Randomized, Double-Blind Trial on the Impact of Word Count in Cancer Clinical Trial Consent Forms
Yahya Almodallal, Quyen Duong, Daniel Satele, Paul Novotny, Kathryn D. Cook , Cynthia Chauhan, Michelle K. Daiss, Jennifer Le-Rademacher, Sherry Looker, Nichole Martin, Michanda F. Smestad, Stacey J. Winham, Sumithra J. Mandrekar, Aminah Jatoi
JCO Oncology Practice, 14 June 2021
This randomized, double-blind study sought to understand whether cancer clinical trial consent form verbosity detracts from patients’ decision making on trial enrollment.
This trial tested mock consent forms of 2,000, 4,000, and 6,000 words. The first two comprised the two experimental arms and the third the control arm. Phase II was conducted to identify the promising arm, which, in phase III, was compared with the control arm. Each consent form described the same trial. Eligible adult patients reported a cancer history and English literacy. The primary end point used a patient-reported Likert scale to assess the relationship between information in the consent form and trial decision making.
In phase II, 93 patients were accrued and prompted the selection of the 2,000-word consent form for phase III. In phase III, 182 patients were recruited, resulting in 240 total evaluable patients to compare the 2,000-word versus the 6,000-word arm (control). For the primary end point, 103 (84%) and 107 (91%) patients in the 2,000- and 6,000-word arms, respectively, strongly agreed or agreed with the following: “The information in this consent form helped me make a decision about whether or not to enroll in the trial” (two-sided, P = .14). Median time to read each consent form was 8 and 12 minutes, respectively (two-sided, P < .0001). Among those assigned these consent forms, 84% and 73%, respectively (two-sided, P = .04) signed or expressed a willingness to sign.
This study’s primary end point was not met. However, secondary outcomes suggest a need to further study the efficiency and efficacy of shorter consent forms for cancer clinical trial enrollment.
Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials
Guillermo Pechero Jr., Branden Pfaff, Mayank Rao, David Pogorzelski, Paula McKay, Ella Spicer, Andrea Howe, Haley K. Demyanovich, Debra L. Sietsema, Michael F. McTague, Lolita Ramsey, Martha Holden, Joshua Rudnicki, Jeff Wells, Michelle Medeiros, Gerard P. Slobogean, Sheila Sprague
Contemporary Clinical Trials Communications, 14 June 2021; 22
Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant’s before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent.
The PREP-IT program consists of two multi-center cluster randomized crossover trials that engaged patient advisors to determine an optimal model of consent. Patient advisors and stakeholders met regularly and reached consensus on decisions related to the trial design including the model for consent. Patient advisors provided valuable insight on how key decisions on trial design and conduct would be received by participants and the impact these decisions will have.
Patient advisors, together with stakeholders, reviewed the pros and cons and the requirements for the traditional model of consent, deferred consent, and waiver of consent. Collectively, they agreed upon a deferred consent model, in which patients may be approached for consent after their fracture surgery and prior to data collection. The consent rate in PREP-IT is 80.7%, and 0.67% of participants have withdrawn consent for participation.
Involvement of patient advisors in the development of an optimal model of consent has been successful. Engagement of patient advisors is recommended for other large trials where the traditional model of consent may not be optimal.
‘To say no wasn’t something we could do’; Reflexive accounts and negotiations of the ethical practice of informed consent during the research process and beyond [BOOK CHAPTER]
The Politics and Ethics of Representation in Qualitative Research, Routledge, 2021
In this chapter, the implementation of the formal ethical principle of informed consent in the research process is discussed. By analyzing encounters and exchanges with a young research participant, both during the fieldwork and after publication, the text examines the meaning of the concept of consent and discloses complexities and ambivalences inherent in asking for and giving consent. It shows that giving consent or ‘saying no’ is a complicated practice that should not be reduced to a single act or signature on a consent form. Rather, consenting to participate in research is an open-ended, situated, ambivalent and not necessarily verbal process. It might also have an impact on participants beyond the actual research process: for instance, when faced with the researcher’s representations of personal interview accounts in research reports. The text captures the relationality that exists between researchers and those we research, especially regarding how dependent researchers are on participants’ consent, their acts and the quality of the empirical material that participants ‘generate’.
Improving consent forms for first-in-human trials through participant feedback
Hannah Claire Sibold, Gavin Paul Campbell, John Bourgeois, Margie D. Dixon, R Donald Harvey, Rebecca D. Pentz
Journal of Clinical Oncology, 28 May 2021; 39(15)
Risks and benefits of investigational agents that have not been tested in humans are, at best, incompletely characterized in nonclinical investigations. Despite the growing emphasis to include patient voices in clinical trial design, no published research has explored patient preferences on how best to convey the information that the agent has not been tested in humans. This study established that First in Human (FIH) consent forms present this information in different locations and queried participants for their input on the preferable FIH consent form structure.
Consent forms for FIH oncology trials open to accrual at Winship Cancer Institute in 2019-2020 were analyzed for (1) the location of the mention that the study drug has not been used in humans before (FIH information), (2) the location of animal and other nonclinical data, and (3) placement of the risks section. Patients offered enrollment in a FIH trial were eligible for this study. Participants were interviewed during a clinic visit after consent was obtained. An ethics researcher asked questions about the participant’s opinions on the wording and placement of the FIH, nonclinical, and risk information in the specific trial consent form. All interviews were audio-recorded and double coded by two independent coders. The location of FIH and nonclinical data in the consent forms was compared to the patient’s suggested location for this information.
Saturation of themes was reached after interviewing 17 (17/19, 89% accrual) participants who were enrolled in 9 different FIH trials. Twenty FIH consents were qualitatively analyzed. Preferred placement compared to actual consent placement is listed in the table. 82% (14/17) of participants thought that nonclinical data on risks and efficacy was important to mention. 95% (19/20) of consents listed nonclinical data and most participants thought the placement in the consent was appropriate but 18% (3/17) of participants wanted the information earlier in the consent. No consent forms that were analyzed had the risks section before the study schedule; however, 47% (8/17) of participants wanted to move the risks sections before the study schedule.
There is considerable variation in the layout of FIH consent forms that does not align with patient preferences. Standardization of FIH consent forms to better reflect patient input is essential in order to promote understandability of these important yet sometimes misunderstood clinical trials and to ensure ethical informed consent.
Preparing accessible and understandable clinical research participant information leaflets and consent forms: a set of guidelines from an expert consensus conference
Eleanor Coleman, Lydia O’Sullivan, Rachel Crowley, Moira Hanbidge, Seán Driver, Thilo Kroll, Aoife Kelly, Alistair Nichol, Orlaith McCarthy, Prasanth Sukumar, Peter Doran
Research Involvement and Engagement, 18 May 2021; 7(31)
In line with Good Clinical Practice and the Declaration of Helsinki, it is the investigator’s responsibility to ensure that research participants are sufficiently informed, to enable the provision of informed consent. The Participant Information Leaflet/Informed Consent Form is key to facilitating this communication process. Although studies have indicated that clinical research Participant Information Leaflets/Informed Consent Forms are not optimal in terms of accessibility, there is little or no specific guidance available. The aim of this research was to propose and agree a set of guidelines for academic researchers and sponsors for preparing accessible and understandable Participant Information Leaflets/Informed Consent Forms.
A literature review identified guidance for the preparation of patient-facing documents. Following critical appraisal, key recommendations were extracted and a set of recommendations which can be applied to clinical research Participant Information Leaflets/Informed Consent Forms were prepared. These recommendations were evaluated and amended by an Expert Consensus Conference consisting of a group of key stakeholders. The stakeholders included members of a Research Ethics Committee (both lay and expert), a patient advocate, experienced clinical researchers, a plain English editor and a Data Protection Officer. Consensus was reached regarding a final set of recommendations.
44 recommendations were agreed upon and grouped into five categories: Layout, Formatting, Content, Language and Confirming Readability. These recommendations aimed to maximize accessibility for lay participants, including readers with dyslexia, literacy or numeracy challenges, thereby improving the quality of the consent process.
More empirical research is needed to further improve the informed consent process for research participants. However, these recommendations are informed by the current literature and have been ratified by expert stakeholders. It is hoped that these recommendations will help investigators and sponsors to consistently and efficiently produce more accessible clinical research Participant Information Leaflets/Informed Consent Forms.
Cross-sectional study on patients’ understanding and views on the informed consent procedure of a secondary stroke prevention trial
Felizitas A Eichner, Joschua M Reis, Joaquim Dores, Vladimir Pavlovic, Luisa Kreß, Naeimeh Daneshkhah, Renate Weinhardt, Armin Grau, Johannes Mühler, Hassan Soda, Christopher J Schwarzbach, Michael Schuler, Karl Georg Haeusler, Peter U Heuschmann
European Journal of Neurology, 14 May 2021
Improving understanding of study contents and procedures might enhance recruitment into studies and retention during follow-up. However, data in stroke patients on understanding of the informed consent (IC) procedure are sparse.
We conducted a cross-sectional study among ischemic stroke patients taking part in the IC procedure of an ongoing cluster-randomized secondary prevention trial. All aspects of the IC procedure were assessed in an interview using a standardized 20-item questionnaire. Responses were collected within 72 hours after the IC procedure and analyzed quantitatively and qualitatively. Participants were also asked regarding main reasons for participation.
146 stroke patients (65±12 years, 38% female) were enrolled. On average, patients recalled 66.4% (95% CI 65.2%-67.5%) of the content of the IC procedure. Most patients understood that participation was voluntary (99.3%) and that they had the right to withdraw consent (97.1%). 79.1% of the patients recalled the study duration, 56.1% the goal. Only 40.3% could clearly state a benefit of participation and 28.8% knew their group allocation. Younger age, higher graduation and allocation to the intervention group were associated with better understanding. Of all patients, 53% exclusively stated a personal, 22% an altruistic reason for participation.
While understanding of patient rights was high, many patients were unable to recall other important aspects of study content and procedures. Increased attention to older and less educated patients may help to enhance understanding in this patient population. Actual recruitment and retention benefit of an improved IC procedure remains to be tested in a randomized trial.
Leveraging Technology Solutions to Automate Informed Consent in a Clinical Research Hospital
Claribel L. Sawyerr
University of Maryland Baltimore, Doctor of Nursing Practice Projects, May 2021
Problem: Paper informed consent (PIC) forms are associated with incomplete and or inaccurate information such as missing signatures and incorrect patient identification. The Food and Drug Administration’s Bioresearch Monitoring Program audit for the 2019 fiscal year lists failure to obtain informed consent (IC) requirements as one of the most common violations (2%) by clinical investigators in clinical trials. In a selected practice site, approximately 440 (2%) out of 25,000 PICs were returned by the medical records department to clinicians in 2019 due to incomplete and or inaccurate information. This resulted in significant delays in the start of clinical trials, incurring additional time and effort for participants and clinicians to correct and or re-consent. Purpose: The purpose of this quality improvement project was to implement electronic informed consent (EIC) for research participants in the adult oncology, infectious disease, and digestive diseases outpatient clinics in a clinical research hospital. Methods: Pre and post implementation surveys were administered to clinicians (n = 43) to obtain baseline perceptions, and compare preferences and satisfaction with using PIC versus EIC. The clinicians were trained on using EIC for signatures, then EIC was implemented and tracked for eight specific protocol studies. Results: The average confirmed IC available in the electronic health record (EHR) within one day of signing by clinicians for all three clinics increased from 52.5% (pre) to 61.3% (post). EIC use increased by 20%, and returned consents decreased from an average of 2.2% to 0.6%. Clinician preference to use EIC over PIC increased from 44.8% to 57.1%, Fisher’s Exact Test = 0.5256, 2-sided, p > .05. Conclusions: Replacing PIC with EIC was preferred by clinicians, improved documentation of consent, and decreased the time for consent availability in the EHR. The implications for practice are that automating informed consent is associated with improved consenting processes and supports remote workflows.
Symptoms of Medication Withdrawal in Parkinson’s Disease: Considerations for Informed Consent in Patient-Oriented Research
Kaitlyn R. Hay, Neevi Kukreti, Paula Trujillo, Ya-Chen Lin, Hakmook Kang, Daniel O. Claassen
Pharmaceutical Medicine, 29 April 2021
Dopamine medication withdrawal in Parkinson’s disease (PD) is commonly employed in clinical practice and can be required for participation in research studies. When asked to withdraw from medications, participants often enquire as to what symptoms they should expect.
This study sought to improve the informed consent process by identifying patient-reported symptoms when dopamine treatment is withheld. We also sought to provide clinical guidance regarding the extent of these symptoms and consider participant willingness to undergo these assessments.
Participants were recruited from community-based PD programs and support groups in Nashville, Tennessee, USA. A patient-based questionnaire determined the frequency and severity of motor and nonmotor symptoms. The questionnaire also assessed whether patients would be willing to abstain from medication at a future date and under what circumstances.
A total of 31/90 participants reported willingness to withdraw from dopaminergic medications for clinical or research purposes. Tremor, walking, and balance were the most common motor symptoms that worsened during this time. Sleep dysfunction, constipation, and tremor were noted as the most severe symptoms. Of note, 10% of participants indicated that they would not be willing to go off medications again, suggesting that a minority of patients find this to be most discomforting. When prompted for a reason why participants would be willing to come off of their medications again, “for clinical purposes” was selected the most.
Study teams should list these symptoms in the applications to their institutional review board and in the informed consent to provide guidance for participants.
Rethinking consent processes for research in emergency departments
Joseph Miller, Stephen Guy Costa, David Alan Taylor, Paul Buntine
Emergency Medicine Australasia, 17 April 2021
Emergency medicine researchers face the challenge of prioritising patients’ immediate interests and maintaining hospital flow while attempting to collect clinical data. Even in low‐risk scenarios, excessive consent processes can make it difficult to recruit patients while observing guidelines on efficient triage. We discuss a recent situation in which a six‐page consent form appeared to deter clinicians from recruiting patients to a low‐risk intervention. We then argue that there need be no conflict between the imperatives of patient wellbeing and clinical research. Apparent conflicts between treatment and research could be reduced through creative recruitment techniques: the adoption of an ‘opt‐out’ approach; securing the budget for a dedicated research assistant; early consultation with the institution’s human research ethics committee; and the use of a short, simple participant information and consent form with a QR code linking to a more detailed outline of the study.
Transparency of informed consent in pilot and feasibility studies is inadequate: a single-center quality assurance study
Mohammed I.U. Khan, Lawrence Mbuagbaw, Matthew Holek, Faris Bdair, Zoha H. Durrani, Katie Mellor, Saskia Eddy, Sandra M. Eldridge, Claire L. Chan, Michael J. Campbell, Christine M. Bond, Sally Hopewell, Gillian A. Lancaster, Lehana Thabane
Pilot and Feasibility Studies, 16 April 2021; 7(96)
Pilot and feasibility studies (PAFS) often have complex objectives aimed at assessing feasibility of conducting a larger study. These may not be clear to participants in pilot studies.
Here, we aimed to assess the transparency of informed consent in PAFS by investigating whether researchers communicate, through patient information leaflets and consent forms, key features of the studies. We collected this data from original versions of these documents submitted for ethics approval and the final approved documents for PAFS submitted to the Hamilton Integrated Research Ethics Board, Canada.
One hundred eighty-four PAFS, submitted for ethics approval from 2004 to 2020, were included, and we found that of the approved consent documents which were provided to participants, 83.2% (153) stated the terms “pilot” or “feasibility” in their title, 12% (22) stated the definition of a pilot/feasibility study, 42.4% (78) of the studies stated their intent to assess feasibility, 19.6% (36) stated the specific feasibility objectives, 1.6% (3) stated the criteria for success of the pilot study, and 0.5% (1) stated all five of these criteria. After ethics review, a small increase in transparency occurred, ranging from 1.6 to 2.8% depending on the criteria. By extracting data from the protocols of the PAFS, we found that 73.9% (136) stated intent to assess feasibility, 71.2% (131) stated specific feasibility objectives, and 33.7% (62) stated criteria for success of the study to lead to a larger study.
The transparency of informed consent in PAFS is inadequate and needs to be specifically addressed by research ethics guidelines. Research ethics boards and researchers ought to be made aware and mindful of best practices of informed consent in the context of PAFS.