Improvement of Informed Consent Document Management in Clinical Trials Using an Electronic Medical Record System
Takahiro Kawakami, Katsuhiko Nagase, Yuko Yokoi, Yoshimichi Sai, Toshinori Murayama
Clinical Pharmacology, 2019; 50(3) pp 81-86
Abstract
Background
This study aims to systematize quality assurance and document management support to ensure the smooth implementation of investigator-initiated clinical trials (IITs).
Methods
A sample survey was performed to investigate whether and how signed original informed consent (IC) documents for IITs were stored at Kanazawa University Hospital. Based on the findings, initiatives were implemented utilizing an electronic medical record (EMR) system: 1) The latest versions of IC forms were issued directly from the EMRs for version control. Forms were printed with a 2D barcode to facilitate their re-entry into subjects’ medical records. 2) A new management protocol was introduced in the clinical trial support office to ensure consistent uploading processes for signed IC documents and the archiving of paper records. 3) Patients were registered to trials individually using their EMRs, enabling investigators to access their consent and progress statuses in one place. After implementing these initiatives, the storage of signed original IC documents was re-assessed.
Results
The EMR system presented a simpler IC document management compared to the conventional approach. The updated post-consent document handling procedure improved and consolidated signed original IC document archiving. In addition to the separate registration of trial subjects, investigators responsible for the trial were explicitly identified in the EMR system in the event of uncertainty in other departments. This approach allows for easy confirmation of subjectsʼ consent status when preparing and administering trial drugs.
Conclusions
Our approach of consolidated document and trial process management can improve the reliability of clinical research.

Editor’s note: This a Japanese language publication. Kanazawa University Hospital operates in Kanazawa, Ishikawa, Japan.

Clinical Image Consent Requirements: Variability among Top Ten Medical Journals
Juan N. Lessing, Nicholas M. Mark, Matthew K. Wynia, Ethan Cumbler
Journal of Academic Ethics, 21 June 2019; pp 1–5
Abstract
The consent process for publication of clinical images in medical journals varies widely. The extent of this variation is not known. It is also not known whether journals follow their own stated best practices or the guidance of the International Committee of Medical Journal Editors (ICMJE). We assessed consent requirements in a sample of 10 top impact factor general medicine journals that publish clinical images, examining variability in consent requirements for clinical image publication and congruence of requirements with the recommendations of the ICMJE. Clinical image consent requirements varied widely from journal to journal. None of the studied journals, even amongst n = 4 ICMJE members or n = 8 journals who self-report adherence to ICMJE guidelines, comply with all of the recommendations of the ICMJE. Half of studied journals require a journal-specific consent form. Among top medical journals there is significant heterogeneity in consent requirements for clinical images. Variability of consent requirements is neither practical nor rational; inconsistent requirements create uncertainty for authors, present impediments to dissemination of scholarship, and undermine a shared professional understanding of how best to protect patient privacy. We propose adopting a standardized consent form and process for publication of identifiable images in medical journals, with uniform elements and explicit definitions.

The Effect of Framing and Placement on Linkage Consent 
Joseph W Sakshaug, Alexandra Schmucker, Frauke Kreuter, Mick P Couper, Eleanor Singer
Public Opinion Quarterly, 20 June 2019
Abstract
Numerous surveys link interview data to administrative records, conditional on respondent consent, in order to explore new and innovative research questions. Optimizing the linkage consent rate is a critical step toward realizing the scientific advantages of record linkage and minimizing the risk of linkage consent bias. Linkage consent rates have been shown to be particularly sensitive to certain design features, such as where the consent question is placed in the questionnaire and how the question is framed. However, the interaction of these design features and their relative contributions to the linkage consent rate have never been jointly studied, raising the practical question of which design feature (or combination of features) should be prioritized from a consent rate perspective. We address this knowledge gap by reporting the results of a placement and framing experiment embedded within separate telephone and Web surveys. We find a significant interaction between placement and framing of the linkage consent question on the consent rate. The effect of placement was larger than the effect of framing in both surveys, and the effect of framing was only evident in the Web survey when the consent question was placed at the end of the questionnaire. Both design features had negligible impact on linkage consent bias for a series of administrative variables available for consenters and non-consenters. We conclude this research note with guidance on the optimal administration of the linkage consent question.

Linking Survey and Twitter Data: Informed Consent, Disclosure, Security and Archiving
Luke Sloan, Curtis Jessop, Tarek Al Baghal, Matthew Williams
University of Essex Research Repository, 11 June 2019
Abstract
Linked survey and Twitter data present an unprecedented opportunity for social scientific analysis, but the ethical implications for such work are complex – requiring a deeper understanding of the nature and composition of Twitter data to fully appreciate the risks of disclosure and harm to participants. In this paper we draw on our experience of three recent linked data studies, briefly discussing the background research on data linkage and the complications around ensuring informed consent. Particular attention is paid to the vast array of data available from Twitter and in what manner it might be disclosive. In light of this, the issues of maintaining security, minimising risk, archiving and re-use are applied to linked Twitter and survey data. In the conclusion we reflect on how our ability to collect and work with Twitter data has outpaced our technical understandings of how the data is constituted and observe that understanding one’s data is an essential prerequisite for ensuring best ethical practice.

A limited number of medicines pragmatic trials had potential for waived informed consent following the 2016 CIOMS ethical guidelines
Original Article
Rafael Dal−Ré, Cristina Avendaño−Solà, Anthoniusde Boer, Stephan K. James, Frits R. Rosendaal, Richard Stephens, John PA Ioannidis
Journal of Clinical Epidemiology, 15 June 2019
Abstract
Objective
European regulations do not allow modification or waiver of informed consent for medicines randomized controlled trials (RCTs) where the three 2016 Council for International Organizations of Medical Sciences (CIOMS) provisions are met (consent would be impractical or unfeasible, yet the trial would have high social value and pose no or minimal risk to participants). We aimed to identify whether any such trials of medicines were being conducted in Europe.
Study design and Setting
Survey of all phase 4 ‘ongoing’ RCTs on the EU clinical trial register between 1/July/2016 and 30/June/2018, to identify those with potentially high levels of pragmatism. Trials that were excluded: those conducted on rare diseases; masked (single-, double-blind) trials; single-center trials; those where one could expect to lead patients to prefer one intervention over the other; and miscellaneous reasons. The degree of pragmatism of the RCTs was self-assessed by trials’ investigators by means of the PRECIS-2 tool. Investigators of those trials considered to be highly pragmatic, assessed the fulfillment of the three CIOMS provisions. Seven patients assessed the social value of the RCTs. Finally, 33 members of 11 research ethics committees (RECs) assessed the social value of the trials and whether they posed no more than minimal risk to participants. Investigators, patients and REC members assessed the fulfilment of the CIOMS provisions as ‘Yes’, ‘Not sure’ or ‘No’.
Results
Of the 636 phase 4 trials, 420 were RCTs, and 21 of these (5%) were candidates to be pragmatic. Investigators of 15 of these 21 RCTs self−assessed their trial’s degree of pragmatism: 14 were highly pragmatic. Of these 14, eight fulfilled the three CIOMS provisions. Assessments by patients and RECs were inconsistent for several trials.
Conclusions
We found few low−risk participant−level pragmatic RCTs that could be suitable for modified or waived participants’ informed consent. European regulators should consider amending the current regulation and encouraging the conduct of such trials.

Informed consent for early-phase clinical trials: therapeutic misestimation, unrealistic optimism and appreciation
Original research
Jodi Halpern, David Paolo, Andrew Huang
BMJ, 12 June 2019
Abstract
Unrealistic therapeutic beliefs are very common—the majority of patient-subjects (up to 94%) enrol in phase 1 trials seeking and expecting significant medical benefit, even though the likelihood of such benefit has historically proven very low. The high prevalence of therapeutic misestimation and unrealistic optimism in particular has stimulated debate about whether unrealistic therapeutic beliefs in early-phase clinical trials preclude adequate informed consent. We seek here to help resolve this controversy by showing that a crucial determination of when such therapeutic beliefs are ethically problematic turns on whether they are causally linked and instrumental to the motivation to participate in the trial. Thus, in practice, it is ethically incumbent on researchers to determine which understanding and beliefs lead to the participant’s primary motivation for enrolling, not to simply assess understanding, beliefs and motivations independently. We further contend that assessing patient-subjects’ appreciation as a component of informed consent—it is already an established component of decision-making capacity assessments—can help elucidate the link between understanding-beliefs and motivation; appreciation refers to an individual’s understanding of the personal significance of both the medical facts and the experience of trial participation. Therefore, we recommend that: (1) in addition to the usual question, ‘Why do you want to participate in this trial?’, all potential participants should be asked the question: ‘What are you giving up by participating in this trial?’ and (2) researchers should consider the settings in which it may be possible and practical to obtain ‘two-point consent’.

Informed Consent Issues for Cell Donors
Methods in Molecular Biology book series
Insoo Hyun
Chimera Research, 8 June 2019; pp 67-74
Abstract
Stem cell-based chimera research depends on the free and voluntary provision of human biomaterials necessary for the derivation of pluripotent stem cell lines. Informed consent requirements for the procurement of human embryos, gametes, and somatic cells must take into account unique features of biomedical research involving the use of immortal cell lines that carry their donors’ genetic information. The extent and basis for donors’ rights, including the right to withdraw from research, are explored here in detail.

Parents’ and clinicians’ views on conducting paediatric diagnostic test accuracy studies without prior informed consent: qualitative insight from the Petechiae in Children study (PiC)
Original Article
Thomas Waterfield, Mark D Lyttle, Michael Shields, Derek Fairley, Damian Roland, James McKenna, Kerry Woolfall
BMJ, 7 June 2019
Abstract
Objective 
The Petechiae in Children (PiC) study assesses the utility of presenting features and rapid diagnostic tests in the diagnosis of serious bacterial infection in feverish children with non-blanching rashes. An embedded qualitative study explored parents’ and clinicians’ views on the acceptability of the PiC study, including the use of research without prior consent (RWPC) in studies of diagnostic test accuracy.
Design 
Semistructured qualitative interviews. Analysis was thematic and broadly interpretive, informed by the constant comparative approach.
Participants 
Fifteen parents were interviewed 55 (median) days since their child’s hospital attendance (range 13–95). Five clinicians involved in recruitment, and consent were interviewed.
Results 
Parents and clinicians supported RWPC for the PiC study and future emergency paediatric diagnostic test accuracy studies as long as there is no harm to the child and emergency care is not delayed. Parents and clinicians made recommendations around the timing and conduct of a consent discussion, which were in line with RWPC guidance. Parents enrolled in the PiC study preferred a design that included consent discussions with the research team over the alternative of ‘opt-out’ consent only.
Conclusions 
This embedded qualitative study demonstrates that RWPC is appropriate for use in paediatric emergency studies of diagnostic test accuracy and that the approach used in PiC was appropriate. Future diagnostic studies involving additional invasive procedures or an opt-out only approach to consent would benefit from exploring parent and clinician views on acceptability at the pretrial stage.

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.