Same-Day Consent for Regional Anesthesia Clinical Research Trials: It’s About Time

Abstract

Coronavirus disease 2019 (COVID-19) has changed the way anesthesiologists engage and interact with patients. As we hopefully approach the backend of this crisis, plans for the resumption of “nonessential” anesthesia services, including providing anesthesia for elective surgeries, reopening of anesthesia preoperative assessment clinics (PAC), and recruiting for regional anesthesia clinical research trials, will take shape. The COVID-19 pandemic has, however, highlighted a significant challenge in the current approach to research and the advancement of scientific knowledge in the regional anesthesia field: the perceived need to obtain consent to participate in such research in advance of the actual day of surgery. Notwithstanding the low-risk nature of participation in most regional anesthesia clinical trials, subject recruitment on the same day as surgery is often prohibited by local research ethics boards (REB) due to their concerns regarding patient autonomy and perceptions of patient vulnerability immediately before surgery that could impact the voluntary nature and the rigor of the informed consent process. In many centers, the anesthesia PAC has long served as the sole permissible and fertile ground for subject recruitment to clinical research, presumably ensuring fully informed consent to participate in a clinical trial in the absence of any undue duress and facilitating the establishment of a mutually trustful relationship. With the COVID-19–related suspension of in-person assessments in anesthesia PACs across most academic centers, recruitment for ongoing regional anesthesia clinical research trials has come to an abrupt halt and brought the long-standing controversy of same-day informed consent for low-risk clinical trials squarely back to the fore. The widespread REB concerns regarding same-day informed consent for participation in regional anesthesia research trials have not been supported in the current literature. Even though anxiety in the face of impending surgery is a normal human reaction, patients are still presumed to be capable to continue to consent or to revoke consent to surgery while they wait to enter the operating room. There is no evidence that carefully conducted assessments of capacity to understand information pertaining to a research study and to appreciate how a choice to participate or not would apply to them cannot be performed in this period. There is no existing literature to suggest that patients are so vulnerable during this period that they must be systematically protected by prohibiting any discussion of potential participation in research in the immediate preoperative period. Arguably, such a systematic prohibition is ethically problematic in that, on its face, it appears paternalistic and can deny patients the benefits of research participation. The anticipation of a second wave of COVID-19 and the high likelihood of future pandemics from other emerging pathogens requires a more rigorous examination of such REB assumptions as prohibiting same-day consent to participate in regional anesthesia research risks stymying research and growth of this important and innovative field and fail in its goal to benefit patients in the perioperative period. ETHICAL TENETS AND INTERNATIONAL GUIDELINES The 1964 Declaration of Helsinki outlined the tenets of informed consent: competency, disclosure, autonomy.1 To ensure autonomy, subjects must offer their participation voluntarily, specifically, without any element of force, fraud, deceit, duress, or coercion. These tenets remain the pillars on which clinical research involving humans is founded and inform the respective Canadian and American Anesthesiologists’ Society’s guidelines for the ethical consult of clinical research.2,3 Despite adaptations and updates over several decades, a single truth has prevailed: consent is paramount and, as with treatment, no research can occur without consent. Chief among the roles of REBs is to ensure the consent process is rigorous and the autonomy of clinical research participants is respected. While the meaning of consent is both uniform and clear, that is, research participants must be capable of decision-making, fully informed, with ample time for consideration of options without coercion, and their choice must be respected,1 what constitutes ample time is not as clearly defined. The World Health Organization states that “subjects must be given ample opportunity to enquire about the details of the trial… sufficient time, determined by the patient’s health condition.”4 The Tri-Council Policy Statement, representing Canadian standards for ethical research involving humans, declares that “for consent to be informed, prospective participants shall be given adequate time and opportunity to assimilate the information provided.”5 In the United States, the American Medical Association is even less explicit, stating only that a valid consent process includes, “reviewing the process and any materials to ensure that it is understandable to the study population.”6 Locally, the University of Toronto’s position on “ample time” is equally vague, only to consider “whether the contact person is known to the subject/authorized third party, has access to the patient information as part of their normal professional duties, or is able to assess capacity to consent.”7 While there is currently no uniform explicit recommendation or absolute quantification for what constitutes adequate time for patient reflection before consenting to participate in a clinical research trial,4,5,7 hospital-based REBs are also given some guidance regarding how much time is inadequate. Specifically, the Canadian National Council on Bioethics in Human Research likens the practice of same-day consent to intimidation, coercion, and breach of autonomy.8 Ostensibly equating quantity with quality, some REBs have strongly discouraged same-day consent practices, instead opting for a minimum of 1–2 weeks for patient contemplation, irrespective of risk involved in study participation. Outside of North America, guidelines and recommendations on consenting practices for clinical research trials are similarly varied. The Table summarizes available recommendations from various international professional societies and government agencies regarding consent practices in the context of clinical research. Recommendations range from the oft-repeated requirement for “adequate” or “sufficient” time9,10,13 to a more explicit demand for at least 24 hours for patient consideration.11 A notable deviation is the proportionate approach to seeking consent for clinical trials advised by United Kingdom’s National Health Service (NHS).14 When seeking consent for patient participation in a clinical trial, the NHS recommends that “for research involving only minimal risks and/or little deviation from normal/standard clinical practice… it may be reasonable to accept a decision taken at the time of approach.”14 Additionally, the extent of information provided ought to be proportionate to the “nature and complexity of the research trial, risks, burdens, and potential benefits, the ethical issues at stake.”14 Table. - International Recommendations for Same-Day Consent Practices Country Institution Guidelines/Recommendations on Timing of Consent Specifications for Low-Risk Trials Australia National Health and Medical Research Council (2018)9 “Adequate time should be allowed for prospective participants to understand and consider what is proposed and for their questions and expression of concerns to be addressed by those obtaining their consent.” “Proportionate to needs of participants, study risks, and ethical sensitivity.” Belgium European Patient Forum (2016)10 “The patient must be given sufficient time to consider the decision.” “A common problem for patients is that they are often given too much information at once … it does not contribute to their understanding … or help in balancing the risks and benefits involved. Thus, a more flexible and tailored approach should be applied that allows individual needs to be met.” Denmark National Videnskabsetisk Komité (2011)11 “The time for reflection depends on the nature of the trial. Basically, it should be at least 24 h.” “The time for reflection depends on the nature of the trial.” France European Patient Forum (2016)10 “The patient must be given sufficient time to consider the decision.” “A common problem for patients is that they are often given too much information at once … it does not contribute to their understanding … or help in balancing the risks and benefits involved. Thus, a more flexible and tailored approach should be applied that allows individual needs to be met.” Ireland Health Service Executive: Quality and Patient Safety Division (2013)12 “It is good practice where possible to seek the service user’s consent to the proposed procedure well in advance, when there is time to respond to the service user’s questions and provide adequate information.” “Where the research poses more than minimal risk, it should … offer the prospect of direct benefits for the participants themselves and be commensurate with the level of foreseeable risk.” “Asking a service user to provide consent just before the procedure is due to start, at a time when they may be feeling particularly vulnerable, or seeking consent from someone who is sedated, in pain or anxious, creates doubt as to the validity of the consent.” “Where the research entails only minimal risk, it is sufficient if the research offers the prospect of benefits either to the participants directly or to the group which is the focus of the research and to which the participants belong.” New Zealand Auckland District Health Board (2018)13 “Sufficient time should be allowed for the patient to read the written information, and discuss this and any verbal information with whomever they wish.” “The higher the probability of risk or the greater the magnitude of harm, the more care and detail in giving information is required.” “The patient must be informed of rare risks that are more likely because of their particular circumstances, or which would have greater significance for that particular patient, for example, the consequences of arm nerve damage for a carpenter.” United Kingdom NHS Health Research Authority (2019)14 “There are no definitive guidelines or legislation regarding the appropriate amount of time (or minimum amount of time) that potential participants should be allowed to consider whether to take part in research or not. A proportionate approach (in a nonurgent scenario) means that for more complex or burdensome studies a longer time may need to be provided for potential participants to consider their decision than that provided for simpler studies involving lower risks…For research involving only minimal risks…it may be reasonable to accept a decision taken at the time of approach.” “A proportionate approach to seeking consent, that is, adopting procedures commensurate with the balance of risk and benefits, should always be adopted so that potential participants are not overwhelmed by unnecessarily lengthy, complex, and inaccessible information sheets but instead are provided with succinct, relevant, truthful information in a user-friendly manner that better promotes their autonomy.” “The methods and procedures used to seek informed consent and the level of information provided should be proportionate to: -Nature and complexity of the research -Risks, burdens, and potential benefits -Ethical issues at stake” Abbreviation: NHS, National Health Service. Most physicians and surgeons meet with their patients on multiple occasions, affording these investigators time to identify, recruit, and enroll suitable research participants and obtain informed consent. However, specialties, such as anesthesiology, critical care, interventional radiology, and emergency medicine, have a varied pattern of practice and patient acquaintance that does not typically afford the luxury of time or, in many cases, delayed consent to research.15 Indeed, the initial encounter between anesthesiologists and patients undergoing elective procedures routinely occurs on the day of surgery. Recognizing our specialty’s unique practice patterns, the Canadian Anesthesiologists’ Society’s guidelines on the ethics of clinical research state that “preoperative consent for clinical research in anesthesia may be obtained after admission to hospital, either before or on the day of the scheduled surgery.”2 Yet an impasse is occurring in regional anesthesia with clinical investigators working in a time-limited perioperative system yet prohibited by REBs, both locally and otherwise, from consenting patients for clinical trials on the same day as surgery.8,15 THE QUESTION OF PATIENT VULNERABILITY AND NEED FOR PROTECTION IN PRACTICE Concerns of inadequate patient comprehension, time for contemplation, and privacy, as well as undue duress, coercion, and anxiety, continue to undermine same-day consent for regional anesthesia clinical research trials. These concerns, however, have not been borne out in the literature. When consent is obtained on the same day as surgery, the vast majority of patients do understand the intent of the clinical anesthesia trials and recognize that participation is voluntary and that consent may be withdrawn at any time without consequence.16,17 Patients are capable of digesting consent form documents and making informed decisions about research participation in thirty minutes or less.16,18 Similarly, most patients feel that the perioperative setting offers adequate privacy for consent discussions.16 Purported coercion of patients by their clinician investigators in the immediate preoperative setting has also been refuted16,17; 1 anesthesia study found that 97% of patients rated the preoperative setting as “ideal” for obtaining informed consent to participate in clinical anesthesia trials.16 The latter is most likely explained by patient preference for physicians with whom they will and/or must establish a relationship; accordingly, same-day consent by the responsible physician is likely superior to that by any surrogate.18 Moreover, concerns of patient anxiety have not been realized as anesthesia researchers found no incremental increase in patient anxiety with same-day versus day-before recruitment and consent.19 Finally, increasing the quantity of time for patient contemplation as a means to increase the quality of the informed consent process for regional anesthesia research has not been substantiated.20 Moreover, nowhere in medicine is the direct relationship between vulnerability, quantity of time for patient contemplation, and quality of consent more poignantly questionable than in the intensive care unit (ICU). Rarely are patients (and their substitute decision-makers) more vulnerable than when a person is admitted to an ICU with life-threatening illnesses. Nonetheless and until proven otherwise, ICU patients (or their substitutes) are deemed capable of making life-altering, and sometimes life-ending, and participation in research decisions in one or more moments of time.21 Furthermore, similar to academic regional anesthesiologists, emergency medicine and radiology clinician investigators have limited interaction with their potential study participants, often meeting on a single encounter with no opportunity to recruit and consent their patients in advance of that encounter. Recognizing these limitations, REBs allow for deferred, targeted, or staged consent in order for patients to participate in emergency medicine clinical trials.22 While such urgent or emergent adaptations to the standard informed consent process are not justified for the elective perioperative setting wherein most regional anesthesia clinical trials occur, the same is not true for the radiology research experience. Indeed, low-risk radiology studies are generally approved for enrollment, recruitment, and consent on the same day as the radiological investigation or intervention.23 The radiology (“X-ray”) department may be unlike the operating room environment with respect to heightened patient anxiety; nonetheless, parallels are readily drawn between these 2 settings, including limited time and privacy, the potential for coercion, as well as the low-risk nature of many radiology and regional anesthesia clinical trials. THE POTENTIAL SOLUTIONS One workaround to ensure a robust consent process and patient protection, adopted by many anesthesia research programs, including those at the University of Toronto, has been the anesthesia PAC. Principally purposed to mitigate or optimize patient-related factors that may increase risk of perioperative complications, anesthesia PACs also function as the sole permissible venue (by our local REBs) for subject recruitment by research staff to low-risk clinical anesthesia research trials wherein subjects can provide informed consent days to weeks ahead of surgery. Unfortunately, however, this long-standing workaround is fraught with challenges in appropriate recruitment of participants in that patients attending PACs are likely to be sicker and thus ineligible for study inclusion than those fitter patients who do not attend PAC15 and are more likely eligible for regional anesthesia clinical research. While the idea of coordinating with surgical colleagues to have healthy patients referred to PAC for the secondary purpose of study recruitment may be convenient for investigators, when balanced against creating inconvenience and lost income for patients, the use of hospital resources, health care dollars, and PAC time constraints, the idea quickly loses appeal.16 Another makeshift solution is preadmission telephone calls, which have been used to introduce research protocols and initiate the informed consent process. However, many institutions consider these calls a violation of patient privacy as research personnel callers are not yet within the patient’s circle of care.15 Furthermore, scheduling of calls, anxiety provoked from unsolicited calls originating from the hospital, and constraints in time and manpower represent important ethical and logistical challenges.18,24 Conceivably, the COVID-19 pandemic may alter patient and provider views on telephone or videoconference as means to identify, recruit, enroll, and consent for research protocols. Though the pandemic has already rendered telemedicine more applicable and acceptable to patients and practitioners alike, whether or not it could or should penetrate clinical research programs to a similar degree, especially with respect to preserving the sanctity of privacy within the circle of care, will require ongoing consideration.18,25 Ongoing requirements for universal masking inside of hospitals may further recruitment and consent for clinical trials as clinician investigators must establish a trustful relationship with potential research While it the of a 1 potential of telemedicine is that it does allow and of Thus, the of telemedicine on clinical research programs this pandemic are yet to be and require further including the understanding and of information, perceptions of the consent of ample time for decision-making, patient perceptions of coercion, and to and research recruitment our current understanding of to provide same-day the of evidence of perceived or actual coercion, the perceived of the relationship with the physician the and its low-risk nature would to a of the absolute prohibition on obtaining same-day consent for regional anesthesia clinical research instead of seeking to more workaround which may be more to patients and more patient Most regional anesthesia clinical research trials to and pain in the and In the for regional anesthesia clinical research trials versus that of other anesthesia it is that a proportionate approach to consent protocols is same-day consent practices systematic of patients and who may benefit from participation in regional anesthesia clinical research trials. the of same-day consent and its for clinical research trials would apply to of but this is not anesthesia is unique from other anesthesia in its for healthy and patients undergoing elective surgical procedures in an In clinical trials in other anesthesia as and typically study of or care with generally less patients. recognize that consenting practices for regional anesthesia research trials across North American and consent on the same day as surgery is permissible at some institutions that regional anesthesia research However, our University of the second most in our second only to yet the research hospitals with both the University of and University do not allow same-day consent for recruitment of patients to clinical anesthesia research trials. regarding same-day consent must not be the for other institutions to their regional anesthesia clinical research regional anesthesia investigators to from the COVID-19 pandemic and for growth The COVID-19 pandemic has the and between our clinical regional anesthesia research and our anesthesia an time in which clinical research and knowledge are and health care decisions with and regional anesthesia research has been brought to a While the of consent is not one to be taken the validity of same-day consent for low-risk anesthesia research trials has been Indeed, the NHS has that the of consent can on the risk of study participation and that a universal approach to the of consent is not is the than the time, that is the to the validity of informed consent and subject autonomy.8 same-day consent for low-risk regional anesthesia clinical trials is an burdensome for both clinical investigators and research while we continue to practice it is, in our high time to from such a the the the the

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