Fifty-three recommendations were extracted and evaluated by the experts in this study. Most of the recommendations were considered “appropriate” and only a few changes were suggested. The modification of “appropriateness” to a more restrictive level resulted in a greater number of recommendations with the result "uncertain". This was very positive as it permitted a more fruitful discussion during the virtual meeting. It should be noted that on the original scale of appropriateness levels, all the recommendations evaluated would have been rated as "appropriate” after the two rounds.
The outcome of the virtual meeting was a better understanding of the panellists’ point of view, leading to the modification of some recommendations towards a more consensual content and wording. It was also an opportunity to explain the i-CONSENT rationale behind each recommendation, to clarify any doubts, and to allow all the experts to share their opinion on each recommendation. This approach benefitted the second-round evaluation, which better reflects the experts’ opinion.
The composition of the panel, with overrepresentation of patient representatives and women, was especially suitable for the objectives of the study, as two of the main objectives of the guidelines aim to put study participants in the centre of the process and to include a gender perspective. It is also important to note that most of the patient representatives were also investigators. Furthermore, due to COVID-19 pandemic, the in-person meeting was conducted remotely. The impact of these factors on the final results was thought to be low.
IC as a continuous communication process
The recommendation rated highest in the overall survey was to consider informed consent as a “two-way continuous communication process that begins at first contact with the potential participant and continues until the end of the study”.
The ICP described in the i-CONSENT guidelines is a five-step process (Fig. 3). During this process, continuous feedback and communication between the potential or current participant and the research team is essential.
This “first contact”, as described in the i-CONSENT guidelines, aims to raise awareness of the study and provide essential study information before the recruitment process begins.
The panellists found it appropriate to consider the use of different channels to advertise the study, including social media and websites, in addition to the traditional routes. Even so, they highlighted the need to consider aspects of digital poverty and how the use of these channels actively excludes some pockets of society. The experts were also very cautious about recommending the use of email to reach out to potential participants. Recommendation 13 was reformulated after discussion to add some clarification and to remove any mention of decentralized clinical trials.
It is important to note that the Heads of Medicines Agencies (HMA) and the European Medicines Agency (EMA) (12) highlight the importance of understanding the implications of recruiting patients to research via social media.
Panellists agreed to recommend the inclusion of the following information during this first contact:
- The purpose of the research, the importance of the study, and expected duration;
- The target population with some inclusion/exclusion criteria (e.g., pregnant women between 18–40 years old);
- A brief description of the relevant study procedures (e.g., a routine blood sample); and
- The contact person at the study site.
A recommendation to provide the potential participant with all relevant information about the study (step 2) before the discussion with the investigator (step 3) was also considered appropriate, in order to ensure that they have had sufficient time to think about it and to prepare any questions.
The discussion between the potential participant and the investigator is clearly seen as a fundamental step of the ICP. The i-CONSENT project, however, strongly recommends separating both events (information and dialogue) during the process, because some potential participants make the decision to participate based solely on this interaction, without fully reading the patient information sheet (PIS) to the end. Traceability of dialogue is very difficult, and it is impossible to guarantee that all relevant information about the study has been delivered during the discussion.
Furthermore, it was considered appropriate that the participant be assured access to the information used during the ICP and knows how to access it throughout the study and for the period established by law.
The panellists also agreed on the importance of obtaining participants’ feedback on the ICP but they were unsure about how to obtain it (how often, when, how). The i-CONSENT project advocates obtaining feedback from participants to make the ICP more dynamic and responsive over time, adjusting it to the needs and preferences of the participants. The i-CONSENT also highlights the use of feedback tools, such as the Study Participant Feedback Questionnaire Toolkit (13) developed by Transcelerate Biopharma. The i-CONSENT similarly recommends obtaining feedback at different moments during the study: after signing the consent, during the intervention, and at the end of the study. Although none of the panellists advised against obtaining feedback at these three timepoints, and the majority of panellists were in favour of the concept, there was no agreement on the appropriateness of this recommendation, since some respondents considered that this could overburden investigators and/or participants.
Health and digital literacy
Several studies identify health literacy as an important determinant of a patient’s capacity to provide fully informed consent (14, 15), and the i-CONSENT project sees the consent process as an opportunity to improve the health literacy of participants.
Panellists recognise the importance of health literacy but, in their opinion, it is not the duty of the research team to train participants in health and digital literacy or on how to detect fake news and unreliable sources. Some believed that these recommendations place an excessive burden on investigators.
Panellists believed that the emphasis should be on adapting the information to the target population’s preferences and needs, instead of adapting the population to the information. In this respect, one of the panellists stated: “I do not agree that the ICP should train participants in health literacy. The ambition for study teams MUST be to adjust information to the level(s) of participants, who might otherwise feel unsure or disrespected in their own right.”
Another idea highlighted by the panellists was the importance of creating information that does not require any further consultation, and that is easy for everyone to understand. In fact, there was no agreement on providing references or links to reliable sources of information.
Three recommendations considered appropriate by the panellists on this topic were to:
- Design the information to complete a possible lack of health literacy on the part of the potential participant.
- Use a glossary of terms to explain complex concepts.
- Use a layered approach for introducing study information, presenting the basic information in the general level and more specific messages in sub-layers. When using a document format (paper or pdf), these layers must be easily identifiable: the first layer will be in the main body and the sub-layers can come in a different format, such as in boxes or in different colours, or they can be presented in annexes.
Co-creation as a key idea
Co-creation was highlighted as a key intervention to increase the quality and understanding of the ICP, including the development of consent information. All panellists believed it was appropriate to recommend the “use of co-design as a central concept. Include participants during the design and review of the study information. Pre-test the information with representatives of the target population”. This is in line with the findings of a previous study conducted with representatives of patient groups in the framework of the i-CONSENT project (16).
Co-creation is important when producing a PIS, and it is equally important to summarize results, decision aids or any material about health information, such as information leaflets, in plain language. This took on particular importance when recommendation 23.2 was discussed: this recommendation was considered too weak because the recommendation to involve participants in the development and review of the summary was to be "considered" rather than a "must". Therefore, the recommendation was reformulated as "Involve participants in the development and review of the summary of results".
The panellists believe that it is appropriate to recommend co-design as a central concept and to use quantitative and qualitative interdisciplinary methodologies to involve and obtain insights from the target population. This strategy reinforces the proposal made by Jackson et al. to use a participatory and mixed methods approach to design informed consent in a way that best suits the needs of participants (17).
Tailoring the informed consent to potential participant preferences and needs
Usually during the ICP, patient information is only tailored to individual needs during in-person interactions. Normally, information materials are prepared without taking into account the preferences and needs of the target population.
Using a participatory and mixed method approach to develop informed consent will help identify the preferences and needs of the target population, including preferences regarding formats for presenting the information or the channels for contacting the research team.
Even so, as individual needs may differ from the general preferences of the target population, offering different possibilities during the ICP will help tailor it to the individual.
In this regard, most of the panellists felt that it was appropriate to offer potential participants a choice of more than one format for receiving information, and to provide different channels and formats for communicating with the research team.
As mentioned in the section on health and digital literacy, it is important to consider the benefit of presenting the information using a layered approach (especially if using a website). This approach will let the individual delve into the information they find most relevant or explore the explanations they need for better understanding.
Use of technical and methodological innovations
The use of digital technologies during the ICP is increasing. Several studies have measured the impact of interventions using multimedia, audio-video, or gamification to provide information to patients or potential participants (18, 19).
Most panellists considered it appropriate to recommend the use of technical and methodological innovations during the ICP to facilitate the participant experience, including the use of new technologies and formats to deliver information (hyperlinked website, video, storytelling, comics, mobile applications). It is important to note that the adequacy of this approach should always be taken into account from a social, methodological, legal, and ethical point of view.
Prepare inclusive information
According to the principle of justice and to ensure that the potential participant feels identified with the information provided, it is very important to prepare inclusive information and to implement an intercultural approach and a gender perspective.
The panellists believed that it is very appropriate to recommend procedures that incorporate a sensitive intercultural approach, empathizing with and being sensitive to the preferences and needs of people from different cultures, and adapting the consent process to their requirements as far as possible. Information should be provided in an easy-to-understand and culturally appropriate language and the participation of trained cross-cultural professionals in the study should be encouraged. It is also important to be aware that key concepts can be understood differently.
Literature on the gender perspective in the consent process is scant, and this is a controversial issue. Several studies exploring the ICP as a communication process have identified gender differences in this interaction. Even so, most authors agree that there are more common characteristics than differences, and that the differences identified are not categorical. Most studies that analysed differences in the understanding of informed consent in clinical trials by gender found no differences (4, 6, 20). Indeed, the few studies that identified differences mostly found a better understanding by women (21–24). Some studies also found that women were more inclined to read the entire PIS (25).
The panellists highlighted the importance of applying a gender perspective during the consent process, taking into account the influence of gender on health needs and concerns. This concern is in line with that expressed by the European Commission in the H2020 call “SwafS-17-2016 - The ethics of informed consent in novel treatment including a gender perspective”.
The consent process must be conducted without reinforcing stereotypes. Using one PIS for men and another for women in the same study is difficult to justify and unacceptable in most cases. The best way to adapt informed consent to the target population is to take that population into account when designing the information via a process of co-creation. Moreover, in-person discussion will be essential to adapt the consent process to the particular characteristics of the potential participant, connecting with the individual without making gender-based assumptions.
Two actions that seemed to be beneficial in applying a gender perspective, but that failed to achieve agreement during the study, were:
- When the study is directed at a single sex group, it can be useful to take into account communication and eye-tracking differences when designing the materials.
- In research of a more sensitive nature (e.g., trials of vaccines against sexually transmitted diseases) it may be beneficial if the investigator in contact with the potential participant is of the same sex.
Assessing understanding of information
Recommendations 18 and 29 highlighted the importance of the communication skills of the investigator. Panellists stated that the potential participant’s understanding has to be achieved through natural conversation. The experts were very critical of the use of questionnaires (especially with MacCAT) or the teach-back method. These, in their opinion, feel artificial and make the potential participant feel as if they are in an exam. Glaser et al. (19), however, highlight the positive impact of verbal discussion with test/feedback or teach-back components for improving patient comprehension. For this reason, we believe that while the best option is to have investigators with good communication skills that do not need to use these components, they can be a useful tool during verbal discussion at certain times.
Defining how to assess understanding is another important question that emerged during the discussion. The initial proposal for recommendation 18 was to verify that potential participants have understood “all” the information about the study, but this was considered unrealistic and unnecessary in most studies, and a more appropriate recommendation would be to verify that potential participants have understood “all relevant” information about the study. The information considered as relevant must be defined during the co-creation of the information, taking into account both perspectives (investigator/sponsor and potential participants).
In addition to providing clear and complete information, ensuring its understanding and replying to the doubts the potential participant, the panellists believe it is appropriate to recommend the use of decision-making tools to facilitate the process.
Participant involvement at the end of the study
Participants should be informed at the end of the study about the results, and they should also be included in the early phases of disseminating the results.
A “thank you letter” is a good way of thanking the participant for their participation in the study and, if possible, giving a preview of the results and instructions on how to access the summary of results when it is ready.
Providing a summary of results is considered appropriate for all studies, not only clinical trials; participants should be involved in producing and reviewing the summary (as mentioned above). Other formats, including written reports, may be considered for the summary and the one that best suits the characteristics of the target population must be selected.