy in terms of seroconversion and seroprotection.
Safety of clinical data management will also be straightforward as information can flow well within stipulated timelines as required by authorities. Thus, DCT offers convenience, compliance, and ease while also helping in prevention of further spread of disease by maintaining social distancing between already stressed individuals in these difficult times.
Impact of Regulations
FDA says that DCTs will help make trials efficient by reducing the administrative tasks of site staff with no compromise on the data quality and integrity. The regulatory agencies have increased their focus on data privacy, processing, and technology. In DCTs, data is collected securely, and data privacy is ensured
Another major factor of significance in trial design is patient diversity. Per FDA guidelines, trial participants must be diversified to have an effective trial outcome. Trial recruitment should also focus on the most abandoned population like the elderly, women, minorities, etc.
Per various studies, the dropout rate of patients in trials is usually very high. Long-distance travelling to sites, family/work responsibilities of the potential patient, and health issues may reduce patient’s visits to the study site or may lead to mid-way drop from the trial. Thus, DCTs help to ensure regulatory compliance in accordance with study protocol.
Data Quality in Decentralized Clinical Trials
One parameter that is most important for the sponsors and CROs is the data quality along with better data processing and reduced costs, which is a challenge in most of the traditional trials.
DCT comes as a savior as there is no manual data processing at the sites or at the sponsor’s end. As the health-related data is collected directly from digital devices; it is free from errors, complete and within range. Duplicity, redundancy, and missing data points are concerns of the past.
HCL Platform and Data Flow
HCL’s DCT model provides a clinical platform which is a combination of service, technology, regulatory compliance, and operational aspects. This solution is also capable of managing the pharmacovigilance data along with clinical endpoints.
Decentralized clinical trials make use of modern-day advanced technologies for data transmission such as artificial intelligence (AI), natural language processing (NLP), robotics, machine learning (ML), and blockchain.
These technologies have transformed clinical trials by extracting only relevant data from the pool of voluminous data received from multiple connected device end points, generated daily. This not only reduces data transmission time but also guarantees a consistent gold standard in terms of better data quality.
Telemedicine plays a vital role in connecting the patient with medical care at the comfort of their home. The clinicians and the patient can have interactions via video calls for various health/ medicine related issues. Training to comply with study regimen can be imparted through gazettes based on virtual reality.
Health apps and connected devices are also used to collect and manage patient-reported outcomes. These devices and apps are connected to database servers of the sponsor/CRO and sync the data time to time.
Hundreds of end points are collected each day for each patient from the continuous inflow of data. The value of the most apt parameters per the prespecified criteria in the protocol is automatically sent to the server.
The life sciences industry intends to make clinical trials more patient-centric. Sponsors should realize the long-term benefits of patient-centric trials and reduce the burden on the patient. DCTs offer a paradigm shift of modern-day trials to focusing more on ‘what the patients want’ instead of ‘what the sponsors want’.
For sponsors, decentralized trials will also eliminate efforts for data entry, processing, and monitoring. DCTs will provide an accurate, time- and cost-effective solution in comparison to the traditional clinical trials.
List of Acronyms Not Covered in the Blog Post
- CDMS: Clinical Data Management System
- COVID-19: Coronavirus Disease 2019
- CRO: Contract Research Organization
- CTMS: Clinical Trial Management System
- CT-Scan: Computed Tomography Scan
- EDC: Electronic Data Capture
- eICF: Electronic Informed Consent Form
- FDA: Food Drug Administration
- MDM: Master Data Management
- MRI: Magnetic Resonance Imaging
- PMS: Post Marketing Surveillance
- QoL: Quality of Life
- RWD: Real Word Data
- RWE: Real World Evidence
- Tele-med: Telemedicine
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- ‘Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry’, FDA-2019-D-1264, Jun 2019,
- Koester A , ‘How one pharmaceutical company is reinventing the clinical trial’, Sep 2018,