Leveraging Blockchain Technology for Informed Consent Process and Patient Engagement in a Clinical Trial Pilot

Objective: Despite the implementation of quality assurance procedures, current clinical trial management processes are time-consuming, costly, and often susceptible to error. This can result in limited trust, transparency, and process inefficiencies, without true patient empowerment. The objective of this study was to determine whether blockchain technology could enforce trust, transparency, and patient empowerment in the clinical trial data management process, while reducing trial cost. Design: In this proof of concept pilot, we deployed a Hyperledger Fabric-based blockchain system in an active clinical trial setting to assess the impact of blockchain technology on mean monitoring visit time and cost, non-compliances, and user experience. Using a parallel study design, we compared differences between blockchain technology and standard methodology. Results: A total of 12 trial participants, seven study coordinators and three clinical research associates across five sites participated in the pilot. Blockchain technology significantly reduces total mean monitoring visit time and cost versus standard trial management (475 to 7 min; P = 0.001; €722 to €10; P = 0.001 per participant/visit, respectively), while enhancing patient trust, transparency, and empowerment in 91, 82 and 63% of the patients, respectively. No difference in non-compliances as a marker of trial quality was detected. Conclusion: Blockchain technology holds promise to improve patient-centricity and to reduce trial cost compared to conventional clinical trial management. The ability of this technology to improve trial quality warrants further investigation.

A nationwide evaluation of the prevalence of human papillomavirus in Brazil (POP-Brazil study): protocol of data quality assurance and control (Preprint)

BACKGROUND The credibility of a study and its internal and external validity depend crucially on the quality of the data produced. Quality control aims to monitor sampling errors and measurements during the execution of a study and is based mainly on two pillars: planning and standardization of procedures. OBJECTIVE The present article aimed to describe the stages of quality control in the POP-Brazil study and to present an analysis of the quality indicators. METHODS Quality assurance and control included several phases and processes that were initiated with the planning of the study and continued through the development of the project; thus, all centers were trained in loco. RESULTS The data were through a structured questionnaire and collection of biological samples, both performed by more than 250 trained and certified health professionals. Furthermore, to correct possible inadequacies, all 119 centers (public health units) received at least one monitoring visit, which evaluated the professionals' performance and the process of completing the online data platform. The data were monitored daily and were audited through the double entry of data, performed by the central team. The reliability of data was analyzed through the test-retest method, comparing data from the online platform and a second application of the interview, and conducted through telephone, also by the central team. The agreement between the test and retest was considered good (kappa between 0.59 and 0.74). Large multicenter clinical trials are the basis of medical evidence-based and health-based prevention, so their design, logistics, and quality processes should always be carefully considered. CONCLUSIONS This article presents the processes and quality indicators in the POP-Brazil study that allow other studies to generate reliable data.

Continuous research monitoring improves the quality of research conduct and compliance among research trainees: internal evaluation of a monitoring programme

Background: Research site monitoring (RSM) is an effective way to ensure compliance with Good Clinical Practice (GCP). However, RSM is not offered to trainees (investigators) at African Institutions routinely. The Makerere University/Uganda Virus Research Institute Centre of Excellence in Infection and Immunity Research and Training (MUII-Plus) introduced internal monitoring to promote the quality of trainees’ research projects. Here, we share our monitoring model, experiences and achievements, and challenges encountered. Methods: We analysed investigators’ project reports from monitoring visits undertaken from April 2017 to December 2019. Monitors followed a standard checklist to review investigator site files and record forms, and toured site facilities. We planned four monitoring visits for each trainee: one at site initiation, two interim, and a closeout monitoring visit. A team of two monitors conducted the visits. Results: We monitored 25 out of the 26 research projects in progress between April 2017 and December 2019. Compliance with protocols, standard operating procedures, GCP, and GCLP improved with each monitoring visit. Median (IQR) compliance rate was 43% (31%, 44%) at site initiation visit for different monitoring items, 70% (54%, 90%) at the 1st interim monitoring visit, 100% (92%, 100%) at 2nd interim monitoring visit and all projects achieved 100% compliance at site closeout. All investigators had good work ethics and practice, and appropriate facilities. Initially, some investigators’ files lacked essential documents, and informed consent processes needed to be improved. We realized that non-compliant investigators had not received prior training in GCP/GCLP, so we offered them this training. Conclusions: Routine monitoring helps identify non-compliance early and improves the quality of research. We recommend continuous internal monitoring for all research studies. Investigators conducting research involving human subjects should receive GCP/GCLP training before commencing their projects. Institutional higher degrees and research ethics committees should enforce this as a requirement for project approvals.

The risk of sanctions following visits by monitoring bodies; a study conducted in Albania and Honduras

Introduction: Independent monitoring of places of detention is considered an effective way of preventing torture, but some reports have shown that detainees may face reprisals after engaging with monitors.This pilot study aims to further investigate the nature and the extent of such reprisals. Methods: A cross-sectional survey among male prisoners in 4 prisons in Albania and 4 in Honduras was carried out using an interviewer-administered, structured questionnaire and collecting additional narrative comments. Strict ethical guidelines were followed, and follow-up visits took place to detect any sanctions following participation in the study. Results: 170 detainees were invited to par- ticipate of whom 164 accepted. Most were aware of monitoring visits and found them helpful. More than one-third reported that au- thorities had made special arrangements like cleaning and painting prior to the monitoring visits, and 34% of participants in Albania and 12% in Honduras had felt pressured to act in a specific way towards the monitors. One- fifth had experienced sanctions after the last monitoring visit, most often threats and humiliations. During the follow-up visits, the interviewees reported no incidents following their participation in the study. Discussion: This pilot study has shown that it is possible to collect information about detainees’ experience with monitoring visits through interviews while they are still detained. The fact that reprisals are reported prior to and fol- lowing monitoring visits points to the need of improving monitoring methodology to further lower the risk. Further research is needed to better understand the dynamics of the sanctions taking place with the aim of reaching a deeper understanding of potential preventive measures.

Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis: a Single-Centre Experience

Background and Aims: Hereditary transthyretin (ATTRv) amyloidosis represents a diagnostic challenge considering the great variability in clinical presentation and multiorgan involvement. In this study we report the prevalence of gastrointestinal (GI) involvement of patients with hereditary ATTRv amyloidosis from one single center of Italy, a non-endemic area. Methods: We retrospectively analyzed a cohort of 39 patients with hereditary ATTRv amyloidosis followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy. All patients had a documented mutation in the gene encoding the thansthyretin. Neurological, cardiological and gastrointestinal manifestations were systematically collected at every monitoring visit. Results: 82% reported at least one GI symptom. Unintentional weight loss was the most frequently reported. Lower GI symptoms were more frequent than upper GI symptoms (66.7% vs. 35.9%, p=0.0122). The first GI symptom was always reported within 5 years since disease onset. Gastrointestinal symptoms were almost always present in patients with Val30Met mutation (93.8%, 15/16), and in more than half of the cases with Phe64Leu mutation (66.7%, 8/12). All cases with a non-Val30Met mutation disclosed almost all GI symptoms within 5 years since disease onset; conversely, patients with Val30Met mutation continued to develop further GI manifestations during the disease course. Conclusions: Prevalence of GI symptoms in our cohort was 82%, resulting in a higher prevalence than reported in the THAOS registry. Gastroenterologists, therefore, play an important role for the management of the disease, and their expertise should be valued for an effective multidisciplinary approach to this condition.

4500 Providing a System for Practical Monitoring Training for Clinical Trials within Academic Institutions

OBJECTIVES/GOALS: The goal was to understand the effectiveness of a novel clinical trial educational module and a corresponding initiative designed and disseminated by the Southern California Clinical and Translational Science Institute (SC-CTSI) to increase the quality of clinical trials conducted in academia. METHODS/STUDY POPULATION: The CRCs (Clinical Research Coordinators) for the initiative are asked to complete the online training. Possible study protocols are picked to be monitored by the CRCs. The monitor is instructed to study the protocol extensively and prepare for their monitoring visit. The trained monitor from the initiative then reaches out to the CRC of the study that is to be monitored and carries out the monitoring visit. Afterwards, the monitor sends initiative personnel the monitoring report, which is evaluated to see if the monitor checked everything they should have during the visit. The PI of the study is contacted with highlights from the monitoring report and improvements that they can make. RESULTS/ANTICIPATED RESULTS: The first study monitored was a site of a large NIH-sponsored study where the consent forms were signed electronically. It was found that the monitor could not access the consent forms. Therefore, the monitor could not do source data verification. The PI of the study said that they would be raising this issue with the NIH. During the monitoring visit of the second study chosen for the initiative, patient binders were specifically examined for informed consent and source documentation completeness. The charts of patients were also reviewed. The only deviation found was a missing signature in the Investigator Site File. For the last two studies, data will be reported. DISCUSSION/SIGNIFICANCE OF IMPACT: Monitors were not only able to monitor efficiently, but also able to point out deficiencies in the monitoring practices of large studies. This model could be expanded to other academic institutions to establish quality management systems to ensure data integrity and subject protection.