Этические барьеры и адаптация протоколов: новые стандарты ухода за терминально больными в клинических исследованиях

The Art And Skill Of Caring For Terminally Ill Patients In Clinical Research And Beyond By Kamila Novak, KAN Consulting One day, every one of us will need to communicate with terminally ill people. It may be part of our profession in clinical research or as volunteers, caregivers, home nurses, or family members. Before leaving, terminally ill people typically enter something I call a transition chamber. Imagine a spaceship. It has an internal environment where the astronauts live, work, and rest. Sometimes, they have tasks in the open space requiring them to exit the spaceship. They cannot do it instantly. They need to get ready to go out and return in, and for this, they use the transition chamber called airlock, a sealed compartment with two airtight doors that allow crew members to move between the pressurized interior and the vacuum of outer space while minimizing the loss of cabin air. Often, a terminally ill person slowly loses interest in this world; they do not want to listen to the news, be told about the latest political or cultural events, or hear news in their former profession. Certain medications may also affect their ability to process information and understand a conversation. And losing control of their lives and abilities to care for themselves is very difficult. Of course, every person is different, and this means that there are no universal ways to approach an end-of-life situation. How we see terminally ill people, treat them, and talk to them matters immensely. We can spark their day with true attention and kindness or make it more difficult by saying things that sound like platitudes. We may have the best intentions, but what we say and what the person hears is not always the same. What You Say Matters — A Lot Imagine that you work in a hospital or a palliative care facility. You enter the patient’s room early in the morning with a loud, cheerful, “Good morning! How are you today?” The person was resting until you entered. They are unwell. Body functions are shutting down, they may be in pain, and they could have had a sleepless night. Do you really want them to draw their first attention to how they feel? In parts of the world, including the United Kingdom, this is a social phrase, and the last thing the person saying it expects is you to start telling them how you feel. Try it, and you will see an expression of surprise and almost visible thought on their face: “Why on Earth is he/she telling me this?” You are expected to smile and return the question without expecting any answer. The patient you greeted with this question is likely to hear it many times during the day from doctors, nurses, and visitors. It becomes meaningless and irritating. The same goes for phrases like: “You look better today!” “I know how you feel.” “How are we doing?” “You are strong.” “Do not give up. Keep fighting. Better days will come.” If you truly want to know how the person feels and show genuine care, ask these questions instead: “Do you have pain?” “How was your night?” “Is there something I can help you with?” There is a caveat: In some cultures, people may be happy to hear those typical phrases mentioned earlier. They wish to hear they look better and they will recover soon even if, deep inside, they know it is not true. So, knowing the person and their preferences is vital. Challenges To Providing Authentic Care The biggest challenge is usually the time pressure. Healthcare personnel face administrative tasks, documentation requirements for both medical care and reimbursement, limited headcount, and other demands. Spending time with patients has become a luxury at most institutions. Often, the time crunch results in a depersonalized environment where patients feel more like objects of standardized care not people with unique needs. In some countries, personalized care is expected to be provided by family members and personal nurses or caregivers. While that has some advantages, such as knowing the patient, it is not a solution for those who do not have anyone to stay with them. Keep in mind that cognitive decline may also accompany the last stages of life. Patients may find it difficult to follow conversations or understand questions. Even if they do follow and understand, they may need more time to respond, and due to the time limitations mentioned above, the doctor or a nurse may be gone before they can answer or ask a question. Additionally, patients may also lose their voice, speak like robots due to physical changes, and slur their speech. Understanding their words becomes difficult, which leads to frustration on both sides. Finally, patients close to the end of life may have vivid dreams and dream-like moments in reality and cannot determine what is what. What they say can include both and produce confusion. How Clinical Research Professionals Can Help Research involving terminally ill patients focuses on improving end-of-life quality, testing late-stage interventions, and understanding the dying process. Studies include clinical trials, qualitative interviews, and observational designs tailored to protect very vulnerable participants while addressing their physical, psychological, and spiritual needs. Study Types That Support End-of-Life Care - Palliative and Symptom Management Trials: These are quantitative studies testing medications or therapies to control pain, nausea, breathlessness, and fatigue without focusing on a cure. - Qualitative and Interview-Based Studies: These include exploratory research using open-ended questions to understand patient coping, preferences for care, and family communication. - Observational and Phenomenological Studies: They track natural disease trajectories, including phenomena like terminal lucidity or end-of-life dreams and visions. - Health Services and Quality Improvement: These studies evaluate hospice structures, home-care barriers, and decision-making frameworks to optimize health policies. - Phase 1/2 Oncology or Pharmacology Trials: Typically, they are innovative or high-risk therapeutic trials offering last-line experimental drug access when standard treatments fail. - Narrative Research: It analyzes patient and caregiver storytelling to map emotional, spiritual, and physical needs near the end of life. All these studies should uphold high ethical standards, follow scientifically valid protocols approved by IRBs/IECs, be tailored to the participant population, not impose unnecessary burden, and use fit-for-purpose data collection tools. Informed Consent Participant information and informed consent documents (ICDs) should be written in such a way that terminally ill people can follow and understand them. The FDA’s draft guidance “Key Information and Facilitating Understanding in Informed Consent”1 can provide valuable tips to make ICDs short, include visuals, and easier to understand. In addition, IRBs may have additional requirements for this specific vulnerable population, such as presence of a witness or a caregiver. No coercion and no incentivization standards apply, as in all research studies. We need to remember that coercion and incentives are not only the real ones but also those perceived. There are three main challenges related to ICDs: threats to voluntariness, measures to safeguard voluntariness, and questionable exclusion of certain groups.2 Recruitment Recruiting terminally ill patients for clinical and palliative studies involves navigating severe physical decline, rapid disease progression, emotional distress, and strict ethical requirements. These factors frequently delay study completion and cause lower participation rates. Patient and illness factors include things like: - High symptom burden - Worsening symptoms: Extreme fatigue, pain, or functional decline make participation physically exhausting. - Rapid deterioration: Sudden health crises or death can lead to high attrition before or during the trial. - Cognitive impairment: Delirium, dementia, or medication side effects frequently cause patients to lose the capacity to consent, complete visits, and respond to questionnaires. - Gatekeeping and provider barriers - Protective clinicians: Doctors and nurses often gatekeep by refusing to refer patients, wishing to shield them from extra stress. - Prognostic uncertainty: Accurately predicting a tight life expectancy window required by specific protocols is notoriously difficult. - Stigma and fear: Misconceptions about palliative care or research cause patients and families to reject enrollment. - Ethical and consent challenges - Threats to voluntariness: Vulnerable patients may feel pressured to join out of a false hope for therapeutic benefit. - Emotional distress: Initiating difficult end-of-life or prognostic discussions can cause anxiety for both patients and grieving family and caregivers. - Proxy consent dilemmas: Relying on family members to consent adds complex emotional and legal burdens. Procedures Study procedures should be as easy to do as possible. Ideally, include nothing invasive unless it is a Phase 1 study. We need to remember that the condition of terminally ill patients may deteriorate fast, and what was manageable in the beginning could become too much. Plan more or more demanding procedures (including longer questionnaires) in the beginning of the study and ease them toward the end. Protocol Deviations Protocol deviations are more likely to occur in studies with terminally ill people than in other studies. A procedure (including completion of a questionnaire) may be skipped or delayed as the participant gets too ill. This might be prevented by expecting deterioration and establishing a more patient-friendly schedule of events. Most of the time, numerous deviations are not a sign of a poor site performance but rather a sign of participants’ decline. As in any study, deviations should be meticulously recorded, assessed for importance, and reported per local regulatory and IRB requirements. Missing Data and Confounders We always wish to collect reliable, trustworthy data to analyze study results and make conclusions. This can be challenging in our study population of terminally ill participants. Missed procedures result in missing data, and changing states of consciousness and perception can produce incoherent data. The theory of estimands elaborated in ICH E9 (R1)3 can help predict them and determine suitable statistical methods to handle them. An experienced biostatistician should be part of the study team from the start. Remote Communication During the COVID-19 pandemic, we learned to communicate and work remotely, including telemedicine and remote psychological support. The remote modality offers both advantages and limitations. Advantages include the ease of reach. It is invaluable in moments of crises, and it overcomes physical limitations when patients become too weak. However, limitations include the lack of visual clues (we typically see the face, not the whole person and their body language) and the inability to provide comfort by touch. Success requires speaking slowly, embracing silence, asking permission before hard topics, and focusing heavily on emotional support since physical touch is impossible. Setting up technology matters. We should pick simple apps or devices that fit the person's technological skills. It is good to set a fixed daily or weekly routine for calls, so the person knows when to expect them. We can ask a local caregiver or nurse to help test the audio and video first and assist with opening the call. Final Tips For All — No Matter Your Role - Find time to get familiar with the person. The better we know them, the better we interpret their expression and behaviors, and the more we are sensitive to their changes. - Do not rush. The pace of terminally ill people, including thinking and processing information, is slowing down. Many questions asked one after the other may be confusing and overwhelming. - Do not underestimate nonverbal communication. Holding the person’s hand, moisturizing dry lips, or a gentle caress can say more than dozens of words. - Treat them with dignity as adults, not like children. - Respect them, their mood, and personal space. Be sure they agree before hugging or kissing them. - Offer help but do not force it. Let them choose. - For remote communication, speak slowly, use clear words, ask permission to discuss heavy subjects, express care, invite family or caregivers, say goodbye softly, and follow official guidance from groups like the Cancer Support Community for long-distance care management.4 Communicating with and caring for terminally ill patients is both an art and skill we should hone and keep improving. It is the balance of “not too much” and “not too little,” respecting their human dignity, needs, and wishes. References: - Key Information and Facilitating Understanding in Informed Consent, draft guidance, FDA, 2024. https://www.fda.gov/media/176663/download - Godskesen T, Björk J, Juth N. Challenges regarding informed consent in recruitment to clinical research: a qualitative study of clinical research nurses' experiences. Trials. 2023 Dec 11;24(1):801. doi: 10.1186/s13063-023-07844-6. PMID: 38082434; PMCID: PMC10712041. - ICH E9 (R1) Addendum, 2019. https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf - 4 Five Tips for Long-Distance Cancer Caregivers. https://www.cancersupportcommunity.org/blog/support-distance-5-tips-long-distance-caregivers About The Author: Kamila Novak, MSc, has been involved in clinical research since 1995, having worked in various positions in pharma and CROs. Since 2010, she has run her consulting company, focusing mostly on GXP auditing. She has firsthand experience with countries in Europe, the Middle East, Africa, and North America. Kamila chairs the DIA Clinical Research, Compliance & Quality Community and the SQA Data Integrity Subcommittee, leads the DIA Working Group on System Validation, and serves as a mentor at the SQA and the DIA. In addition, Kamila is a member of the CDISC, the European Medical Writers’ Association, the Florence Healthcare Site Enablement League, the Continuing Professional Development UK, and other professional organizations. She publishes articles and speaks at webinars and conferences. She received the SQA Distinguished Speaker Award in 2023 – 2025, the SQA Distinguished Mentor Award in 2025, and the DIA Global Inspire Award for Community Engagement in 2024. She and her company actively support capacity-building programs in Africa.