Vulnerabilities of Cancer Patients and Their Effects on Informed Consent for Biobanking

Physical vulnerability

In the middle of a routine informed consent discussion, a patient with a brain tumor suffered from a sudden petit mal seizure. After a brief pause to ensure that the patient's spouse had a hold of the patient as a safety precaution, the coordinator hurried out of the room to retrieve the attending physician. With the physician's guidance, the patient was quickly stabilized, and soon after the patient safely returned to their senses. Surprisingly, the patient apologized, stated that this happens to them occasionally, and should not be cause for alarm. The patient, with the verbal support of their spouse, then insisted on continuing with the consent process. A bit shaken but still outwardly composed, the coordinator obtained the informed consent successfully, although with a newfound respect for the strength and resilience a patient can display despite their health related vulnerabilities.

The above experience provides insight into how a patient's physical vulnerabilities can complicate the informed consent process. A coordinator must be prepared for the unexpected and respond carefully as this situation can often lead to panic and exacerbate the issue even further. The key approach in handling this physical vulnerability was for the coordinator to remain calm and seek assistance from the health care provider in a potential emergency like the one described. The physical and psychological vulnerabilities caused by underlying diseases are an inherent but often overlooked burden on patients that can impact the consenting process. These vulnerabilities include but are not limited to loss of limb, tracheostomy-based speech loss, loss of eyesight, intense pain, mobility limitations, and loss of bodily control. ⁷ The patients that are adversely affected by physical vulnerabilities are a significant challenge to consent because a coordinator must be prepared for a patient's vulnerability to uniquely influence the discussion. These patients may require special assistance to provide them informed consent during a consent discussion such as holding materials required for the consent, reading the document aloud, or straining to listen to the patient due to their speech impediment. When special assistance cannot be reasonably provided, coordinators may handle these issues by providing a consent form for the patient to take home and review with the help of their trusted friends and family or by waiting for professional onsite physical aid from the health care provider or clinical staff for patients who require it.

Educational vulnerability

During a clinic visit, a patient diagnosed with head and neck cancer expressed interest in participating in research. During the informed consent discussion, it became apparent through the many stops and stutters in the conversation that the language and subject matter being presented by the coordinator about the study were not being understood by the patient. The patient did not understand the concept of specimen collection, processing, and the distribution of research samples in the research process and repeatedly questioned the meaning of the consent form. It was clear to the coordinator that the patient was not absorbing any of the content. In response, the coordinator simplified the wording of the consent form line by line and through the usage of colloquial metaphors such as “blood processing is like separating the laundry before the wash, if the colors are all mixed you won't get the result you want at the end.” Through this approach, the patient began to understand the true implications of the study. The coordinator allowed the patient time to think about their decision by advising the patient to not sign the consent form during the visit. The coordinator gave the patient a copy to review at home and scheduled another follow-up meeting with the patient at their next clinic visit to allow the patient to decide if they wanted to sign the consent form. The patient appeared at their next visit with a better understanding of the study and signed the consent.

The concept of biobanking is also not well understood by some patients and, in some cases, is mistaken with clinical trials. This can create additional confusion for patients that may result in their refusal to participate because patients already enrolled in clinical trials may not want to add more complexity to their treatment. To avoid this outcome, the coordinator has to concisely breakdown the differences between biobanking and clinical trial care with the patient before finalizing a discussion.

Patients have vastly different educational and socioeconomic backgrounds from one another, and a coordinator must be effective at navigating these differences while discussing biobanking during an informed consent discussion. In general, research is not well known for its concise and easily understandable written material. ⁸ According to the Department of Health and Human Services (HHS) guidance at 45 Code of Federal Regulations (CFR) 16.116 and Food and Drug Administration (FDA) regulations 21CFR 50.20,^9,10 it is required that consent language must be understandable to the participant. In addition, the IRB suggests that the investigators aim to write their informed consent forms and other research material at the 6–8 grade reading level to ensure broad patient understanding. However, even with these regulations consent forms often contain words unfamiliar to a layperson. This can present a challenge to most coordinators because not all patients coming into clinic will possess a sufficient educational background to understand medical or scientific language. Presenting unfamiliar concepts and scientific studies to patients who lack educational foundations in science and are stressed by their potentially life-threatening disease will certainly produce patient discomfort and risk uninformed patient enrollment. ³ This makes educationally vulnerable patients difficult to enroll in research in a manner that ensures that they are actually providing informed consent. The responsibility falls on the coordinator to notice the confusion evident in a conversation with a patient or the hesitation in a patient's responses regarding the informed consent material so that the coordinator can make a judgment whether the patient is providing uninformed or informed consent. The principle that holds researchers accountable for patient comprehension is established by the Belmont Report. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research established in this report that since “the subject's ability to understand is a function of intelligence, rationality, maturity and language, it is necessary to adapt the presentation of the information to the subject's capacities. Investigators are responsible for ascertaining that the subject has comprehended the information.” ¹¹ If a coordinator notices any lack of comprehension, it may be best to leave the consent documents with the patient and follow-up at another time, instead of closing the informed consent process with a signature or a patient decline.

Patients' educational background can also cause them to be naturally wary to concepts that they perceive as overly complex, even when they may not be in observable distress. To remedy this perception, the coordinator can approach the patient using anecdotes, easily understood metaphors, and colloquial language to provide a more relaxed conversational atmosphere as described in this encounter. However, it is important to balance the degree to which one changes their syntax and word choice to ensure that “talking down” to the patient is avoided. In the encounter, consent was not achieved on the first visit, as the full understanding of the project by the patient was in question. By simply scheduling a follow-up meeting with the patient, a coordinator can further probe a patient's understanding of a project through recitation and engaged questioning. This allows for an informed consent to develop gradually over time as the patient reaches a level of comprehension with the study that meets satisfactory informed consent requirements. This encounter can be expected by biobanks, because properly enrolling patients through informed consent is a process, not a one-time interaction, especially if the biobank allows patients to rescind their consent at any time.

Language-based vulnerabilities

While performing an informed consent with a Russian speaking patient using the UC San Diego Health approved online translator service, Martti (My Accessible Real-Time Trusted Interpreter), ¹² the coordinator and patient both stumbled into issues with time delays and malfunctioning of the service. Due to bad internet connections in the clinic room, neither the phone translator nor the Martti online translator service could connect to the network. At first, the patient was willing to wait, but the delay was over a half hour and internet connection still did not improve. This delay did not fit into the patient's treatment schedule, which resulted in the discussion being aborted.

This encounter portrays a patient that was impeded by a language barrier within the clinic, which is a form of language barrier vulnerability. One of the challenges that many medical and research communities face is effectively communicating with non-English patients. While clear communication should be a priority for all research coordinators, a language barrier between the patient and coordinator may cause confusion between both parties since neither may be able to directly express their confusion to one another. A 2007 study found that English-speaking patients were significantly more likely to be provided full documentation of informed consent for common invasive procedures than non-English speaking patients. ¹³ This can be attributed to the ease of providing English documentation and explanation for these procedures, something that non-English speaking patients do not receive equally. The gap of understanding between English-speaking patients and non-English speaking patients goes beyond the content of what is communicated. Indeed, compared to English-speaking patients, non-English speaking patients understand less of the surgical procedures and associated risks they are presented with during preoperative consent. ¹⁴ Reducing the language barriers that impede non-English speaking patients will help ensure that their informed consent enrollment is obtained. Furthermore, it will lead to an increase in the diversity of patients that participate in research as formerly unapproachable patient populations will become available through more robust inclusion efforts.

Medical interpreters and digital translators may be available to make sure that consent forms and medical care are delivered in an accurate and comprehensible manner. Despite the availability of these resources in hospitals, they may not be effective in easing communication between a non-English speaking patient and a provider. ¹³ Not only does a language barrier inhibit comprehension, it may also slow down or halt the informed consent process if a reliable translator is not present. When a coordinator and their patient are forced to rely on a secondary interpretation service, especially a technology based service that is vulnerable to factors such as connectivity, availability, and the time constraints of the translators, the consent process suffers greatly. The non-English speaking patients are burdened by the cumbersome interpretation process, which greatly delays a patient's appointment and may cause the consent process to become uncomfortable for many participants. It has been established by past studies that these burdens include “arrangement difficulties, availability and accessibility of interpreter services, convenience, confidentiality and privacy-related issues, and impact on the patient's comfort.” Highlighting this further, a study stated that: “availability of interpretation service is time-bound and we have to book the interpreter for an hour… also it is not convenient because they can only be arranged at certain times of the day.” ¹⁵ It is quite difficult to overcome the systemic vulnerability presented above; and even though an effective solution may be to hire a coordinator who spoke multiple languages fluently, this is unrealistic. However, a biobank may consider hiring personnel that speak the languages spoken by their patient population to alleviate the challenges presented by the interpreter's limited availability and the challenges of internet connectivity issues. This allows the conversation and communication to happen directly between the coordinator and the patient. It has been established that using a patient's preferred/native language creates a more comfortable environment for the patient and makes it easier for the patient to listen and comprehend. The comfort experienced by the patient when using their native language permeates multiple aspects of health care. Studies have “demonstrated improved attitudes and comfort levels toward end-of-life discussions of Latinos when counseled by a specially-trained staff member using the patients' preferred language.” ^16,17 It is also important to point out that the manner in which a native language is spoken to a patient is critical to their comfort and understanding. With that in mind, digital interpretation by an interpreter on a video screen creates a unique obstacle to informed consent because of the lack of personal connection. If the interpreter speaks with a higher level vocabulary than the patient in their native language or the interpreter misunderstands the coordinators phrasing, then the digital interpreter becomes a detriment to the consent process. However, when a coordinator speaks the patient's language, these issues can be discussed between the patient and the coordinator to alleviate some of the strain that the patient may experience during informed consent.

Cognitive vulnerability

A patient with an undiagnosed mental condition that did not appear in their medical record at the time of prescreening was approached for consent. The patient appeared to understand the content of the informed consent and agreed to sign where the coordinator indicated. They nodded along during the consent process as if understanding; however, once the coordinator asked the patient to sign the last page, the patient was suddenly perplexed about the meaning of the document. The patient then stated that they would need to make sure that their spouse would be okay with them participating in the biobanking study. The patient moved on to tell stories about how their spouse would plow the field and harvest their crops. The patient's son was present and reminded the patient that their spouse had passed away. Then the patient looked at the coordinator blankly and asked what document they were signing. The coordinator hesitantly explained again, but the patient repeated that they wanted to confirm with their spouse before continuing and then refused to cooperate any further. At this point, it became clear to the coordinator that the prescreening process had failed, and the patient did not meet the criteria in the BR IRB-approved protocol to provide informed consent because of a cognitive vulnerability that the coordinator was unaware of and did not feel comfortable navigating. The coordinator then terminated the discussion.

Another challenge that coordinators must navigate are cognitive vulnerabilities among the patient population, as seen in the above encounter. Types of cognitive vulnerability can be defined as learning disabilities to more severe types of diseases such as Alzheimer's, schizophrenia, etc. ¹⁸ The patient in the above encounter was referred to MCC from another institution, and after careful investigation by the coordinator, it was discovered that the patient was previously diagnosed with schizophrenia, even though diagnosis was not documented in the medical record that the coordinator had previously screened. Psychiatric illnesses jeopardize the informed consent process as they often make the patient incapable of comprehending their rights during an informed consent encounter, thus causing an uninformed enrollment to occur if the patient agrees without legal oversight. In these scenarios, as per the principle of “Respect for Persons,” when a patient has a diminished capability to comprehend and deliberate information they are entitled to protection that stems from a third party. This third party entity has full comprehension of the participant's vulnerabilities and acts with their best interests in mind while aiding in the decision making process. ¹¹ While “informed consent can also be obtained from a [legally authorized representative (LAR)] to make treatment decisions for the patient,” ¹⁸ the patient often does not have a LAR present in clinic, and the consent discussion becomes difficult to perform if the patient's cognitive vulnerability disables their comprehension. Cognitive vulnerability becomes a barrier to enrolling new patients when the patient's medical history does not reflect their current condition, as these vulnerable patients may be accidentally flagged as eligible for research by the coordinator, who is unaware of the patient's condition. Oftentimes, physicians reach a conclusion about a patient's ability to understand the wording of a consent after they have consented them for surgery.^18,19 This is an issue not only for physicians but also for biobanking researchers because if a patient does not comprehend a consent discussion then informed consent is not obtained.

Experiential vulnerability

During an informed consent with a patient with advanced squamous cell carcinoma, the coordinator began to introduce the study and the potential benefits that it could provide for future patients when the patient suddenly cut the coordinator off mid sentence and started crying. Through sobs the patient declared that no physician or researcher was able to help their spouse who had succumbed to cancer at UC San Diego only a few weeks ago. The patient continued in distress and denounced the promises made by their spouse's health care provider and questioned the motivations of all staff at UC San Diego. As this situation unfolded the coordinator listened respectfully, only breaking eye contact with the patient to note that the patient's family was also visibly upset. Once the patient calmed down, the coordinator addressed the room sympathetically, carefully avoiding the temptation to make an empty apology on behalf of the health care provider. The coordinator then sat down next to the patient and asked if they wanted to continue listening about the study since it might help other patients in the future. The patient nodded and, by the end of the discussion, had fully reverted to a calm demeanor and expressed the desire to be given time to think over the information presented. The coordinator expressed thanks for the patient's time, but before the coordinator left the room, the patient apologized for blaming the coordinator for the unfortunate loss of their spouse. The patient signed the informed consent on the next follow-up appointment.

The encounter above provides an example of how negative experiences in the health care system perceived by the patient can lead to the development of experiential vulnerabilities, which may prevent the patient from giving their consent to research. The first time a patient comes in to discussion with their physician, it is common for them to be easily overwhelmed by the complexities at clinic. From check in to check out, patients are exposed to a wide variety of clerical, clinical, and research staff, so much so that the distinction between the health care provider and research team may be misunderstood in the process. A patient's negative experiences with the health care system can often lead to mistrust in physicians, ²⁰ and this mistrust can easily be translated to research staff, leading to unwillingness to participate in research, as demonstrated in this encounter.

Furthermore, when the distinction between research and health care providers is misunderstood during a discussion, many patients can become concerned about adding an unfamiliar element to their treatment plan. It is imperative for a coordinator to make it clear to the patient that a protocol either has a direct effect on a patient's treatment, as is the case with clinical trials, or the study has no significant effect on a patient's care and health. These particular studies are labeled by an IRB as a minimal risk study as defined in federal regulations at 45 CFR 46.102(i) and 21 CFR 50.3(k). A coordinator's reiteration of the minimally invasive nature of a study during the consenting process is essential to get that message across, ²¹ especially for studies that do not contribute to patient care. These studies are often viewed as potential treatment “sale pitches” if a coordinator does not immediately state otherwise during a discussion. It is also recommended that a coordinator clearly states the sections of the informed consent that apply directly to the patient, especially if these are covered in the written consent form. This is due to the recurring observation that new patients can be bogged down early in a discussion if they are given all the minutia of the study first. This diverts them from fully understanding the information presented later about their privacy, care, and clinical experience going forward if they participate. It is important to be aware of the experiential vulnerabilities a new patient's status implies if a coordinator wants to maximize their effectiveness in clinic and minimize the unintentional stress they may place on these new patients.

Emotional vulnerability

A coordinator approached a patient diagnosed with laryngeal cancer. The patient verbally acknowledged being new to the clinic and asked how participating in research may affect their care. The coordinator then guided the patient through the informed consent and answered all of their questions. After this presentation, the patient's spouse encouraged the patient to consent, going so far as to say that they would consent if their roles were reversed. The patient, however, became even more wary of participating in research and expressed their wish to be left alone due to the complex treatment schedule they were just presented with moments before. The patient went on to explain that they did not want to schedule even more appointments just to participate in research, and although the coordinator attempted to explain how that would not be the case, the patient disagreed. The coordinator left the patient with a consent form and asked if the patient would be open to another approach in the future. The patient agreed, but on a follow-up discussion, the patient still declined consent and expressed how exhausted they were from the hectic treatment plan they had to follow.

Many patients are susceptible to emotional vulnerabilities during a discussion, as depicted in this encounter. These emotional stressors come from many different factors, including but not limited to fear, emotional fatigue, grief, denial, and pain. ³ Individuals who perform informed consent with patients of any background will have to learn to navigate delicate emotional situations to avoid adding to patients' stress or anxiety from lack of tact and compassion during a discussion. Emotionally distressed patients can offer some of the most poignant interviews if the coordinator can set aside some of their own time and share their sympathy with these patients. The patient's desire for care and sympathy should be addressed at the beginning of the informed consent process when the patient presents as outwardly distressed. Emotional responses are to be expected from patients and are entirely logical responses during a discussion. Therefore, a coordinator should sympathetically support the patient during these stressful situations and avoid being or seeming callous during these encounters. A coordinator must be careful to remain focused on their ethical duty to help patients with the limited mental and emotional support they can provide during a discussion, even though they are on the “research side” of the clinic. The distinction between health care providers and research teams should not encourage a detached callous approach to patient discussions, since it is the prerogative of all staff to increase the patients' quality of life and not inflict undue burden on them if possible.