In clinical trials, participants receive several key documents to inform them about the study, their rights, and the procedures involved. These documents may include some or all of the following:

·       The Informed Consent Form (ICF)

·       Participant Information Sheet

·       Study Schedule and Visit Calendar

·       Patient Diary or Logbook

·       Emergency Contact Information and Safety Card

·       Withdrawal Form

·       Financial Information or Compensation Details

·       HIPAA Authorization Form (for trials based in the USA)

·       Study Drug Information Leaflet, and

·       Post-Study Follow-Up Information.

There are three key purposes to these documents:

·       to maintain ethical standards

·       to comply with local regulations

·        to empower participants to make informed decisions.

This article focuses on the Informed Consent Form (ICF) and the Participant Information Sheet (sometimes unfortunately abbreviated to ‘PIS’ and pronounced as a word, rather than an acronym…)

Informed consent is supposed to be a cornerstone of ethical clinical research. They are designed for participants to understand the purpose, procedures, risks, and benefits of a trial before deciding to participate in it. In addition to informed consent forms, assent forms are used for minors or individuals with limited decision-making capacity, and patient information sheets provide supplementary details to help potential participants make informed decisions.

However, all three patient-facing documents have posed significant challenges for patients. They are difficult to understand, often culturally relevant and these problems are pervasive. Whenever we encounter them, we wonder where they have come from. They just seem to appear: a document used over and over, part medical, part legal; Neither one thing or the other, like a zorse or a liger. What kind of alchemy has produced this document? Nobody can ever get to the bottom of their authorship. It must be a team made up of clinical, regulatory, legal and marketing personnel. They are hardly accessible. Seriously, who writes this stuff? These problems are magnified in international trials where the same documents are often used across diverse populations with different cultural norms, literacy levels, and healthcare systems.

This article explores the issues surrounding lay understanding of informed consent, assent, and patient information sheets, especially in global contexts, and suggests practical solutions to enhance comprehension and ethical decision-making.

Complex Language and Medical Jargon

Informed consent, assent, and patient information sheets are often filled with medical jargon, legal terminology, and complex language. Terms like "placebo," "randomisation," "adverse events," and "confidentiality" are confusing for lay people, particularly children or individuals with limited literacy. Also, legal and regulatory requirements contribute to the complexity, making these documents lengthy and difficult to navigate.

This has a real and immediate impact. Complex language leads to potential participants failing to understand important information about the trial’s purpose, procedures, risks, and benefits. These compromise informed consent, assent, and patient engagement. Participants may agree to procedures they do not fully understand.

Then, there is the international context. In global trials, the same documents are often used across culturally diverse sites without adequate localisation. For example, a patient information sheet designed for the United States may be used in Kenya or Nigeria without modification, despite significant differences in language, literacy, and cultural norms. For several decades, study after study have confirmed this as an urgent problem. Yet still the same one-size-fits-all information is used.

Information Overload and Length

Informed consent, assent, and patient information sheets are frequently lengthy and densely packed with exhaustive lists of potential side effects, legal disclaimers, and details of procedure. This information overload can overwhelm participants, leading to skimming or selective reading, especially if presented in an electronic format, which might encourage skipping through screens. This compromises informed consent, assent, and patient education, as individuals might make decisions without a full understanding of the implications.

In international trials, lengthy documents pose greater challenges in low- and middle-income countries where participants may have lower literacy levels or limited experience with formal documentation. Additionally, cultural norms in some regions favour oral communication, making lengthy written documents less effective.

Inadequate Explanation of Risks and Benefits

Consent forms, assent forms, and patient information sheets often use statistical terms or vague language to describe risks and benefits. Terms like "low risk" or "1 in 1,000 chance" may not resonate with laypersons, particularly children who may not have developed probabilistic thinking.

This means that misunderstanding risks and benefits can result in unrealistic expectations or fear-driven decisions. Participants may overestimate potential benefits or underestimate risks, leading to biased consent or assent.

In global trials, cultural differences in risk perception and health beliefs can influence how risks and benefits are interpreted. For example, communities with high levels of medical mistrust or different beliefs about illness causality may understand risks differently.

Ethical Implications and Global Standards

International clinical trials must adhere to ethical standards from regulatory bodies like the FDA, EMA, and WHO. However, inconsistent implementation and varying local regulations can impact informed consent, assent, and patient information sheet quality. Using standardised documents globally overlooks cultural and contextual differences, raising ethical concerns.

Conclusion

The challenges surrounding lay understanding of informed consent, assent, and patient information sheets are amplified in international trials. This is another area where patient engagement is not attended to. By simplifying language, localising documents, using multimedia tools, and enhancing cultural sensitivity, researchers can improve these practices worldwide.

Informed consent, assent, and patient information are not merely about obtaining signatures but ensuring that participants genuinely understand and agree to participate. As clinical research continues to globalise, adopting these best practices is essential to upholding ethical standards and promote equitable access to research participation.

Stakeholders, including researchers, ethics committees, and regulatory bodies, must be tougher. There needs to be a collaboration to design informed consent, assent, and patient information processes that prioritise comprehension, cultural sensitivity, and participant autonomy. By addressing these challenges, clinical research can advance ethically and inclusively across diverse populations worldwide.

Thank you for reading,

Mark Gibson

Sunderland, United Kingdom