Informed Consent: A Monthly Review
This digest aggregates and distills key content adressing informed consent from a broad spectrum of peer-reviewed journals and grey literature, and from various practice domains and organization types including international agencies, INGOs, governments, academic and research institutions, consortiums and collaborations, foundations, and commercial organizations. We acknowledge that this scope yields an indicative and not an exhaustive digest product.
Informed Consent: A Monthly Review is a service of the Center for Informed Consent Integrity, a program of the GE2P2 Global Foundation. The Foundation is solely responsible for its content. Comments and suggestions should be directed to:
Paige Fitzsimmons, MA
Associate Director, Center for Informed Consent Integrity
GE2P2 Global Foundation
PDF Version: GE2P2 Global_Informed Consent – A Monthly Review_December 2020
The latest in the GE2P2 Global Foundation Center for Informed Consent webinar series was held on November 18th 2020. Speakers Dr. Aoife Daly and Sheila Varadan spoke about aspects of children’s capacity and exercise of consent from their recent articles which appeared in The International Journal of Children’s Rights :: Special Issue, Article 5 of the Convention on the Rights of the Child: Families, Guidance and Evolving Capacities. Full information and the call recording can be found at the Center for Informed Consent Integrity website.
Further to children’s capacity to provide consent and assent, we take special note of six articles which appear throughout this edition of the Monthly Review with their respective abstracts:
Children’s autonomy during medical treatment is explored by Díaz-Pérez et al. in Moral structuring of children during the process of obtaining informed consent in clinical and research settings and Fisher et a. in Young women’s autonomy and information needs in the schools-based HPV vaccination programme: a qualitative study.
Proxy consent for children is examined by House et al. in COVID-19 Trial Enrollment for Those Who Cannot Consent: Ethical Challenges Posed by a Pandemic and Strode et al. in Be legally wise: When is parental consent required for adolescents’ access to pre-exposure prophylaxis (PrEP)?.
The use of comics and cartoons to aid in the consent transaction with children is raised by Ghia et al. in Informing children citizens efficiently to better engage them in the fight against COVID-19 pandemic and Qui et al. in Using a cartoon questionnaire to improve consent process in children: a randomized controlled survey.
Informing children citizens efficiently to better engage them in the fight against COVID-19 pandemic
Jean-Eric Ghia, Sophie Gaulin, Laure Ghia, Laure Garancher, Claude Flamand
Neglected Tropical Diseases, 4 November 2020
Since the beginning of the year, the world’s attention has rightly been focused on the spread of the Coronavirus Disease 2019 (COVID-19) pandemic and the implementation of drastic mitigation strategies to limit disease transmission. However, public health information campaigns tailored to children are very rare. Now more than ever, at a time when some governments are taking populations out of lockdown and youth are returning to schools, children around the world need to fully grasp the modes of transmission of the disease, the health risks, the scientific notions of the immune system, the value of barrier measures, and the progress of scientific research. In the context of the COVID-19 pandemic, comics can be very useful for communicating quickly and effectively abstract and important information to children who might be under the influence of a large amount of sometimes contradictory information. Conveying precise, reliable, and accessible information to children is key in a world overwhelmingly impacted by the outbreak. This should be the role and the responsibility of world health official leaders and governments in compliance with the United Nations Convention on the Rights of the Child. In partnership with mainstream medias, consortia of scientists, communication experts, and education specialists, it is urgent that world leaders engage children in this worldwide public health fight.
COVID-19 and consent for research: Navigating during a global pandemic
Ran D Goldman, Luke Gelinas
Clinical Ethics, 5 November 2020
The modern ethical framework demands informed consent for research participation that includes disclosure of material information, as well as alternatives. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) results in illness that often involves rapid deterioration. Despite the urgent need to find therapy, obtaining informed consent for COVID-19 research is needed. The current pandemic presents three types of challenges for investigators faced with obtaining informed consent for research participation: (1) uncertainty over key information to informed consent, (2) time and pressure constraints, and (3) obligations regarding disclosure of new alternative therapies and re-consent. To mitigate consenting challenges, primary investigators need to work together to jointly promote urgent care and research into COVID-19. Actions they can take include (1) prior plan addressing ways to incorporate clinical research into clinical practice in emergency, (2) consider patients vulnerable with early deliberation on the consent process, (3) seek Legally Authorized Representatives (LARs), (4) create a collaborative research teams, (5) aim to consent once, despite evolving information during the pandemic, and (6) aim to match patients to a trial that will most benefit them. The COVID-19 pandemic both exacerbates existing challenges and raises unique obstacles for consent that require forethought and mindfulness to overcome. While research teams and clinician-investigators will need to be sensitive to their own contexts and adapt solutions accordingly, they can meet the challenge of obtaining genuinely informed consent during the current pandemic.
COVID-19 Trial Enrollment for Those Who Cannot Consent: Ethical Challenges Posed by a Pandemic
Samantha A. House, Catherine D. Shubkin, Tim Lahey, Jeffrey P. Brosco, John Lantos
Pediatrics, November 2020, 146(5)
The current coronavirus disease 2019 (COVID-19) pandemic has triggered an intense global research effort to inform the life-saving work of frontline clinicians who need reliable information as soon as possible. Yet research done in pressured circumstances can lead to ethical dilemmas, especially for vulnerable research subjects. We present the case of a child with neurocognitive impairment who is diagnosed with COVID-19 infection after presenting with fever and a seizure. The child lives in a group home and is in the custody of the state; her parents lost parental rights many years ago. Some members of the health care team want to enroll her in a randomized clinical trial evaluating an experimental treatment of COVID-19. For minor patients to enroll in this clinical trial, the institutional review board requires assent of patients and consent of guardians. An ethics consult is called to help identify relevant concerns in enrollment. In the accompanying case discussion, we address historical perspectives on research involving people with disabilities; proper management of research participation for people with disabilities including consent by proxy, therapeutic misconception, and other threats to the ethical validity of clinical trials; and the potentially conflicting obligations of researchers and clinicians.
Informed consent disclosure to vaccine trial subjects of risk of COVID‐19 vaccines worsening clinical disease
Timothy Cardozo, Ronald Veazey
The International Journal of Clinical Practice, 28 October 2020
Aims of the study
Patient comprehension is a critical part of meeting medical ethics standards of informed consent in study designs. The aim of the study was to determine if sufficient literature exists to require clinicians to disclose the specific risk that COVID‐19 vaccines could worsen disease upon exposure to challenge or circulating virus.
Methods used to conduct the study
Published literature was reviewed to identify preclinical and clinical evidence that COVID‐19 vaccines could worsen disease upon exposure to challenge or circulating virus. Clinical trial protocols for COVID‐19 vaccines were reviewed to determine if risks were properly disclosed.
Results of the study
COVID‐19 vaccines designed to elicit neutralizing antibodies may sensitize vaccine recipients to more severe disease than if they were not vaccinated. Vaccines for SARS, MERS and RSV have never been approved, and the data generated in the development and testing of these vaccines suggest a serious mechanistic concern: that vaccines designed empirically using the traditional approach (consisting of the unmodified or minimally modified coronavirus viral spike to elicit neutralizing antibodies), be they composed of protein, viral vector, DNA or RNA and irrespective of delivery method, may worsen COVID‐19 disease via antibody‐dependent enhancement (ADE). This risk is sufficiently obscured in clinical trial protocols and consent forms for ongoing COVID‐19 vaccine trials that adequate patient comprehension of this risk is unlikely to occur, obviating truly informed consent by subjects in these trials.
Conclusions drawn from the study and clinical implications
The specific and significant COVID‐19 risk of ADE should have been and should be prominently and independently disclosed to research subjects currently in vaccine trials, as well as those being recruited for the trials and future patients after vaccine approval, in order to meet the medical ethics standard of patient comprehension for informed consent.
Informed consent for Orthopaedic surgeons in the time of COVID-19: Addressing ‘the elephant in the room’
Sohail Yousaf, Syed Hassan, Paul Hamilton, Andrea Sott
BMJ Quality & Safety, 18 June 2020
…The doctor-patient conversation that occurs following the diagnosis of such an injury is important to fulfilling ethical and professional responsibilities and reducing medico-legal risk. Understanding the patient’s future goals and expectations influences management and is vital to shared decision-making. Surgeons need to enable patients to be fully informed by giving them high quality information about the current evidence base regarding the proposed treatment and the available alternatives and risks…
Reflections on dynamic consent in biomedical research: the story so far
Harriet J. A. Teare, Megan Prictor, Jane Kaye
European Journal of Human Genetics, 28 November 2020
Dynamic consent (DC) was originally developed in response to challenges to the informed consent process presented by participants agreeing to ‘future research’ in biobanking. In the past 12 years, it has been trialled in a number of different projects, and examined as a new approach for consent and to support patient engagement over time. There have been significant societal shifts during this time, namely in our reliance on digital tools and the use of social media, as well as a greater appreciation of the integral role of patients in biomedical research. This paper reflects on the development of DC to understand its importance in an age where digital health is becoming the norm and patients require greater oversight and control of how their data may be used in a range of settings. As well as looking back, it looks forwards to consider how DC could be further utilised to enhance the patient experience and address some of the inequalities caused by the digital divide in society.
Details of risk–benefit communication in informed consent documents for phase I/II trials
Hannes Kahrass, Sabine Bossert, Christopher Schürmann, Daniel Strech
Clinical Trials, 24 November 2020
Informed consent documents for clinical studies should disclose all reasonably foreseeable risks and benefits. Little guidance exists on how to navigate the complexities of risk–benefit communication, especially in early clinical research. Practice-oriented development of such guidance should be informed by evidence on what and how details of risks and benefits are currently communicated.
We surveyed the responsible parties of phase I/II trials registered in ClinicalTrials.gov that started 2007 or later and completed between 2012 and 2016 to sample informed consent documents from a broad spectrum of early phase clinical trials. Based on an assessment matrix, we qualitatively and quantitatively assessed the informed consent documents for details of risk–benefit communication.
The risk–benefit communication in the 172 informed consent documents differed substantially in several regards. The outcome, extent, and likelihood of health risks, for example, were described in 83%, 32%, and 63% of the informed consent documents. Only 45% of informed consent documents specified the outcome of mentioned health benefits, and the extent and likelihood of health benefits were never specified. From those informed consent documents reporting risk likelihoods, only 57% added frequency numbers to words such as “common” or “rare,” and even in these cases, we found strong variations for presented frequency ranges. Substantial heterogeneity also exists for how informed consent documents communicate other risk and benefit types and related safeguards.
Our study points to several shortcomings and heterogeneities in how informed consent documents communicate risks and benefits to potential research participants. Health risks, for example, should be specified with frequency numbers, and health benefits should be specified at least by mentioning their outcomes. Further demand for research and policy development is needed to harmonize risk–benefit communication and to clarify ways to specify the likelihood of health benefits.
Differences in demographics and outcomes based on method of consent for a randomised controlled trial on heat loss prevention in the delivery room
Sunita Vohra, Maureen Reilly, Valeria E Rac, Zafira Bhaloo, Denise Zayak, John Wimmer, Michael Vincer, Karla Ferrelli, Alex Kiss, Roger Soll, Michael Dunn
Archives of Disease in Childhood – Fetal and Neonatal Edition, 24 November 2020
Informed consent is standard in research. International guidelines allow for research without prior consent in emergent situations, such as neonatal resuscitation. Research without prior consent was incorporated in the Vermont Oxford Network Heat Loss Prevention Trial. We evaluated whether significant differences in outcomes exist based on the consent method.
Subgroup analysis of infants enrolled in a randomised controlled trial conducted from 2004 to 2010.
A multicentre trial with 38 participating centres.
Infants born 24–27 weeks of gestation. 3048 infants assessed, 2231 excluded due to fetal congenital anomalies, failure to obtain consent or gestation less than 24 weeks. 817 randomised, 4 withdrew consent, total of 813 analysed.
Main outcome measure
The difference in mortality between consent groups.
No significant differences were found in mortality at 36 weeks (80.2%, 77.4%, p=0.492) or 6 months corrected gestational age (80.7%, 79.7%, p=0.765). Infants enrolled after informed consent were more likely to have mothers who had received antenatal steroids (95.2%, 84.0%, p<0.0001). They also had significantly higher Apgar scores at 1 (5.0, 4.4, p=0.019), 5 (7.3, 6.7, p=0.025) and 10 min (7.5, 6.3, p=0.0003).
Conclusions and relevance
Research without prior consent resulted in the inclusion of infants with different baseline characteristics than those enrolled after informed consent. There were no significant differences in mortality. Significantly higher Apgar scores in the informed consent group suggest that some of the sicker infants would have been excluded from enrolment under informed consent. Research without prior consent should be considered in neonatal resuscitation research.
A systematic review of risk communication in clinical trials: How does it influence decisions to participate and what are the best methods to improve understanding in a trial context?
Maeve Coyle, Katie Gillies
PLOS One, 16 November 2020
Effective risk communication is challenging. Ensuring potential trial participants’ understand ‘risk’ information presented to them is a key aspect of the informed consent process within clinical trials, yet minimal research has looked specifically at how to communicate probabilities to support decisions about trial participation. This study reports a systematic review of the literature focusing on presentation of probabilistic information or understanding of risk by potential trial participants.
A search strategy for risk communication in clinical trials was designed and informed by systematic reviews of risk communication in treatment and screening contexts and supplemented with trial participation terms. Extracted data included study characteristics and the main interventions/findings of each study. Explanatory studies that investigated the methods for presenting probabilistic information within participant information leaflets for a clinical trial were included, as were interventions that focused on optimising understanding of probabilistic information within the context of a clinical trial.
The search strategy identified a total of 4931 studies. Nineteen papers were selected for full text screening, and seven studies included. All reported results from risk communication studies that aimed to support potential trial participants’ decision making set within hypothetical trials. Five of these were randomised comparisons of risk communication interventions, and two were prospectively designed, non-randomised studies. Study interventions focused on probability presentation, risk framing and risk interpretation with a wide variety of interventions being evaluated and considerable heterogeneity in terms of outcomes assessed. Studies show conflicting findings when it comes to how best to present information, although numerical, particularly frequency formats and some visual aids appear to have promise.
The evidence base surrounding risk communication in clinical trials indicates that there is as yet no clear optimal method for improving participant understanding, or clear consensus on how it affects their willingness to participate. Further research into risk communication within trials is needed to help illuminate the mechanisms underlying risk perception and understanding and provide appropriate ways to present and communicate risk in a trial context so as to further promote informed choices about participation. A key focus for future research should be to investigate the potential for learning in the evidence on risk communication from treatment and screening decisions when applied to decisions about trial participation.