Differences between ICH E6 guidelines and FDA regulations Flashcards
Differences in obtaining a statement from the IRB that it is organized and operates according to GCP and applicable laws and regulations
ICH E6 Section 5.11 requires that “the sponsor obtain from the investigator/institution . . .[a] statement obtained from the IRB/IEC that it is organized and operates according to GCP and the applicable laws and regulations.” Sponsors may approach IRBs directly to obtain this statement, but some sponsors request that the investigator obtain the statement from the IRB and then forward it to the sponsor.
Differences in confidentiality of medical records
ICH requires that informed consent should indicate that everybody in the study has direct access to the participant’s records, and that the sponsor should verify that each subject has consented to this.
FDA says that the consent only needs a statement describing the extent of confidentiality, and that the FDA may inspect the records.
Differences in investigator responsibility
FDA requires that the investigator provide Form FDA 1572 to the FDA, ICH does not
ICH addresses medical care of subjects and requires a qualified physician or dentist to be responsible for trial-related medical decisions. The FDA does not require this
ICH requires that the investigator maintain source docs and trial records. Source data should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data should be traceable, should not obscure the original entry, and should be explained if necessary.
Differences in sponsor responsibility
ICH requires the sponsor to have a system to manage quality throughout all stages of the trial process. The system should use a risk-based approach including identification of study risks to determine which may safely be omitted from continual monitoring.
ICH and FDA both allow the sponsor to delegate responsibilities to a CRO. ICH requires the sponsor ensure oversight, FDA is okay with a general statement that obligations are transferred.
ICH and FDA agree that sponsor is responsible for trial management, data handling, and record keeping. ICH ALSO requires the sponsor to make sure that electronic data handling/systems conform to sponsor’s established requirements for completeness, accuracy, reliability, and are validated and that sponsors maintain SOPs for these systems.
ICH requires the sponsor to take prompt action to secure compliance when noncompliance with the protocol, SOPs, GCP, and/or applicable regulatory requirements is discovered. ICH E6 further requires the sponsor to perform a root cause analysis and implement an appropriate corrective and preventative action depending on the significance of the noncompliance. Also, ICH E6 states that if the sponsor identifies continuing and/or serious noncompliance, the sponsor should end the investigator’s/institution’s participation in the clinical trial and notify regulatory authorities.
Who placed the responsibility of selecting qualified investigators with the sponsor?
Both the FDA and ICH
Who says the sponsor is responsible for monitoring the study?
Both the FDA and ICH
Differences in sponsor monitoring
ICH states that the sponsor should develop a risk-based approach to monitoring, choose the monitoring strategy, and document the rationale for choosing the strategy. Monitor must submit written reports to the sponsor and the sponsor must document monitoring results. ICH also requires sponsors to develop a monitoring plan tailored to the specific human subject protection and data integrity risks of the trial.
FDA regulations in 21 CFR 312 only state the sponsor is responsible for ensuring proper monitoring of the investigation.
How long does the ICH require the sponsor retain essential documents for after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region?
At least 2 years
Differences in signature by person conducting the consent discussion?
ICH requires that the consent should be signed and dated by subject/LAR and by the person who conducted the informed consent discussion. FDA only requires the signature of the subject and the date the subject signed.
Differences in subject receiving a consent form
ICH requires the subject/LAR receive a copy of the signed and dates ICF, FDA allows subjects to get a signed or an unsigned copy.
Differences in assent of children and adult with cognitive impairments
ICH requires that children and incapacitated adults assent to research if possible, HHS and FDA regulations only require that children assent, neither specify that incapacitated adults assent.
Differences in impartial witnesses for illiterate subjects
ICH requires one if the subject/LAR is unable to read, and the witness should sign and date the ICF. FDA only requires that the ICF is read to the subject or a SF consent document and a written oral presentation be used
Differences in requirements for emergency situations
ICH requires that informed consent should always be requested, and if this is impossible in an emergency situation then the subject/LAR should be told ASAP and consent to continue should be requested.
FDA provides exception to informed consent in emergency research or in a life-threatening situation where it is necessary, the subject cannot consent and there is no time to obtain consent, no alternative exists, and the IRB is informed within 5 days.
Differences in elements of consent
ICH requires explanation of alternative treatments available and their risks/benefits.
FDA requires that the consent form explain that the study is research, explanation of the research/purposes/duration/descriptions and say what part is experimental. ICH requires all this and ALSO a description of each arm of the study in the consent form, and the likelihood of receiving each of the study arms.
ICH requires explanation of the subjects responsibilities in the ICF, FDA does not
ICH requires explanation of potential benefits in the ICF
ICH requires that prorated payment be included in ICF, and the IRB should review amount and method to avoid coercion or undue influence. FDA does not require
ICH addresses non-therapeutic research
ICH recommends the investigator inform subjects primary physician about the subjects participation if the subject consents. FDA does not address this.
Differences in IRB responsibilities
ICH lists documents the IRB should review, FDA only requires IRB review the ICF and keep copies of research proposals, scientific evaluations, sample consent docs
ICH and FDA (21 CFR 56) both state that the IRB/IEC should retain all relevant records for three (3) years after completion of the trial.
ICH requires the IRB reviews any protocol deviations, investigators must document and explain deviations. ICH requires documented approval of protocol and amendments. FDA requires review of amendments, but not review of deviations.
FDA has issued guidance that an IRB can approve a waiver or alteration of consent if there is no more than minimal risk, this doesn’t affect the rights of subjects, the waiver or alteration is needed, and participants get appropriate pertinent info after participation. ICH does not include provisions for waiving or altering consent.
