World J Surg DOI 10.1007/s00268-014-2588-x
Elements for Adequate Informed Consent in the Surgical Context Hernando Abaunza • Klaus Romero
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Given a history of atrocities and violations of ethical principles, several documents and regulations have been issued by a wide variety of organizations. They aim at ensuring that health care and clinical research adhere to defined ethical principles. A fundamental component was devised to ensure that the individual has been provided the necessary information to make an informed decision regarding health care or participation in clinical research. This article summarizes the history and regulations for informed consent and discusses suggested components for adequate consent forms for daily clinical practice in surgery as well as clinical research.
Introduction After the travesties of World War II and other decades-long atrocities such as the Tuskegee Syphilis Study, efforts were taken to ensure ethical execution of research on human subjects, which then trickled into the everyday clinical practice of medicine [1]. The Declaration of Geneva and the Nu¨remberg Code represent an initial response, followed by the Declaration of Helsinki (DoH) offered by the World Medical Association. The latter was first issued in 1964 and has been updated and amended seven times since then, with the most recent version issued at the General H. Abaunza Asociacio´n Colombiana de Cirugı´a, Calle 100 # 14-63 of. 502, Bogota´, Colombia e-mail: [email protected] K. Romero (&) Critical Path Institute, 1730 East River Road, Tucson, AZ 85718, USA e-mail: [email protected]
Assembly in October 2013 [2]. This version replaces all previous ones and should not be used or cited except for historical purposes. The Common Rule is a rule of ethics regarding biomedical and behavioral research involving human subjects in the United States, governing institutional review boards for oversight of human research. It first came into effect in 1981 following the 1975 revision of the DoH. It is now encapsulated in the 1991 revision of the US Department of Health and Human Services Title 45 CFR 46 (Public Welfare) Subparts A, B, C, and D [3]. It represents the baseline standard of ethics by which any governmentfunded research in the United States is held, and nearly all academic institutions hold their researchers to these statements of rights regardless of funding. The Belmont Report by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was issued on September 30, 1978 and was published in the US Federal Register on April 18, 1979. It summarizes ethical principles and guidelines for research involving human subjects [4]. In general, all of these documents and regulations identify three core principles: (1) respect for persons, which relates to protecting the autonomy of all people and treating them with courtesy and respect and allowing for informed consent; (2) beneficence, which is based on the ‘‘primum non nocere’’ principle while maximizing the benefits for the research project and minimizing risks to the research subjects; and (3) justice, which ensures that reasonable, nonexploitative, and well-considered procedures are administered fairly and equally. These principles remain the basis for the US Health and Human Services (HHS) human subject protection regulations [3, 4]. The Belmont Report also identifies the following three primary areas of application: (1) assessment of risks and benefits to
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ensure that research risks are minimized through careful study designs and that risks are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result; (2) recruitment and selection of subjects, which should be equitable (fair or just; used in the context of selection of participants to indicate that the benefits and burdens of research are fairly distributed) within the confines of the study; (3) informed consent; which pertains to the process for obtaining permission before conducting a health care intervention on a person. Informed consent can be conceptualized as the process of communication between patients and treating physicians that results in authorization or agreement by the patient for a specific medical intervention [5]. To comply with the principles outlined above, patients must be given appropriate and accurate information to make an informed decision to undergo a major treatment or participate in a clinical study. This means that this patient–physician communication process involves much more than getting a patient to sign a written consent form. The signature of such a formal document distinguishes fully informed consent from other forms of patient–physician communications. For an individual to give valid informed consent, three components must be present: disclosure, capacity, voluntariness [6]. Disclosure requires that the subject be supplied with the information necessary to make an autonomous decision, but it must be ensured that subjects have adequate comprehension of the information provided. This requirement implies that the consent form be written in lay language suited to the apprehension skills of a population, and that the level of understanding be assessed during the meeting to discuss the informed consent form. Capacity pertains to the ability of the subject to both understand the information provided and form a reasonable judgment based on the potential consequences of a given decision. Voluntariness refers to the subject’s right to freely exercise decision-making without being subjected to external pressure such as coercion, manipulation, or undue influence. For the purposes of this article, we have separated the description of adequate components of consent forms in the surgical environment into two categories: daily clinical practice and clinical research.
Components of a consent form Daily clinical practice The first operational question that health care providers invariable have pertains to which procedures require informed consent versus a simple form of information exchange between the treating physician and the patient.
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Table 1 Examples of procedures that require informed consent Procedure
Includes (but not limited to)
Surgical procedures
Elective and outpatient
Advanced or complex diagnostic procedures
Endoscopy, biopsies, imaging with contrast media
Oncology-related procedures
Radiation and chemotherapy
Prophylactic procedures
Vaccination
Sensitive diagnostic or screening tests
Human immunodeficiency virus (varies by state)
Table 1 provides examples of such procedures. Informed consent is not needed in an emergency when delayed treatment would be dangerous for the patient [7, 8]. Importantly, some patients may no longer be able to make an informed decision, such as someone with advanced Alzheimer’s disease or an individual in a coma. In these situations, the informed consent process would be required from a surrogate or substitute decision-maker, which is usually a spouse or offspring. Other special situations include the context of emergency lifesaving procedures in patients who cannot make an informed decision and where a surrogate is not immediately available. In this context, informed consent to treatment is not required ‘‘when immediate intervention is necessary to prevent death or serious harm to the patient’’ [7, 8]. It is important to highlight the fact that in these particular cases the physician must judge that treatment is necessary to preserve life or prevent significant harm (e.g., disability or severe suffering). Additionally, the physician must judge that treatment cannot be safely delayed to obtain the patient’s informed consent. However, the presumption that the patient would consent to treatment may be defeated by clear indications to the contrary, such as explicit refusal of treatment by a patient in the absence of any evidence that the patient lacks decision-making capacity. Informed consent for surgical procedures in daily clinical practice poses the challenge of its being applicable to a broader population of subjects (all those individuals who meet the indication for the specific procedure to be performed). It has been shown that after reading, discussing, and signing a consent form, many patients still do not understand basic information about the risks, benefits, and alternatives of their possible treatment options [9]. This clearly defeats the main purpose of the process of informed consent, with multiple causes. Patient-related factors that have been identified include low educational level and limited language proficiency; limited health-specific literacy; learning disabilities; cognitive, hearing, or vision impairments; confusion about the purpose of the consent process [10]. These problems can be compounded by the development of feelings of intimidation, diagnosis-related
World J Surg Table 2 Basic features Initial information
Table 3 US federal requirements for informed consent forms Expanded information
Condition/context: diagnosis (if known)/potential diagnosisa
1. Name and signature of the patient or, if appropriate, legal representative 2. Name of the hospital 3. Name of procedure(s)
Proposed treatment: nature and purpose
Potential harms and benefits
4. Name of all practitioners performing the procedure and individual significant tasks if more than one practitioner
Potential alternatives: nature and purposeb
Potential harms and benefits
5. Risks
Overall: Prognosis
Potential harms and benefits of not undergoing treatment or procedure
6. Benefits 7. Alternative procedures and treatments and their risks 8. Date and time consent has been obtained
a
If the procedure is diagnostic
9. Statement that procedure was explained to the patient or guardian
b
Regardless of costs or extent covered by insurance
10. Signature of person witnessing the consent
stress, or time pressure, which may be increased by the setting and timing of obtaining informed consent. Factors identified as related to the physician or health-care team have included lack of time for up-front patient interaction, inappropriate written or audiovisual materials (excess complexity or insufficient specificity), lack of adequate interpreter support for nonnative speakers, and failure to properly ascertain actual comprehension on the part of the patient [11]. The ethical concept of informed consent is centered on the adequate understanding and agreement on the part of the patient to the potential consequences of their health care. In today’s clinical practice, the concept has been codified in specific laws and regulations [12]. Specific regulations on informed consent are continuously evolving, and today all US states and other countries around the world have legislation that requires varying levels of informed consent [13]. Although the specifics of these regulations vary, they have a common denominator: Failure to obtain informed consent makes practitioners liable for malpractice and/or negligence [14]. However, in varying degrees according to country/state, there are certain exceptions for emergency procedures or when treating patients with legally adjudicated mental incompetence or physical incapacity. The American Medical Association and other groups representing specialists or quality assurance organizations have identified items in which full disclosure is required for an adequate informed consent process, as summarized in Table 2 [5, 6, 12]. Federal regulations define the minimum requirements for a properly executed informed consent form and stipulate that this form must be in the patient’s chart before surgery (Table 3) [15]. These regulations require that the information given to the patient should be communicated in a language or means of communication that the patient is able to understand. The US government also mandates that professional interpretation and translation services be
11. Name and signature of person who explained the procedure to the patient or guardian Source Federal Code [Title 42 C.F.R. § 482.51 (b) (2)] Interpretive Guideline A-0392
available for individuals with limited English proficiency at institutions that receive federal funding. It is important to note that these same regulations also state that informed consent forms must be translated into languages spoken by 5 % or a minimum of 1,000 of a provider’s pool of patients (whichever is less) [16]. However, there is lack of consensus and standardization (both within the United States and globally) in terms of an integrated list of specific procedures that require informed consent versus those that would only require an informal agreement between the patient and the treating physician. Currently, available lists vary based on the interpretation of the applicable regulations on the part of professional groups and institutional boards. As an example, the American College of Obstetrics and Gynecology has developed detailed guidelines for informed consent issues related to sterilization and carrier testing for cystic fibrosis [17]. The Pennsylvania state law mandates that consent be obtained for blood transfusions, chemotherapy, and methadone use as part of a narcotics treatment program [18]. The Joint Commission (formerly known as the Joint Commission on Accreditation of Healthcare Organizations, or JCAHO) recommends that hospitals establish and follow policies that describe which procedures or care, treatment, or services require informed consent [19]. Another area with lack of consensus and standardization is exactly what to disclose in terms of potential risk and available alternatives. In many contexts, regulations rely on the background of what a ‘‘reasonable physician’’ would provide or what a ‘‘reasonable patient’’ would need, leaving a wide range for individual/institutional interpretation [20]. However, most regulations cover the need for the informed consent form to cover all ‘‘material’’ or
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significant risks. In practical terms, it would not be feasible to provide detailed descriptions of every potential risk, so most informed consent processes focus on the most likely and/or serious risks and side effects [20]. Another complicating factor is that the nature and severity of potential complications also depends on the nature and number of underlying conditions or co-morbidities of the patient, making it difficult for a one-size-fits-all form to cover a wide range of contexts [21]. These complicating factors lie on top of the individual levels of understanding that patients have (explained above). All of these factors stress the need to individualize, as much as possible, the informed consent process for each patient. Available evidence to try to address these questions comes from three main types of study: those that come from a specific therapeutic area of interest; those that come from evaluating the process of consent itself over several therapeutic areas; and those that focus on evaluating the response from special patient groups (e.g., vulnerable populations, low literacy) to the informed consent process. There is also paucity of useful metrics and endpoints to monitor the informed consent process from different angles, and many researchers are left with the number of complaints or litigation as the only reliable measurement. This metric, however, might lead to conflicting results that may not be enough to inform meaningful improvements to health care quality or patient safety and satisfaction. The literature shows a wide range of results. A 1990 retrospective survey of 102 colonoscopy patients reported that the majority of individuals (82 %) adequately understood the information they were given and had all their questions properly addressed [22]. These results are in contrast from those of the 1993 study from Lavelle-Jones et al. [23] that focused on 250 interviews from patients undergoing intrathoracic, intraperitoneal, or vascular surgery. That study found that that 69 % of patients reported not reading the consent form before signing it, and approximately 50 % of patients awaiting treatment reported being unhappy with the amount of information they received. That same year, a survey of 81 hospitals in the mid-Atlantic region of the United States reported that only 62 % required informed consent for blood transfusions. The evaluated forms were, however, not standardized and missed key components such as risks and benefits, therapeutic alternatives, and confidentiality [24]. In 1994, Saw et al. [25] interviewed 55 men who had undergone transurethral prostatectomy, among whom 18 % could not recall that retrograde ejaculation was a major risk of the procedure, which had been disclosed with emphasis during the consent process. Also in 1994, a postsurgical survey of 50 individuals found that patients did not adequately understand the purpose of consent forms and frequently perceived them solely as a process of legal protection for
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health care organizations rather than as a source of information and protection for patients. In fact, more than 66 % of patients described the form they were signing as a required legal document, and 50 % actually expressed concerns with some aspect of their procedure [26]. Four years later, Hopper et al. [27] performed an extensive automated evaluation of 616 US consent forms for readability. Results showed that only 29 were at a lower than eighth grade (USA) level, and 461 were higher than a twelfth grade (USA) level. A 1999 study analyzed audio recordings from 1,057 physician–patient encounters and focused on evaluating the completeness of information needed to make informed decisions in each particular context. This analysis found that, in general, only 9 % of decisions made by patients were adequately informed, and 20–38 % of the evaluated encounters met less stringent criteria for completeness set by the investigators [28]. A 2003 study surveyed 117 intensive care unit and 56 internal medicine specialists regarding consenting patients for a range of procedures. Consistently, fewer than 10 % obtained consents from patients for Foley catheterization, whereas more than 90 % did so for various endoscopic procedures. The rates varied from 74 to 94 % for the transfusion of blood products and from 77 to 96 % for diagnostic procedures such as lumbar puncture or paracentesis. The study also reported that the use of ‘‘boiler plate’’ or ‘‘blanket’’ forms was common [21]. The results from studies aimed at improving consent forms have also been mixed. Some research has shown that simplified forms that retain an eighth grade (USA) readability increased the likelihood that patients not only can read the entire form but is able to understand the provided information prior to signing it [29]. Simplification has also been shown to lower patient anxiety levels while improving understanding (measured as the patient’s ability to recall the relevant information) [30]. Additionally, the use of a standardized common informed consent template as a core foundation to develop specific forms for different procedures can also result in increased consent consistency and quality [31]. These conditions are all necessary but not sufficient to ensure that patients not only completely read but adequately understand and properly remember the relevant information about their care and alternative treatments, which emphasizes the need to improve the level of active engagement on the patient’s part in the consent. Reiteration of information through different channels and modes of communication and repeated exposure to information at different times can improve the level of comprehension and the recall ability [32]. These results highlight the fact that current practice of informed consent for daily clinical practice are frequently inadequate. Notwithstanding, it is clear that patients have the right to be provided with clear written and verbal
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information about their care. It leads to adequate understanding on the part of the patient, resulting in a balanced and proper process of shared decision-making. The Temple Health Group has issued recommendations and best practices to improve the informed consent process. They include (1) considering the educational or literacy distribution for the target population to develop adequately formatted and concise documents with appropriate reading levels (mostly lower), rich in relevant graphics; (2) developing a standardized template with consistent language that could then be contextualized for individual procedures; (3) reserving ample time for multiple staff members to deliver a consistent message to patients and providing further explanations on the information initially presented by the treating physician; (4) considering the delivery of information through adjuvant routes such as CDs, DVDs, podcasts; (5) relying on a ‘‘teach-back’’ approach to ensure appropriate information retention; (6) offering patients a range of relevant and reinforcing takehome materials; and (7) making sure that all individuals are aware of their rights and have the opportunity to decline procedures [33]. General recommendations stemming from these considerations for relevant components of an adequate consent form for surgical procedures in daily clinical practice include (1) disclosing the complete nature, purpose, and medical terminology for the proposed procedure; (2) clearly outlining the benefits that the procedure may provide in the context of the patient’s situation/diagnosis/ prognosis/values/quality of life, while also clearly describing the potential harms (risks) that the procedure entails along with potential alternatives and the respective potential benefits and harms (risks); and last but not least, (3) an adequate description of the potential benefits and harms of not undergoing the intended procedure or the alternative treatment options [33]. From the procedural standpoint, it is also thought that adequate consent forms should include not only the patient’s (or legal guardian’s) name and signature, along with the name and signature of the professionals administering and witnessing the consent process, but also the complete name of the organization/institution where the procedure is intended to be performed; the names of all personnel who will execute the procedure with a description of each practitioner’s individual task; the complete date and time at which consent was administered and then obtained; a description of how the procedure was explained to the individual or legal guardian; an outline of any barrier languages encountered during the administration of informed consent and how they were addressed (e.g., sight-translation of the materials, interpretive services on site, by telephone or video).
Clinical research Informed consent for clinical research, which can include observational studies (case control and cohort studies) and clinical trials to evaluate investigational interventions (e.g., pharmaceuticals or surgical procedures), requires more information than the informed consent process for daily clinical practice. In general, informed consent should be obtained for all subjects intended to be enrolled in clinical research. However, it has also been recognized that in certain cases, the requirement for formal informed consent could be waived. In the United States, HHS has identified three provisions in which a waiver or modification to the requirements for obtaining informed consent can occur (for both adults and minors under 18 years of age). Research involving human subjects is typically assigned a risk category of either no greater than minimal risk or greater than minimal risk (some institutions have expanded upon the minimal risk category). The first provision pertains to clinical research in general, in which the respective institutional review board (IRB) or Ethics Committee may waive or alter the requirement of informed consent under 45 CFR 46.116(d), provided that the IRB or Ethics Committee finds and documents that all of the following four conditions are met [15]: (1) the proposed research involves no more than minimal risk to the subjects; (2) the proposed waiver or modification will not adversely affect the rights and welfare of the subjects; (3) the proposed research could not be carried out in practical terms without the waiver or modification; (4) whenever appropriate, the subjects will be provided with additional pertinent information after participation. The second provision pertains to cases in which the proposed research is related to public benefit or service programs. In these cases, the respective IRB or Ethics Committee may approve a consent procedure that modifies some or all of the elements of the informed consent process or waive the requirement to obtain informed consent under HHS regulations at 45 CFR 46.116(c) so long as the respective IRB or Ethics Committee finds and documents that the following conditions are simultaneously met [15]: (1) the proposed research could not be carried out in practical terms without the waiver or modification; and (2) the proposed research is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine public benefit or service programs, procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs. The third provision relates to the context of clinical research in emer-
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gency settings. In this context, the respective IRB or Ethics Committee may also waive the requirement for obtaining informed consent if it finds and documents that the proposed research meets the requirements of the HHS Secretarial waiver under 45 CFR 46.101(i), which allows a waiver of the general requirements for obtaining informed consent in a limited class of research in emergency settings [15]. If this condition is met, the informed consent process is meant to provide the participant with continued communications to inform the decision-making process regarding the start or continued participation in the proposed clinical study. If the proposed clinical research is intended to support the formal regulatory review of a medical product (e.g., drug, biological, medical device, diagnostic test) by the US Food and Drug Administration (FDA), the FDA would allow the respective IRB or Ethics Committee to approve a clinical trial without informed consent from the subjects only (1) if there is an existing emergency exemption from prospective IRB/Ethics Committee approval for an investigational drug, biological, or device; (2) there is an exception from informed consent for planned emergency research; (3) for studies of in vitro diagnostic devices using leftover human specimens that are not individually identifiable; (4) in circumstances when the US President may waive informed consent for military personnel for administering an investigational product to members of the armed forces [15]. From an operational perspective, the informed consent process for clinical research requires multiple meetings and interaction between the potential participant and the researcher. At the first meeting dedicated to the informed consent process, the study’s purpose and objectives should be clearly described, along with the procedures, potential benefits (as an individual, to other patients, to society), potential harms (risks such as adverse events or outcomes), the probability of being assigned to any of the study arms (e.g., control, specific procedures, different doses), the implications of masking (blinding) at different levels, and very importantly the rights the participant has to receive updated information about the study and to accept or decline participation at any point in time [34]. It is also important to clarify to the potential participant that informed consent lasts even after the study ends and even when a decision to withdraw from the study is made. This has important implications for potential future research. Traditionally, conservative consent forms include a provision stipulating that the data collected from the potential participant will be used exclusively for the goals of the study at hand [35]. However, the stagnation of biomedical productivity and the translational gap between preclinical biomedical scientific discoveries and clinical research that can be translated into applicable clinical
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practice advances has led to the advent of consortia approaches and documents such as the FDA’s critical path initiative [36]. This has led to the advent of Public–PrivatePartnerships in the forms of consortia such as those coordinated by the Critical Path Institute [37], which are based on the cornerstone of precompetitive information sharing between stakeholders in the medical product development sector. The leveraging of such information has led to key successes, such as the qualification of novel preclinical biomarkers for nephrotoxicity, the development of the largest standardized database of legacy clinical trial data for Alzheimer’s disease (AD), and the first regulatory endorsement of a quantitative clinical trial simulation tool for mild and moderate AD dementia [38]. However, a limitation that has been identified is the barrier for this kind of information sharing by overly restrictive consent forms that limit the expanded use of data and information from completed clinical trials [35]. Several efforts have been initiated to achieve ethical and scientific consensus on comprehensive options for the informed consent process to include provisions that would allow a potential participant to make a decision on the potential future sharing of their clinical trial data for sound scientific purposes. An interesting case is that of Vanderbilt University’s DNA databank, known as BioVU [39]. In 2007, BioVU began extracting DNA from blood samples of adult patients at Vanderbilt that otherwise would be discarded. To date, it has acquired nearly 75,000 DNA samples that are linked to their matching electronic medical records. Both the samples and the records are deidentified in the sense that all personal information has been scrubbed to guarantee each subject’s anonymity. In 2010, BioVU also began receiving samples from pediatric patients [40]. The informed consent process for Vanderbilt patients undergoing treatment includes a provision that allows them to ‘‘opt out’’ of the databank. This databank has proven a valuable resource for pharmacogenomics and personalized medical research [41]. In this context, it is important to highlight the fact that if the proposed research’s intent is to utilize or share protected health information (PHI), the research must be conducted in accordance with the Privacy Rule of the Health Insurance Portability and Accountability Act (HIPAA), which provides federal protections for individually identifiable health information held by covered entities and their business associates. It gives patients an array of rights with respect to that information [15]. This means that whenever a researcher applies for a waiver of documentation of informed consent, an additional waiver or modification of HIPAA authorization must also be procured. In these cases, the respective IRB or Ethics Committee can grant the waiver of modification if it is deemed that the following criteria are met: (1) the proposed research could
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not practicably be conducted without the waiver or modification; (2) the proposed research could not practicably be conducted without access to and use of the PHI; (3) the proposed research includes an appropriate plan to protect health information identifiers from improper use or disclosure along with an adequate plan to destroy identifiers at the earliest opportunity absent a health or research justification or legal requirement to retain them, and appropriate written assurances that the PHI will not be used or disclosed to a third party except as required by law, for authorized oversight of the proposed research or for other research uses and disclosures permitted by the Privacy Rule [15]. Although the consent form process for clinical research has a higher level of standardization, some interinstitutional variability remains. In general, however, the process starts with a preliminary meeting at which an individual researcher or a team provides the patient with the informed consent document followed by a run-through and explanation of the document [34]. It is also important to let potential participants know that they are allowed to be joined by another party (family or friend), who can provide support and help the individual keep track of the information being offered. As with the informed consent process for daily clinical practice, the information provided to the potential participant should be put in the context of the individual’s cultural and educational background. Also, the dialogue should be carried out at a pace comfortable for the potential participant, allowing adequate time for the individual to process the information and ask questions. In this context, it is also recommended that other media be employed—e.g., video, audio, interactive media webcasts and podcasts—always keeping the individual’s background in mind [34]. Time is also a factor for a potential participant to process all the information regarding the clinical study, potential procedures, alternatives, and potential benefits and harms. For this reason, the subject should be given a copy of the consent form to take home, so that he or she and potential trusted advisors such as family, friends, counselors, therapists, or patient representatives can discuss the information. Only then can the patient make an informed decision. Every effort should be made by the researchers to be sure that the individual understands the information provided. This can be done by having the subject fill out a written questionnaire, respond to verbal questions, or use a teach-back method in which the individual expresses in his or her own words what the study objectives are, what participation entails, the procedures and treatments being offered, the randomization and blinding process (if applicable according to the study design), the potential benefits and harms, the use of data generated by the trial, and the right to decline participation at any time. As the clinical
Table 4 Suggested information to be included in adequate consent forms for clinical research 1. Research objectives for the clinical triala 2. What is expected from the participant—what will be done and how long he or she is expected to take part 3. Potential benefits (to the individual patient, to the patient population, and to the advancement of science) 4. What is known and not known about the drug or procedure being evaluated 5. Any potential risks to the subject (if known) 6. Whom the subject should contact with questions about or problems with the study 7. Other possible treatment options 8. A clear explanation that the subject has the right to stop participating in the study with no penalty and opt for standard medical care at any time 9. How the subject’s personal information will be protected a
A contact person and phone number for more information should always be provided to the subject at the first meeting
trial goes on, the research team may make new discoveries that could affect your health, well-being, or willingness to remain in the study. Once the study is underway, adaptive designs or protocol amendments to standard designs may warrant changes to the informed consent form, which requires updating the consent form process, in which case all of the same provisions apply, as discussed previously [34]. Table 4 describes the suggested information that adequate consent forms for clinical research should have. As explained before, the main objective is to allow the potential participant to make an informed decision and to be sure that the subject is able to choose freely whether to enroll in (or stay in) the study. When it is a minor undergoing the informed consent process, both parents (or legal guardians) may be required to sign the form for the subject to take part in the clinical trial [42]. The subject should always be provided with a copy of the consent form. The potential participant should also be offered a copy of the study protocol that describes all the details of the clinical trial. According to US regulations, no informed consent document may contain statements that explicitly or tacitly state that the subject would give up (waive) any legal rights. It also may not include any provision releasing (directly or indirectly) the investigator, physician, sponsor, or facility from liability if they are negligent or careless [43]. As can be seen, the informed consent process is an ongoing continuum during which information is presented to individuals to enable them to decide voluntarily whether to participate or continue participation in a research study. As in the case of daily clinical practice, reading and signing the consent form document does not replace active interaction between the investigator and individual deciding to
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World J Surg Table 5 Considerations to keep in mind when initiating the consent process 1. The potential subject’s physical, sociocultural, and mental state should be recognized 2. The consenting process should occur as a time continuum that may include days or weeks to allow time for the individual to consider whether to participate in the study and to discuss the research with his or her trusted advisors 3. It is recommended that the research information and consent document be presented and clarified separately from standard clinical or hospital information. Also, the difference between the conduct of the research and daily clinical practice should be emphasized 4. The participant should always be provided with a copy of the consent form 5. Investigators/members of the team should be available to address any questions or concerns the participant may have during the decision-making process (and certainly during the execution of the trial) 6. A family member or person involved in the care of the participant should be encouraged to participate in the consent process 7. Beyond the standard delivery of complete information about the clinical trial, provision of active methods to evaluate the subject’s level of understanding of the information should be considered 8. Investigators conducting the consent process should ask the subject if he or she has been given adequate time to make a decision and if the consent document and complementary information has been provided in a language they can understand 9. Any and all possibilities for coercion or undue influence should be actively avoided and minimized while providing information about the research and during the consent process
participate. Table 5 presents some important considerations to keep in mind when initiating the consent process. The language and documentation in the consent form— with special emphasis on the research objectives, trial duration, experimental procedures, therapeutic alternatives, and potential harms and benefits—must be written in a culturally appropriate manner and at an intellectual level usually recommended to be at the US school system’s fifth grade reading ability. The written document used for the consent process forms the basis for formal documentation and for the participants’ future reference. As new information about the study becomes available, the consent form should be updated in a timely fashion. The respective IRB or Ethics Committee must then approve of all changes. In the United States, the process of obtaining signed informed consent must comply with the requirements of 45 Code of Federal Regulations 46.116, and the consent form must contain the ‘‘Required Elements of Informed Consent’’ [15]. It is also mandated that informed consent should be obtained in person (no telephone or remote means are allowed) from the participant.
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Table 6 Recommended components for enrollment notes 1. If a pregnancy test is required, results should be reported in the note, describing the sample used (blood or urine), date, and specific results 2. A brief description of the study design should be outlined, including randomization into potential arms, masking level and methods, drugs, devices or procedures evaluated in the study, and the route and length of treatment. If possible, provide the time of first treatment and the tolerance level for such treatment 3. Record who dispensed the study drug (when applicable) and who administered the procedures related to the study (when applicable) 4. If the design calls for the patient to self-administer any study medication or procedure, the treatment provided to the participant for this purpose should be documenteda 5. The fact that no protocol procedures were done prior to consent should be documented. If a test/procedure was done for standard care, it should be so noted 6. A note documenting that the study has been discussed with the patient and that all questions were answered. should be included 7. The contact information for whom to call with questions/ problems related to the study should be included a
Drug administration, dosing and recording, return demonstration of successful administration to patient/family, return of study medication, and if the patient/family has a contact number to call for questions or problems)
For the informed consent form to be considered valid, the following information should be filled out in its entirety: (1) printed full name and signature of person(s) administering the informed consent process, properly dated; (2) printed full name and signature of the research participant (or legal representative), properly dated. However, a signed and dated consent form is not sufficient for adequately documenting the informed consent process. A progress report should be developed and filled out at each encounter that documents the communication between investigator and subject about the research. Such reports should include what was discussed, how every question from the subject was addressed, if the subject received a copy of the consent form to take home, or if the subject signed the consent form. The integration of these reports as a function of time documents the consenting process [34, 35, 42, 43]. At the time of the first encounter for the informed consent process, a written study enrollment note should be included in the patient’s medical record or shadow file. For both inpatient and outpatient studies involving greater than minimal risk, the original signed consent form must be included in the medical record [34, 43]. Table 6 describes recommended components for properly dated and timed enrollment notes. For inpatient or outpatient studies that have aboveminimal risk, the investigator should include the Informed Consent Document in the medical chart [43]. For minimal-
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risk outpatient studies, it is recommended that the investigator put a copy of the informed consent document in the subject’s medical record. Importantly, if the informed consent document is placed in the medical record, it should be indicated in the informed consent document. In addition, the research subject should also be informed if a separate or new medical record will be created because of participation in a research study [34, 42]. In certain instances that have special considerations for confidentiality reasons or clinical research involving sensitive topics, an investigator may wish to refrain from placing a copy of the consent form in the medical record [44]. In such instances, at a minimum the date and time of informed consent should be included along with a note stating that the individual has been enrolled in a research study evaluating a drug or procedure. If the research protocol coup affect the research subject’s health, the statement in the chart must include an adequate description of the intervention required by other health care professionals to deal with any potential medical conditions. Special considerations According to US regulations, ‘‘children’’ are defined as ‘‘persons who have not attained the legal age for consent to treatments or procedures involved in the research under the applicable law of the jurisdiction in which the research will be conducted’’ [45 C.F.R. 46.202(a)] [15]. In most of the United States, the age of adulthood is 18 years unless a person has reached a lower age (depending on the jurisdiction) and has been emancipated by court order, marriage, or active military duty. Thus, in practical terms, persons under 18 years of age are considered ‘‘children’’ for research purposes, and their entry into research requires consent of the parents or legal guardians. Children may not be enrolled in research without ‘‘permission’’ (agreement under standard consent provisions) of a parent or guardian (and of both parents for research of greater than minimal risk, with no prospect of direct benefit to individual subjects, see Section 6.2.1). According to US regulations, a ‘‘guardian’’ is a person ‘‘who is authorized under applicable state or local law to consent on behalf of a child to general medical care’’ [45 C.F.R. 46. 402(e)] [15]. To enroll the child, guardianship papers should be presented. There may be other legal mechanisms of granting permission to a person other than the parent to consent to health care that may suffice as well (e.g., health care power of attorney). The term informed assent describes the process whereby minors may agree to participate in clinical trials. In addition to parental/guardian permission, investigators are required to obtain the ‘‘assent’’ of the child. Assent is ‘‘a
child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent’’ [45 C.F.R. Section 46.402(b)] [15]. Some organizations recommend that assent be obtained from all children age 7 and older] unless the nature of the research dictates otherwise (e.g., research on brain-injured children) [42]. As can be seen, the informed consent document is only one part of the larger process of informed consent that occurs between the potential research participant and members of the research team. The informed consent document should be understandable to the research participants involved.
Discussion Investigators are usually concerned with how to ensure that the consent process provides the appropriate amount of information in a way that the potential participant can adequately understand. Three basic approaches have been described [12]. The ‘‘reasonable physician standard’’ is based on considerations regarding what information a typical physician would provide about a particular treatment or procedure. As this is centered on the physician’s perspective, it is probably not enough because in most cultural and health care contexts the information disclosed by physicians tends to be limited. A second approach, known as the ‘‘reasonable patient/participant standard,’’ is centered on what a usual subject would need to know to make an informed decision regarding a treatment or participation in a clinical study. The ‘‘subjective standard’’ is centered on what a particular individual would need to know and understand to make an informed decision regarding treatment or participation in a clinical study [12]. This standard is challenging to incorporate fully into practice, given that it requires tailoring information for each individual. However, it is also important to consider that placing a focus on the cultural context of the various populations of subjects who could have the indication for a specific treatment or procedure or who could be offered participation in a given clinical trial can help bring an informed consent process based on the ‘‘reasonable patient/ participant standard’’ closer to one based on the ‘‘subjective standard’’ [12]. In addition, the modern day of information sharing and ‘‘big data’’ that could help advance biomedical research in a much more efficient manner calls for consideration of such provisions into the informed consent process [37]. Initial efforts in this area are well underway, and Vanderbilt’s BiuVU ‘‘opt-out’’ process could be a model for further evolution of the informed consent process [39].
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Conclusions The informed consent process consists of a continuous dialogue between research participant and investigator. All measures should be taken to ensure that the concerns and questions from the research subject are properly addressed and there is an adequate level of understanding regarding the research objective and conduct of the study as well as the potential harms and benefits. It is the only way to ensure that the rights of research participants are protected and that the integrity and utility of the informed consent process is maintained.
15.
16.
17.
18. 19.
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40. McGregor TL, Van Driest SL, Brothers KB et al (2013) Inclusion of pediatric samples in an opt-out biorepository linking DNA to de-identified medical records: pediatric BioVU. Clin Pharmacol Ther 93:204–211 41. Oetjens MT, Denny JC, Ritchie MD et al (2013) Assessment of a pharmacogenomic marker panel in a polypharmacy population identified from electronic medical records. Pharmacogenomics 14:735–744 42. Murat I, Sabourdin N, Balestrat E et al (2013) Informed consent for standard procedures and for clinical research in paediatric anaesthesia. Ann Fr Anesth Reanim 32:e61–e63 43. Davidson AJ, O’Brien M (2009) Ethics and medical research in children. Paediatr Anaesth 19:994–1004 44. Lo B, Grady C, Working Group on Ethics of the International AIDS Society (2013) Ethical considerations in HIV cure research: points to consider. Curr Opin HIV AIDS 8:243–249
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Elements for Adequate Informed Consent in the Surgical Context Hernando Abaunza • Klaus Romero
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Given a history of atrocities and violations of ethical principles, several documents and regulations have been issued by a wide variety of organizations. They aim at ensuring that health care and clinical research adhere to defined ethical principles. A fundamental component was devised to ensure that the individual has been provided the necessary information to make an informed decision regarding health care or participation in clinical research. This article summarizes the history and regulations for informed consent and discusses suggested components for adequate consent forms for daily clinical practice in surgery as well as clinical research.
Introduction After the travesties of World War II and other decades-long atrocities such as the Tuskegee Syphilis Study, efforts were taken to ensure ethical execution of research on human subjects, which then trickled into the everyday clinical practice of medicine [1]. The Declaration of Geneva and the Nu¨remberg Code represent an initial response, followed by the Declaration of Helsinki (DoH) offered by the World Medical Association. The latter was first issued in 1964 and has been updated and amended seven times since then, with the most recent version issued at the General H. Abaunza Asociacio´n Colombiana de Cirugı´a, Calle 100 # 14-63 of. 502, Bogota´, Colombia e-mail: [email protected] K. Romero (&) Critical Path Institute, 1730 East River Road, Tucson, AZ 85718, USA e-mail: [email protected]
Assembly in October 2013 [2]. This version replaces all previous ones and should not be used or cited except for historical purposes. The Common Rule is a rule of ethics regarding biomedical and behavioral research involving human subjects in the United States, governing institutional review boards for oversight of human research. It first came into effect in 1981 following the 1975 revision of the DoH. It is now encapsulated in the 1991 revision of the US Department of Health and Human Services Title 45 CFR 46 (Public Welfare) Subparts A, B, C, and D [3]. It represents the baseline standard of ethics by which any governmentfunded research in the United States is held, and nearly all academic institutions hold their researchers to these statements of rights regardless of funding. The Belmont Report by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was issued on September 30, 1978 and was published in the US Federal Register on April 18, 1979. It summarizes ethical principles and guidelines for research involving human subjects [4]. In general, all of these documents and regulations identify three core principles: (1) respect for persons, which relates to protecting the autonomy of all people and treating them with courtesy and respect and allowing for informed consent; (2) beneficence, which is based on the ‘‘primum non nocere’’ principle while maximizing the benefits for the research project and minimizing risks to the research subjects; and (3) justice, which ensures that reasonable, nonexploitative, and well-considered procedures are administered fairly and equally. These principles remain the basis for the US Health and Human Services (HHS) human subject protection regulations [3, 4]. The Belmont Report also identifies the following three primary areas of application: (1) assessment of risks and benefits to
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ensure that research risks are minimized through careful study designs and that risks are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result; (2) recruitment and selection of subjects, which should be equitable (fair or just; used in the context of selection of participants to indicate that the benefits and burdens of research are fairly distributed) within the confines of the study; (3) informed consent; which pertains to the process for obtaining permission before conducting a health care intervention on a person. Informed consent can be conceptualized as the process of communication between patients and treating physicians that results in authorization or agreement by the patient for a specific medical intervention [5]. To comply with the principles outlined above, patients must be given appropriate and accurate information to make an informed decision to undergo a major treatment or participate in a clinical study. This means that this patient–physician communication process involves much more than getting a patient to sign a written consent form. The signature of such a formal document distinguishes fully informed consent from other forms of patient–physician communications. For an individual to give valid informed consent, three components must be present: disclosure, capacity, voluntariness [6]. Disclosure requires that the subject be supplied with the information necessary to make an autonomous decision, but it must be ensured that subjects have adequate comprehension of the information provided. This requirement implies that the consent form be written in lay language suited to the apprehension skills of a population, and that the level of understanding be assessed during the meeting to discuss the informed consent form. Capacity pertains to the ability of the subject to both understand the information provided and form a reasonable judgment based on the potential consequences of a given decision. Voluntariness refers to the subject’s right to freely exercise decision-making without being subjected to external pressure such as coercion, manipulation, or undue influence. For the purposes of this article, we have separated the description of adequate components of consent forms in the surgical environment into two categories: daily clinical practice and clinical research.
Components of a consent form Daily clinical practice The first operational question that health care providers invariable have pertains to which procedures require informed consent versus a simple form of information exchange between the treating physician and the patient.
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Table 1 Examples of procedures that require informed consent Procedure
Includes (but not limited to)
Surgical procedures
Elective and outpatient
Advanced or complex diagnostic procedures
Endoscopy, biopsies, imaging with contrast media
Oncology-related procedures
Radiation and chemotherapy
Prophylactic procedures
Vaccination
Sensitive diagnostic or screening tests
Human immunodeficiency virus (varies by state)
Table 1 provides examples of such procedures. Informed consent is not needed in an emergency when delayed treatment would be dangerous for the patient [7, 8]. Importantly, some patients may no longer be able to make an informed decision, such as someone with advanced Alzheimer’s disease or an individual in a coma. In these situations, the informed consent process would be required from a surrogate or substitute decision-maker, which is usually a spouse or offspring. Other special situations include the context of emergency lifesaving procedures in patients who cannot make an informed decision and where a surrogate is not immediately available. In this context, informed consent to treatment is not required ‘‘when immediate intervention is necessary to prevent death or serious harm to the patient’’ [7, 8]. It is important to highlight the fact that in these particular cases the physician must judge that treatment is necessary to preserve life or prevent significant harm (e.g., disability or severe suffering). Additionally, the physician must judge that treatment cannot be safely delayed to obtain the patient’s informed consent. However, the presumption that the patient would consent to treatment may be defeated by clear indications to the contrary, such as explicit refusal of treatment by a patient in the absence of any evidence that the patient lacks decision-making capacity. Informed consent for surgical procedures in daily clinical practice poses the challenge of its being applicable to a broader population of subjects (all those individuals who meet the indication for the specific procedure to be performed). It has been shown that after reading, discussing, and signing a consent form, many patients still do not understand basic information about the risks, benefits, and alternatives of their possible treatment options [9]. This clearly defeats the main purpose of the process of informed consent, with multiple causes. Patient-related factors that have been identified include low educational level and limited language proficiency; limited health-specific literacy; learning disabilities; cognitive, hearing, or vision impairments; confusion about the purpose of the consent process [10]. These problems can be compounded by the development of feelings of intimidation, diagnosis-related
World J Surg Table 2 Basic features Initial information
Table 3 US federal requirements for informed consent forms Expanded information
Condition/context: diagnosis (if known)/potential diagnosisa
1. Name and signature of the patient or, if appropriate, legal representative 2. Name of the hospital 3. Name of procedure(s)
Proposed treatment: nature and purpose
Potential harms and benefits
4. Name of all practitioners performing the procedure and individual significant tasks if more than one practitioner
Potential alternatives: nature and purposeb
Potential harms and benefits
5. Risks
Overall: Prognosis
Potential harms and benefits of not undergoing treatment or procedure
6. Benefits 7. Alternative procedures and treatments and their risks 8. Date and time consent has been obtained
a
If the procedure is diagnostic
9. Statement that procedure was explained to the patient or guardian
b
Regardless of costs or extent covered by insurance
10. Signature of person witnessing the consent
stress, or time pressure, which may be increased by the setting and timing of obtaining informed consent. Factors identified as related to the physician or health-care team have included lack of time for up-front patient interaction, inappropriate written or audiovisual materials (excess complexity or insufficient specificity), lack of adequate interpreter support for nonnative speakers, and failure to properly ascertain actual comprehension on the part of the patient [11]. The ethical concept of informed consent is centered on the adequate understanding and agreement on the part of the patient to the potential consequences of their health care. In today’s clinical practice, the concept has been codified in specific laws and regulations [12]. Specific regulations on informed consent are continuously evolving, and today all US states and other countries around the world have legislation that requires varying levels of informed consent [13]. Although the specifics of these regulations vary, they have a common denominator: Failure to obtain informed consent makes practitioners liable for malpractice and/or negligence [14]. However, in varying degrees according to country/state, there are certain exceptions for emergency procedures or when treating patients with legally adjudicated mental incompetence or physical incapacity. The American Medical Association and other groups representing specialists or quality assurance organizations have identified items in which full disclosure is required for an adequate informed consent process, as summarized in Table 2 [5, 6, 12]. Federal regulations define the minimum requirements for a properly executed informed consent form and stipulate that this form must be in the patient’s chart before surgery (Table 3) [15]. These regulations require that the information given to the patient should be communicated in a language or means of communication that the patient is able to understand. The US government also mandates that professional interpretation and translation services be
11. Name and signature of person who explained the procedure to the patient or guardian Source Federal Code [Title 42 C.F.R. § 482.51 (b) (2)] Interpretive Guideline A-0392
available for individuals with limited English proficiency at institutions that receive federal funding. It is important to note that these same regulations also state that informed consent forms must be translated into languages spoken by 5 % or a minimum of 1,000 of a provider’s pool of patients (whichever is less) [16]. However, there is lack of consensus and standardization (both within the United States and globally) in terms of an integrated list of specific procedures that require informed consent versus those that would only require an informal agreement between the patient and the treating physician. Currently, available lists vary based on the interpretation of the applicable regulations on the part of professional groups and institutional boards. As an example, the American College of Obstetrics and Gynecology has developed detailed guidelines for informed consent issues related to sterilization and carrier testing for cystic fibrosis [17]. The Pennsylvania state law mandates that consent be obtained for blood transfusions, chemotherapy, and methadone use as part of a narcotics treatment program [18]. The Joint Commission (formerly known as the Joint Commission on Accreditation of Healthcare Organizations, or JCAHO) recommends that hospitals establish and follow policies that describe which procedures or care, treatment, or services require informed consent [19]. Another area with lack of consensus and standardization is exactly what to disclose in terms of potential risk and available alternatives. In many contexts, regulations rely on the background of what a ‘‘reasonable physician’’ would provide or what a ‘‘reasonable patient’’ would need, leaving a wide range for individual/institutional interpretation [20]. However, most regulations cover the need for the informed consent form to cover all ‘‘material’’ or
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significant risks. In practical terms, it would not be feasible to provide detailed descriptions of every potential risk, so most informed consent processes focus on the most likely and/or serious risks and side effects [20]. Another complicating factor is that the nature and severity of potential complications also depends on the nature and number of underlying conditions or co-morbidities of the patient, making it difficult for a one-size-fits-all form to cover a wide range of contexts [21]. These complicating factors lie on top of the individual levels of understanding that patients have (explained above). All of these factors stress the need to individualize, as much as possible, the informed consent process for each patient. Available evidence to try to address these questions comes from three main types of study: those that come from a specific therapeutic area of interest; those that come from evaluating the process of consent itself over several therapeutic areas; and those that focus on evaluating the response from special patient groups (e.g., vulnerable populations, low literacy) to the informed consent process. There is also paucity of useful metrics and endpoints to monitor the informed consent process from different angles, and many researchers are left with the number of complaints or litigation as the only reliable measurement. This metric, however, might lead to conflicting results that may not be enough to inform meaningful improvements to health care quality or patient safety and satisfaction. The literature shows a wide range of results. A 1990 retrospective survey of 102 colonoscopy patients reported that the majority of individuals (82 %) adequately understood the information they were given and had all their questions properly addressed [22]. These results are in contrast from those of the 1993 study from Lavelle-Jones et al. [23] that focused on 250 interviews from patients undergoing intrathoracic, intraperitoneal, or vascular surgery. That study found that that 69 % of patients reported not reading the consent form before signing it, and approximately 50 % of patients awaiting treatment reported being unhappy with the amount of information they received. That same year, a survey of 81 hospitals in the mid-Atlantic region of the United States reported that only 62 % required informed consent for blood transfusions. The evaluated forms were, however, not standardized and missed key components such as risks and benefits, therapeutic alternatives, and confidentiality [24]. In 1994, Saw et al. [25] interviewed 55 men who had undergone transurethral prostatectomy, among whom 18 % could not recall that retrograde ejaculation was a major risk of the procedure, which had been disclosed with emphasis during the consent process. Also in 1994, a postsurgical survey of 50 individuals found that patients did not adequately understand the purpose of consent forms and frequently perceived them solely as a process of legal protection for
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health care organizations rather than as a source of information and protection for patients. In fact, more than 66 % of patients described the form they were signing as a required legal document, and 50 % actually expressed concerns with some aspect of their procedure [26]. Four years later, Hopper et al. [27] performed an extensive automated evaluation of 616 US consent forms for readability. Results showed that only 29 were at a lower than eighth grade (USA) level, and 461 were higher than a twelfth grade (USA) level. A 1999 study analyzed audio recordings from 1,057 physician–patient encounters and focused on evaluating the completeness of information needed to make informed decisions in each particular context. This analysis found that, in general, only 9 % of decisions made by patients were adequately informed, and 20–38 % of the evaluated encounters met less stringent criteria for completeness set by the investigators [28]. A 2003 study surveyed 117 intensive care unit and 56 internal medicine specialists regarding consenting patients for a range of procedures. Consistently, fewer than 10 % obtained consents from patients for Foley catheterization, whereas more than 90 % did so for various endoscopic procedures. The rates varied from 74 to 94 % for the transfusion of blood products and from 77 to 96 % for diagnostic procedures such as lumbar puncture or paracentesis. The study also reported that the use of ‘‘boiler plate’’ or ‘‘blanket’’ forms was common [21]. The results from studies aimed at improving consent forms have also been mixed. Some research has shown that simplified forms that retain an eighth grade (USA) readability increased the likelihood that patients not only can read the entire form but is able to understand the provided information prior to signing it [29]. Simplification has also been shown to lower patient anxiety levels while improving understanding (measured as the patient’s ability to recall the relevant information) [30]. Additionally, the use of a standardized common informed consent template as a core foundation to develop specific forms for different procedures can also result in increased consent consistency and quality [31]. These conditions are all necessary but not sufficient to ensure that patients not only completely read but adequately understand and properly remember the relevant information about their care and alternative treatments, which emphasizes the need to improve the level of active engagement on the patient’s part in the consent. Reiteration of information through different channels and modes of communication and repeated exposure to information at different times can improve the level of comprehension and the recall ability [32]. These results highlight the fact that current practice of informed consent for daily clinical practice are frequently inadequate. Notwithstanding, it is clear that patients have the right to be provided with clear written and verbal
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information about their care. It leads to adequate understanding on the part of the patient, resulting in a balanced and proper process of shared decision-making. The Temple Health Group has issued recommendations and best practices to improve the informed consent process. They include (1) considering the educational or literacy distribution for the target population to develop adequately formatted and concise documents with appropriate reading levels (mostly lower), rich in relevant graphics; (2) developing a standardized template with consistent language that could then be contextualized for individual procedures; (3) reserving ample time for multiple staff members to deliver a consistent message to patients and providing further explanations on the information initially presented by the treating physician; (4) considering the delivery of information through adjuvant routes such as CDs, DVDs, podcasts; (5) relying on a ‘‘teach-back’’ approach to ensure appropriate information retention; (6) offering patients a range of relevant and reinforcing takehome materials; and (7) making sure that all individuals are aware of their rights and have the opportunity to decline procedures [33]. General recommendations stemming from these considerations for relevant components of an adequate consent form for surgical procedures in daily clinical practice include (1) disclosing the complete nature, purpose, and medical terminology for the proposed procedure; (2) clearly outlining the benefits that the procedure may provide in the context of the patient’s situation/diagnosis/ prognosis/values/quality of life, while also clearly describing the potential harms (risks) that the procedure entails along with potential alternatives and the respective potential benefits and harms (risks); and last but not least, (3) an adequate description of the potential benefits and harms of not undergoing the intended procedure or the alternative treatment options [33]. From the procedural standpoint, it is also thought that adequate consent forms should include not only the patient’s (or legal guardian’s) name and signature, along with the name and signature of the professionals administering and witnessing the consent process, but also the complete name of the organization/institution where the procedure is intended to be performed; the names of all personnel who will execute the procedure with a description of each practitioner’s individual task; the complete date and time at which consent was administered and then obtained; a description of how the procedure was explained to the individual or legal guardian; an outline of any barrier languages encountered during the administration of informed consent and how they were addressed (e.g., sight-translation of the materials, interpretive services on site, by telephone or video).
Clinical research Informed consent for clinical research, which can include observational studies (case control and cohort studies) and clinical trials to evaluate investigational interventions (e.g., pharmaceuticals or surgical procedures), requires more information than the informed consent process for daily clinical practice. In general, informed consent should be obtained for all subjects intended to be enrolled in clinical research. However, it has also been recognized that in certain cases, the requirement for formal informed consent could be waived. In the United States, HHS has identified three provisions in which a waiver or modification to the requirements for obtaining informed consent can occur (for both adults and minors under 18 years of age). Research involving human subjects is typically assigned a risk category of either no greater than minimal risk or greater than minimal risk (some institutions have expanded upon the minimal risk category). The first provision pertains to clinical research in general, in which the respective institutional review board (IRB) or Ethics Committee may waive or alter the requirement of informed consent under 45 CFR 46.116(d), provided that the IRB or Ethics Committee finds and documents that all of the following four conditions are met [15]: (1) the proposed research involves no more than minimal risk to the subjects; (2) the proposed waiver or modification will not adversely affect the rights and welfare of the subjects; (3) the proposed research could not be carried out in practical terms without the waiver or modification; (4) whenever appropriate, the subjects will be provided with additional pertinent information after participation. The second provision pertains to cases in which the proposed research is related to public benefit or service programs. In these cases, the respective IRB or Ethics Committee may approve a consent procedure that modifies some or all of the elements of the informed consent process or waive the requirement to obtain informed consent under HHS regulations at 45 CFR 46.116(c) so long as the respective IRB or Ethics Committee finds and documents that the following conditions are simultaneously met [15]: (1) the proposed research could not be carried out in practical terms without the waiver or modification; and (2) the proposed research is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine public benefit or service programs, procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs. The third provision relates to the context of clinical research in emer-
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gency settings. In this context, the respective IRB or Ethics Committee may also waive the requirement for obtaining informed consent if it finds and documents that the proposed research meets the requirements of the HHS Secretarial waiver under 45 CFR 46.101(i), which allows a waiver of the general requirements for obtaining informed consent in a limited class of research in emergency settings [15]. If this condition is met, the informed consent process is meant to provide the participant with continued communications to inform the decision-making process regarding the start or continued participation in the proposed clinical study. If the proposed clinical research is intended to support the formal regulatory review of a medical product (e.g., drug, biological, medical device, diagnostic test) by the US Food and Drug Administration (FDA), the FDA would allow the respective IRB or Ethics Committee to approve a clinical trial without informed consent from the subjects only (1) if there is an existing emergency exemption from prospective IRB/Ethics Committee approval for an investigational drug, biological, or device; (2) there is an exception from informed consent for planned emergency research; (3) for studies of in vitro diagnostic devices using leftover human specimens that are not individually identifiable; (4) in circumstances when the US President may waive informed consent for military personnel for administering an investigational product to members of the armed forces [15]. From an operational perspective, the informed consent process for clinical research requires multiple meetings and interaction between the potential participant and the researcher. At the first meeting dedicated to the informed consent process, the study’s purpose and objectives should be clearly described, along with the procedures, potential benefits (as an individual, to other patients, to society), potential harms (risks such as adverse events or outcomes), the probability of being assigned to any of the study arms (e.g., control, specific procedures, different doses), the implications of masking (blinding) at different levels, and very importantly the rights the participant has to receive updated information about the study and to accept or decline participation at any point in time [34]. It is also important to clarify to the potential participant that informed consent lasts even after the study ends and even when a decision to withdraw from the study is made. This has important implications for potential future research. Traditionally, conservative consent forms include a provision stipulating that the data collected from the potential participant will be used exclusively for the goals of the study at hand [35]. However, the stagnation of biomedical productivity and the translational gap between preclinical biomedical scientific discoveries and clinical research that can be translated into applicable clinical
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practice advances has led to the advent of consortia approaches and documents such as the FDA’s critical path initiative [36]. This has led to the advent of Public–PrivatePartnerships in the forms of consortia such as those coordinated by the Critical Path Institute [37], which are based on the cornerstone of precompetitive information sharing between stakeholders in the medical product development sector. The leveraging of such information has led to key successes, such as the qualification of novel preclinical biomarkers for nephrotoxicity, the development of the largest standardized database of legacy clinical trial data for Alzheimer’s disease (AD), and the first regulatory endorsement of a quantitative clinical trial simulation tool for mild and moderate AD dementia [38]. However, a limitation that has been identified is the barrier for this kind of information sharing by overly restrictive consent forms that limit the expanded use of data and information from completed clinical trials [35]. Several efforts have been initiated to achieve ethical and scientific consensus on comprehensive options for the informed consent process to include provisions that would allow a potential participant to make a decision on the potential future sharing of their clinical trial data for sound scientific purposes. An interesting case is that of Vanderbilt University’s DNA databank, known as BioVU [39]. In 2007, BioVU began extracting DNA from blood samples of adult patients at Vanderbilt that otherwise would be discarded. To date, it has acquired nearly 75,000 DNA samples that are linked to their matching electronic medical records. Both the samples and the records are deidentified in the sense that all personal information has been scrubbed to guarantee each subject’s anonymity. In 2010, BioVU also began receiving samples from pediatric patients [40]. The informed consent process for Vanderbilt patients undergoing treatment includes a provision that allows them to ‘‘opt out’’ of the databank. This databank has proven a valuable resource for pharmacogenomics and personalized medical research [41]. In this context, it is important to highlight the fact that if the proposed research’s intent is to utilize or share protected health information (PHI), the research must be conducted in accordance with the Privacy Rule of the Health Insurance Portability and Accountability Act (HIPAA), which provides federal protections for individually identifiable health information held by covered entities and their business associates. It gives patients an array of rights with respect to that information [15]. This means that whenever a researcher applies for a waiver of documentation of informed consent, an additional waiver or modification of HIPAA authorization must also be procured. In these cases, the respective IRB or Ethics Committee can grant the waiver of modification if it is deemed that the following criteria are met: (1) the proposed research could
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not practicably be conducted without the waiver or modification; (2) the proposed research could not practicably be conducted without access to and use of the PHI; (3) the proposed research includes an appropriate plan to protect health information identifiers from improper use or disclosure along with an adequate plan to destroy identifiers at the earliest opportunity absent a health or research justification or legal requirement to retain them, and appropriate written assurances that the PHI will not be used or disclosed to a third party except as required by law, for authorized oversight of the proposed research or for other research uses and disclosures permitted by the Privacy Rule [15]. Although the consent form process for clinical research has a higher level of standardization, some interinstitutional variability remains. In general, however, the process starts with a preliminary meeting at which an individual researcher or a team provides the patient with the informed consent document followed by a run-through and explanation of the document [34]. It is also important to let potential participants know that they are allowed to be joined by another party (family or friend), who can provide support and help the individual keep track of the information being offered. As with the informed consent process for daily clinical practice, the information provided to the potential participant should be put in the context of the individual’s cultural and educational background. Also, the dialogue should be carried out at a pace comfortable for the potential participant, allowing adequate time for the individual to process the information and ask questions. In this context, it is also recommended that other media be employed—e.g., video, audio, interactive media webcasts and podcasts—always keeping the individual’s background in mind [34]. Time is also a factor for a potential participant to process all the information regarding the clinical study, potential procedures, alternatives, and potential benefits and harms. For this reason, the subject should be given a copy of the consent form to take home, so that he or she and potential trusted advisors such as family, friends, counselors, therapists, or patient representatives can discuss the information. Only then can the patient make an informed decision. Every effort should be made by the researchers to be sure that the individual understands the information provided. This can be done by having the subject fill out a written questionnaire, respond to verbal questions, or use a teach-back method in which the individual expresses in his or her own words what the study objectives are, what participation entails, the procedures and treatments being offered, the randomization and blinding process (if applicable according to the study design), the potential benefits and harms, the use of data generated by the trial, and the right to decline participation at any time. As the clinical
Table 4 Suggested information to be included in adequate consent forms for clinical research 1. Research objectives for the clinical triala 2. What is expected from the participant—what will be done and how long he or she is expected to take part 3. Potential benefits (to the individual patient, to the patient population, and to the advancement of science) 4. What is known and not known about the drug or procedure being evaluated 5. Any potential risks to the subject (if known) 6. Whom the subject should contact with questions about or problems with the study 7. Other possible treatment options 8. A clear explanation that the subject has the right to stop participating in the study with no penalty and opt for standard medical care at any time 9. How the subject’s personal information will be protected a
A contact person and phone number for more information should always be provided to the subject at the first meeting
trial goes on, the research team may make new discoveries that could affect your health, well-being, or willingness to remain in the study. Once the study is underway, adaptive designs or protocol amendments to standard designs may warrant changes to the informed consent form, which requires updating the consent form process, in which case all of the same provisions apply, as discussed previously [34]. Table 4 describes the suggested information that adequate consent forms for clinical research should have. As explained before, the main objective is to allow the potential participant to make an informed decision and to be sure that the subject is able to choose freely whether to enroll in (or stay in) the study. When it is a minor undergoing the informed consent process, both parents (or legal guardians) may be required to sign the form for the subject to take part in the clinical trial [42]. The subject should always be provided with a copy of the consent form. The potential participant should also be offered a copy of the study protocol that describes all the details of the clinical trial. According to US regulations, no informed consent document may contain statements that explicitly or tacitly state that the subject would give up (waive) any legal rights. It also may not include any provision releasing (directly or indirectly) the investigator, physician, sponsor, or facility from liability if they are negligent or careless [43]. As can be seen, the informed consent process is an ongoing continuum during which information is presented to individuals to enable them to decide voluntarily whether to participate or continue participation in a research study. As in the case of daily clinical practice, reading and signing the consent form document does not replace active interaction between the investigator and individual deciding to
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World J Surg Table 5 Considerations to keep in mind when initiating the consent process 1. The potential subject’s physical, sociocultural, and mental state should be recognized 2. The consenting process should occur as a time continuum that may include days or weeks to allow time for the individual to consider whether to participate in the study and to discuss the research with his or her trusted advisors 3. It is recommended that the research information and consent document be presented and clarified separately from standard clinical or hospital information. Also, the difference between the conduct of the research and daily clinical practice should be emphasized 4. The participant should always be provided with a copy of the consent form 5. Investigators/members of the team should be available to address any questions or concerns the participant may have during the decision-making process (and certainly during the execution of the trial) 6. A family member or person involved in the care of the participant should be encouraged to participate in the consent process 7. Beyond the standard delivery of complete information about the clinical trial, provision of active methods to evaluate the subject’s level of understanding of the information should be considered 8. Investigators conducting the consent process should ask the subject if he or she has been given adequate time to make a decision and if the consent document and complementary information has been provided in a language they can understand 9. Any and all possibilities for coercion or undue influence should be actively avoided and minimized while providing information about the research and during the consent process
participate. Table 5 presents some important considerations to keep in mind when initiating the consent process. The language and documentation in the consent form— with special emphasis on the research objectives, trial duration, experimental procedures, therapeutic alternatives, and potential harms and benefits—must be written in a culturally appropriate manner and at an intellectual level usually recommended to be at the US school system’s fifth grade reading ability. The written document used for the consent process forms the basis for formal documentation and for the participants’ future reference. As new information about the study becomes available, the consent form should be updated in a timely fashion. The respective IRB or Ethics Committee must then approve of all changes. In the United States, the process of obtaining signed informed consent must comply with the requirements of 45 Code of Federal Regulations 46.116, and the consent form must contain the ‘‘Required Elements of Informed Consent’’ [15]. It is also mandated that informed consent should be obtained in person (no telephone or remote means are allowed) from the participant.
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Table 6 Recommended components for enrollment notes 1. If a pregnancy test is required, results should be reported in the note, describing the sample used (blood or urine), date, and specific results 2. A brief description of the study design should be outlined, including randomization into potential arms, masking level and methods, drugs, devices or procedures evaluated in the study, and the route and length of treatment. If possible, provide the time of first treatment and the tolerance level for such treatment 3. Record who dispensed the study drug (when applicable) and who administered the procedures related to the study (when applicable) 4. If the design calls for the patient to self-administer any study medication or procedure, the treatment provided to the participant for this purpose should be documenteda 5. The fact that no protocol procedures were done prior to consent should be documented. If a test/procedure was done for standard care, it should be so noted 6. A note documenting that the study has been discussed with the patient and that all questions were answered. should be included 7. The contact information for whom to call with questions/ problems related to the study should be included a
Drug administration, dosing and recording, return demonstration of successful administration to patient/family, return of study medication, and if the patient/family has a contact number to call for questions or problems)
For the informed consent form to be considered valid, the following information should be filled out in its entirety: (1) printed full name and signature of person(s) administering the informed consent process, properly dated; (2) printed full name and signature of the research participant (or legal representative), properly dated. However, a signed and dated consent form is not sufficient for adequately documenting the informed consent process. A progress report should be developed and filled out at each encounter that documents the communication between investigator and subject about the research. Such reports should include what was discussed, how every question from the subject was addressed, if the subject received a copy of the consent form to take home, or if the subject signed the consent form. The integration of these reports as a function of time documents the consenting process [34, 35, 42, 43]. At the time of the first encounter for the informed consent process, a written study enrollment note should be included in the patient’s medical record or shadow file. For both inpatient and outpatient studies involving greater than minimal risk, the original signed consent form must be included in the medical record [34, 43]. Table 6 describes recommended components for properly dated and timed enrollment notes. For inpatient or outpatient studies that have aboveminimal risk, the investigator should include the Informed Consent Document in the medical chart [43]. For minimal-
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risk outpatient studies, it is recommended that the investigator put a copy of the informed consent document in the subject’s medical record. Importantly, if the informed consent document is placed in the medical record, it should be indicated in the informed consent document. In addition, the research subject should also be informed if a separate or new medical record will be created because of participation in a research study [34, 42]. In certain instances that have special considerations for confidentiality reasons or clinical research involving sensitive topics, an investigator may wish to refrain from placing a copy of the consent form in the medical record [44]. In such instances, at a minimum the date and time of informed consent should be included along with a note stating that the individual has been enrolled in a research study evaluating a drug or procedure. If the research protocol coup affect the research subject’s health, the statement in the chart must include an adequate description of the intervention required by other health care professionals to deal with any potential medical conditions. Special considerations According to US regulations, ‘‘children’’ are defined as ‘‘persons who have not attained the legal age for consent to treatments or procedures involved in the research under the applicable law of the jurisdiction in which the research will be conducted’’ [45 C.F.R. 46.202(a)] [15]. In most of the United States, the age of adulthood is 18 years unless a person has reached a lower age (depending on the jurisdiction) and has been emancipated by court order, marriage, or active military duty. Thus, in practical terms, persons under 18 years of age are considered ‘‘children’’ for research purposes, and their entry into research requires consent of the parents or legal guardians. Children may not be enrolled in research without ‘‘permission’’ (agreement under standard consent provisions) of a parent or guardian (and of both parents for research of greater than minimal risk, with no prospect of direct benefit to individual subjects, see Section 6.2.1). According to US regulations, a ‘‘guardian’’ is a person ‘‘who is authorized under applicable state or local law to consent on behalf of a child to general medical care’’ [45 C.F.R. 46. 402(e)] [15]. To enroll the child, guardianship papers should be presented. There may be other legal mechanisms of granting permission to a person other than the parent to consent to health care that may suffice as well (e.g., health care power of attorney). The term informed assent describes the process whereby minors may agree to participate in clinical trials. In addition to parental/guardian permission, investigators are required to obtain the ‘‘assent’’ of the child. Assent is ‘‘a
child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent’’ [45 C.F.R. Section 46.402(b)] [15]. Some organizations recommend that assent be obtained from all children age 7 and older] unless the nature of the research dictates otherwise (e.g., research on brain-injured children) [42]. As can be seen, the informed consent document is only one part of the larger process of informed consent that occurs between the potential research participant and members of the research team. The informed consent document should be understandable to the research participants involved.
Discussion Investigators are usually concerned with how to ensure that the consent process provides the appropriate amount of information in a way that the potential participant can adequately understand. Three basic approaches have been described [12]. The ‘‘reasonable physician standard’’ is based on considerations regarding what information a typical physician would provide about a particular treatment or procedure. As this is centered on the physician’s perspective, it is probably not enough because in most cultural and health care contexts the information disclosed by physicians tends to be limited. A second approach, known as the ‘‘reasonable patient/participant standard,’’ is centered on what a usual subject would need to know to make an informed decision regarding a treatment or participation in a clinical study. The ‘‘subjective standard’’ is centered on what a particular individual would need to know and understand to make an informed decision regarding treatment or participation in a clinical study [12]. This standard is challenging to incorporate fully into practice, given that it requires tailoring information for each individual. However, it is also important to consider that placing a focus on the cultural context of the various populations of subjects who could have the indication for a specific treatment or procedure or who could be offered participation in a given clinical trial can help bring an informed consent process based on the ‘‘reasonable patient/ participant standard’’ closer to one based on the ‘‘subjective standard’’ [12]. In addition, the modern day of information sharing and ‘‘big data’’ that could help advance biomedical research in a much more efficient manner calls for consideration of such provisions into the informed consent process [37]. Initial efforts in this area are well underway, and Vanderbilt’s BiuVU ‘‘opt-out’’ process could be a model for further evolution of the informed consent process [39].
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Conclusions The informed consent process consists of a continuous dialogue between research participant and investigator. All measures should be taken to ensure that the concerns and questions from the research subject are properly addressed and there is an adequate level of understanding regarding the research objective and conduct of the study as well as the potential harms and benefits. It is the only way to ensure that the rights of research participants are protected and that the integrity and utility of the informed consent process is maintained.
15.
16.
17.
18. 19.
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