Evaluation of Legal Legislation Compliance and Readability of Clinical Trial Informed Consent Forms
Research Article
Buket Gungor, Mualla Aylin, Ayse Asena, Elif Inci Somuncuoglu, Nihan Burul Bozkurt, Serife Reyhan Ucku, Ayse Gelal
Therapeutic Innovation & Regulatory Science, 19 May 2019
Abstract
Background
The volunteers approached for participation in a clinical trial should be given detailed and understandable information about the study through an informed consent form (ICF) before enrollment. In this study, we evaluated clinical trial files submitted to the Turkish Medicines and Medical Devices Agency (TITCK) to investigate the compliance to legal legislation and readability of ICFs as well as the factors affecting them.
Methods
This is a descriptive, cross-sectional study. We evaluated 160 ICFs in the phase II-IV clinical trial files submitted to TITCK in 2016 to determine their compliance to legislation (n = 160) and to assess their readability (n = 152) using Atesman formula. Overall compliance score was calculated. ICFs were also evaluated in terms of written format (font size, line spacing, section headings) and page count. Statistical analysis was performed with chi-square, Student’s t test, analysis of variance, Mann-Whitney U, and Kruskal Wallis analysis.
Results
Compliance to legislation and suitability of written format of international trial ICFs were significantly higher than those of national trial ICFs. Most of the national trials were investigator initiated. Readability was low in both national and international trial ICFs where the text was longer in the latter.
Conclusion
Results showed that researchers need easy-to-read ICF writing training that fits legal regulations.

Need for greater transparency in documenting informed consent
Commentary
Peter Tugwell, J. Andre Knottnerus
Journal of Clinical Epidemiology, May 2019; 109 pp v–vii
Abstract
Kotz et al. in a Commentary [1] call for a re-examination of patient consent in randomised clinical trials. Although informing potential participants about the aims and procedures of a trial is mandatory when seeking their consent, current practice in obtaining informed consent appears to have been shaped the legal duty of disclosure; consent is seen as an action, concluded by signing a form. In line with this administrative attitude toward informed consent, the procedure is standardly reported in a research article. However, there is evidence that the exact information that is given to potential participants is often not understood by them. This is unacceptable, so the authors argue that details about informed consent procedures of randomized controlled trials should be reported transparently with the essential features of the information for participants summarized in the methods section of a trial report and that the full, original participant information letter is published as supplementary material.

Ethical tensions in the informed consent process for randomized clinical trials in emergency obstetric and newborn care in low and middle-income countries
Debate
Dan K. Kaye, Gershom Chongwe, Nelson K. Sewankambo
BMC Medical Ethics, 27 April 2019; 20(27)
Abstract
Background
There is unanimous agreement regarding the need to ethically conduct research for improving therapy for patients admitted to hospital with acute conditions, including in emergency obstetric care. We present a conceptual analysis of ethical tensions inherent in the informed consent process for randomized clinical trials for emergency obstetric care and suggest ways in which these could be mitigated.
Discussion
A valid consenting process, leading to an informed consent, is a cornerstone of this aspect necessary for preservation and maintenance of respect for autonomy and dignity. In emergency obstetric care research, obtaining informed consent can be problematic, leading to ethical tension between different moral considerations. Potential participants may be vulnerable due to severity of disease, powerlessness or impaired decisional capacity. Time for the consent process is limited, and some interventions have a narrow therapeutic window. These factors create ethical tension in allowing potentially beneficial research while avoiding potential harms and maintaining respect for dignity, human rights, justice and autonomy of the participants.
Conclusion
Informed consent in emergency obstetric care in low- and middle-income countries poses numerous ethical challenges. Allowing research on vulnerable populations while maintaining respect for participant dignity and autonomy, protecting participants from potential harms and promoting justice underlie the ethical tensions in the research in emergency obstetric and newborn care. Those involved in research conduct or oversight have a duty of fair inclusion, to avoid denying participants the right to participate and to any potential research benefits.

Reporting of ethical approval and informed consent in clinical research published in leading nursing journals: a bibliometric analysis
Wu, Y, Howarth, ML, Zhou, C and Cong, W
BMC Medical Ethics, 10 May 2019
Abstract
Background
Ethical considerations play a prominent role in the protection of protect human subjects in clinical research. To date the disclosure of ethical protection in clinical research published in the international nursing journals has not been explored. Our research objective was to investigate the reporting of ethical approval and informed consent in clinical research published in leading international nursing journals.
Methods
We used a research based on bibliometric analysis. All clinical research published in the five leading international nursing journals from the SCI Journal Citation Reports (2017 version) between 2015 and 2017 were retrieved to evaluate for evidence of ethical review.
Results
A total of 2041 citations have been identified from the contents of all the five leading nursing journals that were published between 2015 and 2017. Out of these, 1284 clinical studies have been included in the text to extract the data of ethical review. From these, a total of 87.5% of prospective clinical studies mentioned informed consent. Only 52.9% of those reported that written informed consent had been obtained;3.6% reported oral consent, and 6.8% used other ways such as online consent or completion and return of data collection (such as surveys) to denote assent. Notably, 36.2% of those did not describe the method used to obtain informed consent and merely described that “consent was obtained from participants or participants agreed to join in the research”. Furthermore, whilst 93.7% of clinical studies mentioned ethical approval; 92.5% of those stated the name of ethical committee and interestingly, only 37.1% of those mentioned the ethical approval reference. The rates of reporting ethical approval were different between different study type, country, and whether mentioning financial support (all P<0.05). In addition, positive statistically significant correlations were found between reporting informed consent, reporting written informed consent, reporting ethical approval, naming of ethical committee, and reporting ethical approval reference number in the five leading international nursing journals (all P<0.01).
Conclusion
The reporting of ethics in leading international nursing journals demonstrates progress but improvement of the transparency and the standard of ethical reporting in nursing clinical research is required.

Comprehension and recall from the informed consent process by phase I healthy volunteers before dose administration
Research Article
Rami Tadros, Gillian E Caughey, Sally Johns, Sepehr Shakib
Clinical Trials, 28 February 2019; 16(3)
Abstract
Aims/Background
A fundamental part of all clinical trials is informed consent, reflecting the respect for the volunteer’s autonomy. Research participation is voluntary; therefore, certain aspects of the proposed study must be disclosed so that volunteers can make an informed decision. In this study, we aimed to examine the level of comprehension and recall of healthy volunteers from the informed consent process.
Methods
The study was carried out at a single phase I clinical trials unit. A questionnaire was administered to each volunteer to assess recall of important aspects of the study at the day-1 visit following the informed consent process. The questionnaire contained seven questions regarding study objectives, route, frequency and type of drug administration, adverse effects, number of subjects previously exposed and remuneration. One point was awarded for each correct answer.
Results
A total of 266 volunteers were administered the questionnaire. The mean total score (±standard deviation) for all volunteers was 4.5 ± 1.1 points out of 7, with a range of 0.8–6.7. For all 10 studies, 91% of volunteers responded correctly when answering about the route of administration, and 90% were able to accurately state the correct payment amount. Only 7% were able to repeat the aims of the study correctly.
Conclusion
The poor performance of our study volunteers raises concerns about recall of information prior to study drug administration. This has implications for the volunteer’s safety and ability to provide true informed consent. Interventions to improve recall prior to dosing should be undertaken.

Consent complexities, Ebola, and the fine line between collaboration and exploitation in research conducted during public health emergencies [KEYNOTE]
Nouvet, Elysée
PREA Conference. Ethics and Humanitarian Research: Generating Evidence Ethically. The Fawcett Event Center, The Ohio State University, Columbus, Ohio, March 25-26, 2019. Presentation. Session 9. Keynote 3.
Abstract
Background
There is significant and growing scholarship attending to the experiences and motivations of clinical Tx trial participants in Low and Middle Income Countries (LMICs). A smaller and newer body of research is emerging around perceptions and experiences of research conducted during public health emergencies. This presentation is based on one such Research on Research (RoR) study, the R2HC-funded qualitative study “Perceptions and moral experiences of research conducted during the 2014-16 West Africa Ebola outbreak.”
Objective
This presentation takes West Africans’ first-hand accounts of decisions to support or enroll in EVD research as a point of departure for troubling normative parameters and markers of “consent to research”.
Methodology
Content for this presentation is based on team-based analysis of semi-structured interviews (N=99) with West African EVD study participants, members of research ethics boards, researchers, trial staff, and community leaders.
Findings
Our interviews revealed diverse motivations and aspirations or participating or supporting trials, as well as some frustrations around limited options for engagement and impact. A number of researchers with whom we spoke experienced their decisions to “collaborate” on trials as coerced. Others – participants and community leaders – evidently embraced opportunities to enroll in and/or support trials, but simultaneously connected their voluntariness to conviction of their participation’s impact on lives, to understandings of collective ownership over bio-samples, and/or to hopes for new political subjectivities. Mismatch between consent to trials (where consent includes both enrollment in or collaboration with) and the loaded significances of that consent for many with whom we spoke indicate a need for more localized and critical attention to the logics and significances of consent to research in particular humanitarian emergencies.
Conclusion
Upholding ideals of free and informed consent to research in contexts such as ETCs, where those approached for research are sick, distressed, and quarantined, is never going to be easy. What our research flags is that the complexities of consent during the West Africa EVD epidemic extended beyond the walls of the ETC and beyond infected patients. This in turn supports broadening what normally gets included in discussion of and strategies to uphold consent and voluntariness in humanitarian heath emergency research.