Ethics review of digital health research: Rethinking rights of participants

The primary responsibility of the ethics committee (EC) is to ensure the protection of the rights, safety, and well-being of research participants.1 Several guidelines – Indian Council of Medical Research (ICMR), International Council for Harmonisation, and Indian Good Clinical Practice, and World Health Organization have provided detailed guidance for the operational aspects of EC functioning. However, two studies published in this issue of the journal highlight concerns in ethics review of clinical research.2,3 In a scoping review, Kalel et al.2 have reported significant gaps in the competence of EC members and structural, functional, and procedural weaknesses in ECs.2 In a survey, Marathe et al. found that EC members were aware of the need for assessment of risks and benefits of clinical research studies.3 However, none of the survey respondent EC members, had received specific training to carry out risk–benefit assessment.3 In contrast, a study conducted by Rao et al. revealed how the use of digital health technology (DHT) in drafting informed consent documents (ICDs) can create ethical issues. They found that generative artificial intelligence (AI) tools can emulate the structural and linguistic characteristics of ICD templates with moderate ethical and procedural adequacy. However, they frequently omit context-specific ethical details.4 The surveys raise apprehensions about the current environment for adequacy of ethical review of clinical research, while the AI study highlights the novel challenges for ethics review of DHT research (DHTR). DHT utilizes computing platforms, connectivity, software, and/or sensors for health care and related domains.5 DHTs are now being used in health care to support data collection, increase patient centricity, and facilitate data curation and trial management.6 Some examples include telehealth platforms, smartphone apps, wearable devices, trackers, biosensors, AI-driven tools, and remote patient monitoring devices. DHTs, e.g., electronic health records, electronic case record form, patient-reported outcomes, electronic consent, and video consent, have also become a important tools for collecting participant data. DHTR is new innovative approach to recruit participants from social media, use digitally collected data for developing clinical decision support software, for assessing effectiveness or safety of therapies by monitoring of patient’s clinical condition, for building and training AI models to monitor disease progression, testing the effectiveness of AI model to detect tumors using computed tomography images, and for conducting virtual or digital trials. Digitally collected data have the advantages of easier access, better data quality, and rapid data extraction and analysis compared to data collected on paper. However, widespread use of DHTs and AI in clinical research have brought to the fore a wide variety of ethical issues such as autonomy, accountability and liability, accessibility and utility for participants, collaboration and conflict-of-interest, data access and collection, data storage and security, data protection, equity and inclusiveness, nondiscrimination, privacy, safety and risk minimization, security, transparency, trustworthiness, and validity of technology.1,6-12 ECs should consider these issues while reviewing clinical research employing DHT. EC should assess whether the use of DHT in clinical research is a medical device. If the purpose of research is to evaluate DHT for diagnosis, cure, mitigation, treatment, or prevention of disease, it would be considered a medical device by regulatory agencies. Besides, software or apps used in DHT are also considered a medical device – Software as Medical Device. EC should review how the rights of participants included in data protection regulations are protected.8-10 These rights include the right of access, information, rectification, correction, updating, restricting processing, and erasure; right to data portability, option to nominate a representative; and rights in relation to automated decision making and profiling. The protocol should specifically include all details of DHT – selection, rationale for use in clinical study, design and operation, technical specifications, validation, and usability evaluations.13 In addition, it should describe the education, language, age, and health/physical condition of study population. There should be a description of how educationally disadvantaged participants with low digital literacy and low technical aptitude would be trained if included in the study. It should also highlight clinical, technical, and privacy-related risks, and critical aspects related to data, e.g., anonymization, sharing, management, data security, and data storage.7,11,12 The ICD should include a description and rationale of selecting DHT and primary and secondary objectives of DHTR. The participant should be informed about how, when, and under what conditions DHTs will be used and given explanation of confidential and identifiable data. ICD should explain participants’ rights of data protection and ownership. The processes for collecting, securely storing, sharing, and transferring data to other stakeholders and likelihood of commercial use of data should be explicitly described in ICD. The participant should know about the limitations of data removal if he/she withdraws from the study. The participants should be made aware of potential risks such as privacy and security risks, data reidentification, data breach, physical injury, technology malfunction, and psychological discomfort of DHTR conduct. They should be informed about compensation available if they suffer from a serious adverse event during the conduct of DHTR. Only direct benefits related to use of DHTs should be highlighted. The participants should be told about any costs of smartphone service/Internet connection that they have to bear during the conduct of research.1,7,14 Review of clinical trial agreement (CTA) is of utmost importance as the outcome of DHT use in research is often commercial. CTA between the sponsor–DHT developer and the investigator–researcher should describe responsibilities of the sponsor or tech developer to comply with trial regulations and data protection rules; of validation, quality, risk management of DHT; and of data protection, security, and data anonymization; of training of the site team in the use of DHT; and ensuring vendor oversight. CTA should detail the sponsor’s liability for indemnity and compensation. CTA should also describe the responsibilities of investigator–researcher to adhere to the rules and regulations of clinical trial conduct, protection and security of data, obtaining informed consent, ensuring participant safety, and training of participants in the use of DHT. If the DHT is developed by the investigator–researcher, he/she would be responsible as the sponsor. The agreement should cover delineation of data ownership, data storage location and transfer, financial obligations and conflict of interest, ownership of intellectual property rights, and policy for publications coming out of DHTR. ECs face the novel challenge of unanticipated ethical concerns while reviewing clinical research projects using DHT. ECs should include DHT experts and legal experts with information technology experiences in the committee, get trained in technical and ethical aspects of DHT, adapt the ICMR-recommended ethics checklist of AI for biomedical research and health care7 for review of DHTR, and create appropriate standard operating procedures. Rethinking the rights of participants and risks of DHTR to become competent in appraisal of DHTR is an urgent imperative for ECs to ensure competent ethical oversight in the digital age!