A Census of Clinical Trials Conducted Under the US Exception from Informed Consent Rule

A Census of Clinical Trials Conducted Under the US Exception from Informed Consent Rule
Krista L. Snyder, Jon F. Merz
medRxiv, 24 August 2022
Abstract
Background
The US Food and Drug Administration and National Institutes of Health adopted the Exception from Informed Consent (EFIC) rule in 1996, permitting waiver of informed consent for certain emergency research, including trials funded by the federal government. The rule requires that prospective consent be sought when practicable from patients or their Legally Authorized Representative(s) (LAR), and for those enrolled without consent, the patient or their LAR must be given information and an opportunity to opt-out from continued participation at the earliest opportunity. We sought to census the trials conducted under the EFIC rule to facilitate research to better understand how the rule is being used.
Methods
We conducted a multi-pronged search to try and identify all trials conducted under the EFIC rule, drawing on numerous reviews, Medline and Google searches (including of the clinicaltrials.gov registry), examination of the FDA’s docket, posting an inquiry on the IRB Forum, and email requests to lead authors of all published EFIC trials and related review articles. We describe the trials, when they were started and completed, and whether they were terminated early.
Results
We identified a total of 105 trials as of April 1, 2022: 77 complete, 10 recruiting, 10 registered on clinicaltrials.gov but not yet recruiting, 5 trials that were abandoned before enrolling any subjects, and 3 trials in early planning. Nine of the 77 completed trials were pilot or feasibility trials. Of 68 completed full trials, 30 (44.1%) were terminated early. The most common reason for early termination was futility or safety (17 trials, 25.0%) followed by poor recruitment (9 trials, 13.2%). The rate of conduct of trials has been remarkably constant since 2001, with roughly 18 trials started in each 5-year period.
Conclusions
The rate of early termination of EFIC trials for futility or safety appears higher than for other kinds of clinical research. We provide the list of trials in a Supplement for further in-depth data collection and analysis of this set of trials.

Use Of Teach-Back During Informed Consent In Cancer Clinical Trials

Use Of Teach-Back During Informed Consent In Cancer Clinical Trials
Christa Varnadoe
Yale School of Nursing Digital Theses, 2022
Open Access
Abstract
Five percent of the 1.8 million patients diagnosed with cancer in the United States (US) enroll annually in a clinical trial (American Cancer Society, 2021; Institute of Medicine Committee on Cancer Clinical Trials; National Cancer Institute Cooperative Group Program, 2010). Flawed research consent practices are detrimental to patient safety and costly to the US Healthcare system (Eisenberg et al., 2012; Unger et al., 2019). Well trained nurses are imperative to conducting rigorous, reproducible, and quality research (Brandt et al., 2011). Programs designed to educate nurses on how to implement comprehensive communication strategies confidently during the Cancer Clinical Trials (CCT) consent process remain scarce (Nusbaum et al, 2019; Purdom et al., 2017). The purpose of this quality improvement project was to develop, implement, and evaluate the effects of an evidenced-based education program on nurse confidence with use of the teach-back method during the CCT consent process. An evidenced based education program was developed. It was implemented as a synchronous webinar to members of the International Association of Clinical Research Nurses. Pre and post test program surveys measuring confidence levels were disseminated. There was an overall increase in postsurvey responses suggesting an improvement in confidence levels with use of the teach-back method during the CCT IC process. Further study can explore if patient understanding of CCTs during the IC process is developed proportionally to levels of nurse confidence with use of the teach-back method.

Ethical Considerations during the Informed Consent Process for Acute Ischemic Stroke in International Clinical Trials

Ethical Considerations during the Informed Consent Process for Acute Ischemic Stroke in International Clinical Trials
Tiffany Bellomo, Jennifer Fokas, Noah Tsao, Clare Anderson, Christopher Becker, Rachel Gioscia-Ryan, William Meurer
Ethics & Human Research, 8 July 2022; 44(4) pp 14-25
Abstract
We sought to investigate the experiences of researchers in existing active-control trials in acute ischemic stroke comparing investigational therapy to tissue plasminogen activator (tPA) in order to identify the approaches and challenges in obtaining informed consent. Out of 401 articles evaluated, 14 trials met inclusion criteria. Trial representatives were contacted to complete a survey concerning the consent process. None of the 14 trials published materials related to the informed consent process. Trials with 75% to 100% of patients directly consented had shorter door-to-treatment (DTT) times than trials that directly consented less than 50% of patients. Trials that had translators available (for recruiting participants who were not native speakers in the local language) and translated consent documents had longer DTT times. The study findings suggest that differences in the standards of informed consent internationally may allow more patients with moderate strokes to provide direct consent without delaying DTT time. Future trials should emphasize transparency to the public and scientific community in the informed consent process.

Developing and Implementing Electronic Consent Procedures in Response to Covid-19 Restrictions

Developing and Implementing Electronic Consent Procedures in Response to Covid-19 Restrictions
Julie R. Bromberg, Evelyn Nimaja, Andrew W. Kiragu, Karla A. Lawson, Lois Lee, Isam W. Nasr, Charles Pruitt, Stephanie M. Ruest, Michael J. Mello
Ethics & Human Research, 8 July 2022; 44(4) pp 34-38
Open Access
Abstract
The Covid-19 pandemic resulted in unprecedented restrictions on many public, private, and workplace activities throughout the United States and elsewhere. When restrictions were imposed, we were conducting a type III hybrid effectiveness-implementation trial in 10 pediatric trauma centers. In response to several pandemic-based restrictions, we had to develop procedures for engaging with potential research participants while limiting nonclinical, in-person interactions. This manuscript describes the procedures and challenges of obtaining electronic informed consent and assent in a multisite trauma center-based research study. We developed, tested, and trained staff to implement three options for obtaining informed consent. Twenty-five participants were enrolled in the effectiveness-implementation multisite trial during the first six months of utilization of the consent options, with eleven of these individuals enrolled using hybrid or electronic consent procedures. The challenges we identified involving electronic consent procedures included confusion over who would complete the electronic consent process and difficulties reconnecting with families. Lessons learned can strengthen electronic consent and assent procedures for future studies. More research is needed to further strengthen this process and increase its utilization.

Issues About Digital Informed Consent in Clinical Research

Issues About Digital Informed Consent in Clinical Research
Freade Akbar, Ray Wagiu Basrowi
Indonesian Journal of Community and Occupational Medicine, July 2022; 2(1) pp 40-7
Open Access
Abstract
Introduction
Informed consent is a concrete form of moral and ethical values that urgently needs to be emphasized, especially in research that requires the role of humans as subjects and is commonly associated with experimental research. Informed consent itself consists of two forms of print and digital, along with the times many parties began to examine how the role of informed consent, the advantages and disadvantages between print and digital, the application of good digital informed consent, and how information about research should be conveyed to the research subject so that it is easy to understand and in accordance with moral and ethical standards. The purpose of this article is to address issues related to digital informed consent in clinical research.
Methods
We conducted a search on the SpingerLink database in March 2022 to see various publications in the last 2 years related to electronic informed consent using keywords: digital, informed consent, research.
Results
Total 4 articles as source of literature review. Recent research shows the tendency of research subjects to choose digital informed consent because content is easier to personalize, makes it easier to understand content that is only needed by the subject, and the ease of adding digital content in certain forms of media such as audio, and video into digital formats. From the researcher’s side will increase the active participation and number of study subjects, making it easier for long-term interaction, especially follow-up research. There are 4 types of informed consent based on utilization for research and 5 informed consent processes that must be carried out in clinical research, which is attempted using language that is easily understood by the research subject and dynamic for further research.
Conclusions
Informed consent in any form constitutes the autonomy right of the subject. Digital formats provide better prospects in facilitating communication to research subjects. But this ease must be accompanied by the consistency of the application of the standard informed consent process, even in intervention studies with biological samples this is more stringent. Informed consent given to the subject must use language that is easy to understand, and transparent. The subject of the study is given the right at any time to exit the research. In the future, the issue of morals and ethics of research will grow, and more dynamic informed consent is needed, especially for interventional clinical research.

Keys to improving the informed consent process in research: Highlights of the i-CONSENT project

Keys to improving the informed consent process in research: Highlights of the i-CONSENT project
Editorial
Jaime Fons-Martinez, Cristina Ferrer-Albero, Javier Diez-Domingo
Health Expectations, 27 July 2022
Open Access
Excerpt
    The ethical and legal governance of all aspects of informed consent in research is becoming increasingly extensive and complex. Instead of a single directive, informed consent is governed by a series of international rules applied to biomedical research, clinical trials and biobanks, while various ethical guidelines for research have been published by different international bodies.

Informed consent is an essential part of any research involving humans, but the array of available guidelines can complicate the informed consent process for sponsors, researchers and participants. Sponsors, in particular, find it difficult to adapt the informed consent process to the characteristics of the participants. Moreover, because of the length and complexity of informed consents, some participants may misconstrue key points and agree to participate in a trial that they do not fully understand. In these cases, the decision on their participation is mainly based on discussions with the researcher, which lacks traceability…

Success rate of acquiring informed consent and barriers to participation in a randomized controlled trial of laparoscopic versus open surgery for non-curative stage IV colon cancer in Japan

Success rate of acquiring informed consent and barriers to participation in a randomized controlled trial of laparoscopic versus open surgery for non-curative stage IV colon cancer in Japan
Journal Article
Tomonori Akagi, Kosuke Suzuki, Yohei Kono, Shigeo Ninomiya, Tomotaka Shibata, Yoshitake Ueda, Hidefumi Shiroshita, Tsuyoshi Etoh, Akio Shiomi, Masaaki Ito, Jun Watanabe, Kohei Murata, Yasumitsu Hirano, Manabu Shimomura, Shunsuke Tsukamoto, Yukihide Kanemitsu, Masafumi Inomata
Japanese Journal of Clinical Oncology, 22 July 2022
Abstract
Background
Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC.
Methods
A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires.
Results
In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients’ preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization.
Conclusions
The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

Future informed consent research – a step in the wrong direction!

Future informed consent research – a step in the wrong direction!
JM Clements, LJ Convie, SJ Kirk, M Clarke
British Journal of Surgery, 22 July 2022; 109(Suppl 4)
Open Access
Abstract
Introduction
Over 300 million invasive procedures occur globally every year, each requiring patient informed consent. No single outcome measure exists for measurement of the informed consent process. A core outcome set (COS) for informed consent for therapy consisting of 9 outcomes has been developed to define what outcomes matter to key stakeholders in the informed consent process. We aimed to identify the frequency of uptake of the COS consent outcomes in future randomised control trials.
Methods
A systematic review of prospectively registered randomised control trial protocols was performed. The online trial registries World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP) and the US National Library of Medicine ClinicalTrials.gov were searched. All studies assessing interventions designed to improve the informed consent process were considered.
Results
627 registered protocols were identified of which 22 met the inclusion criteria. Only two core outcomes were reported in any prospective interventional consent trial protocols. Patient satisfaction with the consent process and patient satisfaction with the amount of information were observed which employed unvalidated tools. Patient knowledge was the predominant primary outcome measure (n=20). Unvalidated measurement tools were used in all cases. Patient anxiety, decisional regret and decisional conflict were the only outcomes consistently measured using validated measurement tools.
Conclusion
The use of unvalidated outcome measurement tools in future consent trials are widespread. This review has highlighted the clear disconnect between chosen outcomes in future consent trial protocols and an established informed consent COS, limiting the potential value of outputs in future consent trials.
Take-home message
A clear disconnect exists between the outcome measures used in prospective consent randomised trials and an established core outcome set for informed consent for therapy.

When is it impractical to ask informed consent? A systematic review

When is it impractical to ask informed consent? A systematic review
Review Article
Sara JM Laurijssen, Rieke van der Graaf, Wouter B van Dijk, Ewoud Schuit, Rolf HH Groenwold, Diederick E Grobbee, Martine C de Vries
Clinical Trials, 1 July 2022
Abstract
Background
Informed consent is one of the cornerstones of biomedical research with human subjects. Research ethics committees may allow for a modification or a waiver of consent when the research has social value, involves minimal risk, and if consent is impractical to obtain. While the conditions of social value and minimal risk have received ample attention in research ethics literature, the impractical condition remains unclear. There seem to be different interpretations of the meaning of impractical within academic literature. To address this lack of clarity, we performed a systematic review on the interpretation of impractical.
Methods
First, we examined international research ethics guidelines on their usage and interpretation of impractical. Next, we used international ethical guidelines to identify synonyms of the term “impractical.” Accordingly, PubMed, Embase, and Web of Science were searched for articles that included “informed consent” and “impractical” or one of its synonyms.
Results
We found that there were only a few international ethics guidelines that described what could be considered impractical. Out of 2329 identified academic articles, 42 were included. Impractical was used to describe four different conditions: (1) obtaining informed consent becomes too demanding for researchers, (2) obtaining informed consent leads to invalid study outcomes, (3) obtaining informed consent harms the participant, and (4) obtaining informed consent is meaningless for the participant.
Conclusion
There are conditions that render conventional informed consent truly impractical, such as untraceable participants or harm for participants. At the same time, researchers have a moral responsibility to design an infrastructure in which consent can be obtained, even if they face hardship in obtaining consent. In addition, researchers should seek to minimize harm inflicted upon participants when harm may occur as a result of the consent procedure. Invalidity of research due to consent issues should not be regarded as impractical but as a condition that limits the social value of research. Further research is essential for when a waiver of informed consent based on impractical is also reasonable.

Toward Meeting the Obligation of Respect for Persons in Pragmatic Clinical Trials

Toward Meeting the Obligation of Respect for Persons in Pragmatic Clinical Trials
Morain SR, Kraft SA, Wilfond BS, Mcguire A, Dickert NW, Garland A, Sugarman J
The Hastings Center Report, 1 May 2022; 52(3) pp 9-17
Abstract
Research ethics oversight systems have traditionally emphasized the informed consent process as the primary means by which to demonstrate respect for prospective subjects. Yet how researchers can best fulfill the ethical obligations of respect for persons in pragmatic clinical trials (PCTs)-particularly those that may alter or waive informed consent-remains unknown. We propose eight dimensions of demonstrating respect in PCTs: (1) engaging patients and communities in research design and execution, (2) promoting transparency and open communication, (3) maximizing agency, (4) minimizing burdens and promoting accessibility, (5) protecting privacy and confidentiality, (6) valuing interpersonal interactions with clinicians and study team members, (7) providing compensation, and (8) maximizing social value. While what respect requires in the context of PCTs will vary based on the nature of the PCT in question, the breadth of these dimensions demonstrates that respect obligations extend beyond informed consent processes.