While the principle of participant consent is better appreciated in clinical research today than in previous decades, the opportunities for error remain considerable. However, a combination of digital technologies and effective protocols guard against these, explains Montserrat Valdes, who provides a US perspective.
The Tuskegee Study of Untreated Syphilis in African American males highlighted not only the importance but also the risks associated with the lack of informed consent in clinical research . In 1932, the United States Public Health Service (USPHS) and the Tuskegee Institute rolled out a study to investigate the natural course of syphilis. The participants of this study were 600 Black men, 399 with syphilis and 201 without the disease. The researchers did not collect informed consent and, in fact, told the participants that they were being treated for “bad blood”. In exchange for participation in the study, the participants received free medical examinations, meals and burial insurance.
By the mid-1940s, it was clear that penicillin was effective for treating syphilis. However, the 399 syphilis patients in the Tuskegee study were not offered the treatment.
The study was ceased in 1972 due to a recommendation from an Ad Hoc Advisory Panel convened by the Assistant Secretary for Health and Scientific Affairs, following the publication of the story by the Associated Press. In addition, the Tuskegee Health Benefit Program (THBP) was set up to provide medical care to the participants, their spouses and children. A class-action lawsuit was filed on behalf of the participants that resulted in a US$10 million out-of-court settlement. This case underscores the importance of informed consent in clinical research.
What is informed consent?
In simple terms, informed consent implies that a research participant has been given all the information pertaining to a study, including possible benefits, risks and adverse consequences, and in turn, they have countersigned that they accept to proceed with the study having full knowledge.
Applicable regulations for informed consent
In the USA, applicable regulations for informed consent include the Common Rule governed by the Department of Health and Human Services (DHHS) and the US Food and Drug Administration (FDA) regulations at 45 CFR 46.116 and 21 CFR 50.25.
For studies conducted outside the US, the International Council of Harmonization’s Good Clinical Practice (ICH GCP) guidelines are applicable . Fortunately, most elements of ICH-GCP are aligned with the US regulatory requirements. Also, note that it is not necessary to include regulatory requirements that do not apply to a given study. For example, it may not be necessary to include Common Rule elements in a study regulated by the FDA unless the study has been funded by the DHHS. The following are the regulations that apply to informed consent:
- Common Rule
- 21 CFR Part 50 & 56
- 45 CFR Part 46
- ICH GCP E6 (4.8.10)
- State laws
- Institutional policies
How to maximise compliance and minimise risk – digital technologies
Population-scale research programmes such as the NIH All of Us and the National Covid Cohort Collaborative have brought to light the need for digitised consent management, aka eConsent . Digitised consent requires bidirectional and multimodal interactions between the trial sponsor/ researcher and the participant to establish trust and foster long-term relationships. The participants should be able to ask questions and get feedback in real-time to facilitate the process. This preempts the need for advanced platform technology in the management of eConsent.
Cloud-based and human-centric technology platforms are ideally designed to provide real-time and secure collaboration between clinical trial stakeholders . One example of such a platform is laboratory software for clinical research, also known as Laboratory Information Management System (LIMS), hosted in the Cloud. This strengthens trust between the research team and trial participants, boosts productivity and brings transparency to clinical research. Such a platform tracks the journey from how potential participants are selected, educated and if and how they offer consent. The consent is managed electronically, and how the participants are screened and enrolled in the study is also tracked via the LIMS platform to ensure compliance with all regulatory requirements. Automation through LIMS enables researchers to keep up with compliance despite the magnitude of the project, stakeholders involved or time constraints.
How does Cloud-based laboratory software for clinical research support eConsent management?
Laboratory software for clinical research enabled the automation of those processes, including consent management. A Cloudhosted LIMS streamlines workflows and allows stakeholders to access the study data remotely from any internet-ready device at any time . This reduces the logistical burden and offers flexibility to enable more participants to offer consent and take part in clinical research, also minimising the study dropout rate, which is a significant burden in clinical research.
Informed consent – the foundation of ethical clinical research
Informed consent is crucial for conducting clinical research ethically. As seen in the Tuskegee study, failure to obtain informed consent is unethical and may result in adverse financial and reputational ramifications.
The DHHS, FDA and ICH provide regulations for the management of informed consent. Individual countries and states may have additional regulations.
Digitisation of consent management allows trial sponsors to execute larger or time-bound trials. Laboratory software for clinical research enables clinical trials to automate and manage digitised consents while maximising efficiency and output.
Montserrat Valdes is a chemical engineer working with CloudLIMS.com. As a QC Chemist and Analytical Chemist, she has conducted numerous accredited testing methods to ensure the quality and compliance of cannabis products, and also validated analytical testing methods and operating, calibrating and troubleshooting a variety of analytical instruments. As a research engineer she has coordinated and published work on various environmental projects ranging from nanotechnology applications to biodegradation and wastewater treatment
1 The Syphilis Study at Tuskegee Timeline. Centres for Disease Control and Prevention. Accessed July 07, 2023. https://www.cdc.gov/tuskegee/timeline.htm
2 ICH: E 6 (R2): Guideline for good clinical practice - Step 5. European Medicines Agency. Published December 01, 2016. Accessed July 07, 2023. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-goodclinical-practice-e6r2-step-5_en.pdf
3 National Covid Cohort Collaborative (N3C). N3C. Accessed July 07, 2023. https://covid.cd2h.org/
4 Improve Data Linkage & Collaboration with Laboratory Software for Clinical Research. CloudLIMS.com. Published April 25, 2023. Accessed July 07, 2023. https://cloudlims.com/leverage-laboratorysoftware-for-clinicalresearch-to-improvedata-linkagecollaboration/
5 Service Advantages of a Cloud-based LIMS. CloudLIMS. com. Accessed July 07, 2023. https://cloudlims.com/lims-white-paper/service-advantagesof-a-cloud-based-lims/