Summary of Draft FDA Guidance
Informed Consent Information Sheet
Guidance for IRBs, Clinical Investigators, and Sponsors
Informed Consent: A Process, Not Just a Signature
The FDA has released a draft guidance on Informed Consent which is being updated for the first time in over 15 years. The commenting period on this draft guidance will remain open until September 14, 2014.
At its core, the draft of the updated guidance emphasizes that the process of informed consent extends beyond a signature on a form. It not only “involves providing a potential subject with adequate information to allow for an informed decision about participation in the clinical investigation” but extends to “facilitating the potential subject’s comprehension of the information.”
Potential subjects must also be provided with adequate opportunities to ask questions - and, this dialogue pathway should remain open throughout the study. The consent process begins during subject recruitment and includes all information provided to potential study participants including recruitment material and dialogue. The informed consent process doesn’t stop once the document is reviewed and signed, but continues throughout the duration of the study for all enrolled patients.
Communication Methods
The Informed Consent Form (ICF) serves several purposes: it is reviewed with the clinical investigator to ensure that subjects receive the appropriate information regarding the clinical trial in which they may be enrolling; it is a reference tool that provides subjects with documented contact information and study information to take home and refer to should they develop additional questions or require further clarification; and it is an official study record that formally documents the subject’s voluntary agreement to participate in the study.
Traditional face-to-face conversations to review paper ICFs are currently the industry standard practice; however, the advancements in new technologies opens up the informed consent process to alternative methods of reviewing and obtaining consent for participation in clinical trials. The Agency recognizes the rapidly changing methods of communication and is interested in alternatives that allow for “adequate exchange of information and documentation” that also ensure that the individual engaging in the informed consent process is either the person who will be enrolling in the clinical investigation or the subject’s legally authorized representative. Examples includes a phone consent interview followed by an exchange of the signed ICF by facsimile. Parties interested in alternative methods of consent are encouraged to contact the FDA, as The Agency is “considering alternative methods using... new technologies and would be interested in comments on these alternative methods.”
Informed Consent Information Sheet
Guidance for IRBs, Clinical Investigators, and Sponsors
Informed Consent: A Process, Not Just a Signature
The FDA has released a draft guidance on Informed Consent which is being updated for the first time in over 15 years. The commenting period on this draft guidance will remain open until September 14, 2014.
At its core, the draft of the updated guidance emphasizes that the process of informed consent extends beyond a signature on a form. It not only “involves providing a potential subject with adequate information to allow for an informed decision about participation in the clinical investigation” but extends to “facilitating the potential subject’s comprehension of the information.”
Potential subjects must also be provided with adequate opportunities to ask questions - and, this dialogue pathway should remain open throughout the study. The consent process begins during subject recruitment and includes all information provided to potential study participants including recruitment material and dialogue. The informed consent process doesn’t stop once the document is reviewed and signed, but continues throughout the duration of the study for all enrolled patients.
Communication Methods
The Informed Consent Form (ICF) serves several purposes: it is reviewed with the clinical investigator to ensure that subjects receive the appropriate information regarding the clinical trial in which they may be enrolling; it is a reference tool that provides subjects with documented contact information and study information to take home and refer to should they develop additional questions or require further clarification; and it is an official study record that formally documents the subject’s voluntary agreement to participate in the study.
Traditional face-to-face conversations to review paper ICFs are currently the industry standard practice; however, the advancements in new technologies opens up the informed consent process to alternative methods of reviewing and obtaining consent for participation in clinical trials. The Agency recognizes the rapidly changing methods of communication and is interested in alternatives that allow for “adequate exchange of information and documentation” that also ensure that the individual engaging in the informed consent process is either the person who will be enrolling in the clinical investigation or the subject’s legally authorized representative. Examples includes a phone consent interview followed by an exchange of the signed ICF by facsimile. Parties interested in alternative methods of consent are encouraged to contact the FDA, as The Agency is “considering alternative methods using... new technologies and would be interested in comments on these alternative methods.”
Patient Risk Versus Benefit
Regardless of the method of reviewing and obtaining consent, the content must be clear. The risk of coercion and undue influence plays a prominent role in the updates The Agency has made to the draft of this guidance. The Belmont Report differentiates between the two as follows: “Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance. Undue influence, by contrast, occurs through an offer of an excessive, unwarranted, inappropriate, or improper reward or other overture in order to obtain compliance.”
Statements that claim investigational test articles are safe or effective for the purposes for which they are being investigated are prohibited. Careful wording is essential in the development of the ICF in order to avoid overstating potential benefits that may contribute to a subject’s therapeutic misconception. In particular, since the FDA does not formally approve Investigational New Drug Applications, statements such as “The FDA has given permission for the clinical investigation to proceed” or “FDA has approved the clinical investigation” should be avoided.
In addition to providing a clear, understandable description of the clinical investigation, an exhaustive list of risks and discomforts and benefits to the patient as well as future patient populations needs to be provided in the informed consent process. A new provision in this draft of the guidance explains that patients must also be informed of “the care they would likely receive if they choose not to participate in research.” This should highlight the current medically recognized standard of care for their condition, “other forms of therapy and, when appropriate, supportive care with no disease-directed therapy.” If appropriate, the subject can also be referred to a healthcare professional who is better able to outline these standard and medically accepted alternative treatments. Similarly, the consent process should be designed to inform subjects of the consequences of withdrawal from the clinical investigation.
Responsibilities
The FDA has greatly expanded the explanation of responsibilities regarding the informed consent process. The responsibilities are separated into four parties: the Investigational Review Board (IRB), the Clinical Investigator, the Sponsor, and the FDA.
All information that is provided to subjects as part of a clinical investigation must be reviewed and approved by the IRB prior to use. The IRB is responsible for ensuring that “the consent process minimizes the possibility of coercion and undue influence.”
It is the responsibility of the Clinical Investigator to protect the rights, safety and welfare of subjects during a clinical investigation and to ensure that legally effective informed consent is obtained from each subject before he or she takes part in a clinical investigation. Regardless of whether the Investigator performs the consent interview or delegates the responsibility to a qualified individual, the Investigator is ultimately responsible for ensuring the clinical investigation is conducted according to applicable FDA regulations.
The sponsor is responsible for managing the overall development of the content included in the ICF and for incorporating, where applicable, individual site considerations for multicenter clinical investigations to ensure that the ICF is truthful for each participating site.
The FDA may ask to review the informed consent form (ICF) prior to issuing an Investigational New Drug (IND), but the ICF is not currently required as part of an IND. For an Investigational Medial Device, however, all forms and informational materials that will be provided to subjects to obtain informed consent should be submitted along with the Investigational Device Exemption (IDE) application to ensure clarity of the material content. Ultimately, the review and approval of the informed consent process is the responsibility of the IRB.
Additional Considerations
The Agency also addresses several other considerations in the revised guidance. These considerations are primarily focused on the study population and management of patient data and records. In regard to study populations, the FDA is focused particularly on those considered to be vulnerable to the consenting process. Among these groups, they’ve highlighted non-English speaking subjects and pediatric subjects.
According to the US census bureau report in 2011, it is estimated that approximately 7% of the US population does not speak English. In the updated guidance, The Agency goes into depth on his topic explaining that the Investigators and IRBs involved in clinical investigations must “consider the ethical ramifications of enrolling or excluding potential subjects when a language barrier may exist between the investigator(s) and some or all of the potential subjects.” When individuals with minimal English comprehension are enrolled in studies, the IRB and the Investigator must provide the consent information in a language that is understandable.
The Agency also specifically addresses the pediatric population. FDA has already demonstrated the need for the development of products to treat pediatric diseases and illness through the Pediatric Research Equity Act of 2007 (PREA) and Best Pharmaceuticals for Children Act of 2007 (BPCA), which have resulted in an increased number of studies being conducted in this population. Based on a recent search of ClinicalTrials.gov, since January of 2014 over 1000 studies in pediatric populations have been initiated. This accounts for 18% of all studies initiated in 2014 thus far that are listed on ClinicalTrials.gov. While the process of assent of children has been industry standard, it is explicitly included in the revised draft guidance.
The Agency also addresses several other considerations in the revised guidance. These considerations are primarily focused on the study population and management of patient data and records. In regard to study populations, the FDA is focused particularly on those considered to be vulnerable to the consenting process. Among these groups, they’ve highlighted non-English speaking subjects and pediatric subjects.
According to the US census bureau report in 2011, it is estimated that approximately 7% of the US population does not speak English. In the updated guidance, The Agency goes into depth on his topic explaining that the Investigators and IRBs involved in clinical investigations must “consider the ethical ramifications of enrolling or excluding potential subjects when a language barrier may exist between the investigator(s) and some or all of the potential subjects.” When individuals with minimal English comprehension are enrolled in studies, the IRB and the Investigator must provide the consent information in a language that is understandable.
The Agency also specifically addresses the pediatric population. FDA has already demonstrated the need for the development of products to treat pediatric diseases and illness through the Pediatric Research Equity Act of 2007 (PREA) and Best Pharmaceuticals for Children Act of 2007 (BPCA), which have resulted in an increased number of studies being conducted in this population. Based on a recent search of ClinicalTrials.gov, since January of 2014 over 1000 studies in pediatric populations have been initiated. This accounts for 18% of all studies initiated in 2014 thus far that are listed on ClinicalTrials.gov. While the process of assent of children has been industry standard, it is explicitly included in the revised draft guidance.
Review of patient records is also at the forefront of this draft guidance. The guidance
focuses on making a clear differentiation between reviews of patient records for the
purposes of patient screening prior to enrollment and reviews of patient records to
determine study feasibility at the site. While it must comply with HIPAA, a review of
patient information may be conducted prior to patient recruitment to evaluate the
patient population at a particular site without informed consent from the patients;
however, only information to establish the patient’s eligibility for the study and
contact information should be recorded. The subject must be informed that his or her
records will be reviewed during the informed consent process before such a review is
conducted.
Another component that is outlined in this draft guidance pertains to data generated as part of the clinical investigation. Study subjects have a right to withdraw from the clinical investigation, but any data generated as part of the investigation may not be removed from the study database; this must be properly communicated during the informed consent process.
Conclusion
In the revised draft guidance, FDA makes it clear that informed consent is not just a signature, but rather a process that is carried through the entire study duration beginning during recruitment and continuing until the end of the clinical investigation. The informed consent process aims to protect patients from coercion and misinformation while ensuring that they are informed of risks and benefits of the investigation prior to participation. It serves to protect patient information while allowing the investigation to collect necessary data. Informed consent is the responsibility of all parties involved: FDA, the IRB, the Investigator, and the Sponsor.
A successful and thorough informed consent process will leverage resources from each of these parties to ensure patient safety and investigational success while being cognizant of vulnerable patient populations and the utilization of patient medical records.
Another component that is outlined in this draft guidance pertains to data generated as part of the clinical investigation. Study subjects have a right to withdraw from the clinical investigation, but any data generated as part of the investigation may not be removed from the study database; this must be properly communicated during the informed consent process.
Conclusion
In the revised draft guidance, FDA makes it clear that informed consent is not just a signature, but rather a process that is carried through the entire study duration beginning during recruitment and continuing until the end of the clinical investigation. The informed consent process aims to protect patients from coercion and misinformation while ensuring that they are informed of risks and benefits of the investigation prior to participation. It serves to protect patient information while allowing the investigation to collect necessary data. Informed consent is the responsibility of all parties involved: FDA, the IRB, the Investigator, and the Sponsor.
A successful and thorough informed consent process will leverage resources from each of these parties to ensure patient safety and investigational success while being cognizant of vulnerable patient populations and the utilization of patient medical records.