Additional Regulatory Requirements

Participant Withdrawal:

1. Clarification of Withdrawal Intent:
   • When a participant decides to withdraw from a clinical trial, the investigator should ask whether the participant wishes to withdraw from all components of the trial or only from the primary interventional component.
   • If the participant only withdraws from the primary interventional component, research activities involving other components, such as follow-up data collection, may continue with the participant's previously given consent.
   • The investigator should explain to the participant the importance of obtaining follow-up safety data.
2. Retention and Analysis of Collected Data:
   • Investigators are allowed to retain and analyze already collected data from participants who withdraw or whose participation is terminated by an investigator, provided such analysis falls within the scope described in the IRB-approved protocol.
   • This applies even if the data includes identifiable private information.
3. Destruction or Exclusion of Data (Non-FDA Regulated Research):
   • For research not subject to FDA regulation, investigators, in consultation with the funding agency, can choose to honor a participant’s request to destroy or exclude their data from analysis.
4. Informed Consent and Data Retention:
   • Investigators should explain during the informed consent process whether already collected data will be retained and analyzed even if the participant chooses to withdraw from the research.

When research is covered by a certificate of confidentiality, researchers:

1. Disclosure Restrictions:
   • Researchers may not disclose or provide, in any Federal, State, or local civil, criminal, administrative, legislative, or other proceeding, the name of an individual or any information, document, or biospecimen containing identifiable, sensitive information created or compiled for the research without the individual's consent.
   • Researchers may not disclose or provide this information to any person not connected with the research.
2. Permissible Disclosures:
   • Disclosure is allowed when:
     • It is required by Federal, State, or local laws (excluding civil, criminal, administrative, legislative, or other proceedings).
     • It is necessary for the medical treatment of the individual and made with their consent.
     • It is made with the consent of the individual.
     • It is made for other scientific research in compliance with applicable Federal regulations governing the protection of human participants in research.

3.     Limitations:

• Researchers must inform participants of the protections and limitations of certificates of confidentiality.
  • For studies previously issued a Certificate, NIH does not expect participants to be notified of changes in protections, unless determined appropriate by the IRB.
  • Participants in the study cohort recruited prior to issuing a Certificate and are no longer active are not expected to be notified of the Certificate or changes in protections, unless determined appropriate by the IRB.

4. Compliance by Other Researchers:
   • Researchers conducting research covered by a certificate of confidentiality, even if not federally funded, must ensure that other researchers or organizations comply with applicable requirements if identifiable, sensitive information is provided to them when research is covered by a certificate of confidentiality.

Verification of Electronic Signatures:

The regulation 21 CFR part 11 indeed mandates the verification of an individual's identity before using their electronic signature for consent forms during electronic, digital, or remote consent processes. This is to ensure the authenticity and integrity of the electronic signatures.

Participant Withdrawal:

• Data Retention: Data collected up to the point of withdrawal should remain part of the study database and cannot be removed. This aligns with maintaining the integrity of the data collected during the participant's involvement.
• Continued Follow-Up: Investigators are permitted to ask participants who withdraw if they are willing to provide continued follow-up. This follow-up might involve collecting additional data on clinical outcomes, which must be distinguished from study-related interventions. The privacy and confidentiality of the participant’s information must be safeguarded.
• Informed Consent for Continued Follow-Up: If continued follow-up is not covered in the original consent form, the investigator must obtain informed consent for this additional participation. This requires IRB approval if it involves modifying the consent form or adding new elements not initially covered.
• Access Restrictions: If a participant withdraws and does not consent to continued follow-up, investigators must refrain from accessing the participant’s medical or other confidential records related to the study. This ensures respect for the participant’s withdrawal and privacy.

Review of Pre-Withdrawal Data: Investigators may review and use data collected before withdrawal and may consult public records, such as those establishing survival status. This is permissible to ensure the study's results

1. FDA Restrictions on Promotion: Investigators and their representatives must adhere to FDA restrictions on the promotion of investigational drugs, meaning that they are prohibited from making any promotional claims that suggest the investigational new drug is safe or effective for the purposes for which it is under investigation; this restriction is in place to prevent the commercial promotion of the drug before it has been officially approved for commercial distribution, although it does not limit the full exchange of scientific information or the dissemination of findings through scientific or lay media. Moreover, investigators are strictly prohibited from commercially distributing or test marketing the investigational new drug.
2. General Responsibilities of Investigators: Investigators are required to ensure that the investigation is conducted in accordance with the signed investigator statement, the investigational plan, and applicable regulations; they must also protect the rights, safety, and welfare of participants under their care and manage the investigational drugs properly. Additionally, in compliance with 21 CFR §50, investigators must obtain the informed consent of each participant before administering the drug, unless exceptions provided in 21 CFR §50.23 or §50.24 apply. Specific responsibilities are further detailed in 21 CFR §50 and §56.
3. Control of Investigational Drugs: The investigational drug must be administered solely under the personal supervision of the investigator or a sub-investigator who is responsible to the main investigator; furthermore, the drug must not be supplied to individuals who are not authorized to receive it under the regulations stipulated.
4. Recordkeeping and Record Retention: Investigators must maintain detailed records of the drug’s disposition, including dates, quantities, and participant usage, and if the investigation is terminated, suspended, discontinued, or completed, they are required to return unused drug supplies to the sponsor or otherwise dispose of them in accordance with 21 CFR §312.59. Additionally, investigators must prepare and maintain accurate case histories for each participant, documenting all relevant observations and data, including signed consent forms and medical records; these records must confirm that informed consent was obtained prior to participation. Required records must be retained for 2 years after the date a marketing application is approved for the drug or, if no application is filed or if it is not approved, until 2 years after the investigation is discontinued and FDA is notified.
5. Investigator Reports: Investigators are obligated to submit all progress reports to the sponsor, who is responsible for collecting and evaluating the results; they must promptly report any adverse effects that might reasonably be attributed to the drug, with immediate reporting required for serious adverse effects. Upon completing their participation in the investigation, investigators must provide the sponsor with a comprehensive final report. Furthermore, investigators must disclose sufficient financial information to the sponsor to facilitate accurate certification or disclosure statements as required by 21 CFR §54, with prompt updates to this information if relevant changes occur during the study and for 1 year following its completion.
6. Assurance of IRB Review: Investigators must ensure that an IRB, compliant with the requirements outlined in 21 CFR §56, will be responsible for the initial and ongoing review and approval of the clinical study; they are also required to report all research activity changes and unanticipated problems involving risk to human participants or others to the IRB promptly, and must not make changes to the research without IRB approval, except when necessary to eliminate immediate hazards to participants.
7. Inspection of Records and Reports: Investigators must allow authorized FDA officers or employees reasonable access to inspect, copy, and verify any records or reports related to the study as mandated by 21 CFR §312.62; however, they are not obliged to divulge participant names unless the records necessitate a detailed case study or there is reason to suspect the records do not reflect actual case studies or results.
8. Handling Controlled Substances: If the investigational drug falls under the Controlled Substances Act, investigators must implement adequate security measures, including storing the drug in a securely locked, substantially constructed cabinet or enclosure with limited access, to prevent theft or diversion into illegal distribution channels.

1. General Responsibilities of Investigators:

• Investigators must ensure that the investigation is conducted according to the signed agreement, the investigational plan, and applicable FDA regulations. They are responsible for protecting the rights, safety, and welfare of participants under their care and for managing the investigational devices. Additionally, informed consent must be obtained in compliance with 21 CFR §50.

2. Specific Responsibilities of Investigators:

• Awaiting Approval: Investigators may assess potential participant interest but must not request written informed consent or allow participation until IRB and FDA approvals are obtained.
• Compliance: Investigators must conduct the investigation in line with the signed agreement, investigational plan, and applicable FDA regulations, including any conditions imposed by the IRB or FDA.
• Supervising Device Use: Devices must only be used under the investigator's supervision, and investigators must not supply the device to unauthorized individuals.
• Financial Disclosure: Investigators must provide the sponsor with accurate financial information for certification or disclosure statements required under 21 CFR §54 and update this information promptly during and up to 1 year after the study's completion.
• Disposing of Device: Upon completion or termination of the investigation or at the sponsor’s request, investigators must return any remaining device supplies to the sponsor or dispose of them as directed.

3. Recordkeeping:

• Correspondence: Maintain all correspondence with investigators, IRBs, sponsors, monitors, or FDA, including required reports.
• Device Records: Document receipt, use, or disposition of the device, including type, quantity, receipt dates, batch numbers, and names of those who received, used, or disposed of the device; record reasons for return, repair, or disposal of the device.
• Case Histories: Maintain case report forms and supporting data, including signed consent forms, medical records, and documentation of informed consent; include records of adverse device effects, participant condition upon entry and throughout the investigation, and exposure details (dates, times, and other therapies).
• Protocol Deviations: Keep the protocol and documents showing dates and reasons for deviations.
• Additional Records: Retain any other records required by FDA regulations or specific to the investigation.

4. Inspections:

• Entry and Inspection: Allow FDA employees access to inspect any establishment where devices are held, including manufacturing or processing sites.
• Records Inspection: Permit FDA employees to inspect and copy all records related to the investigation.
• Records Identifying Participants: If the FDA suspects inadequate informed consent or incomplete reports, investigators must allow inspection of records identifying participants.

5. Reports:

• Unanticipated Adverse Device Effects: Report to the sponsor and IRB within 10 working days of learning about the effect.
• Withdrawal of IRB Approval: Report IRB withdrawal of approval within 5 working days.
• Progress Reports: Submit progress reports to the sponsor, monitor, and IRB at least annually.
• Deviations: Notify the sponsor and IRB of deviations made in emergencies within 5 working days. For other deviations, obtain prior approval from the sponsor, and if they affect scientific soundness or participant welfare, from the FDA and IRB.
• Informed Consent: Report any use of a device without informed consent to the sponsor and IRB within 5 working days.
• Final Report: Submit a final report to the sponsor and IRB within 3 months after study completion or termination.
• Other Information: Provide accurate, complete, and current information about any aspect of the investigation upon request from IRB or FDA.

1. GDPR Applicability: Data and/or specimen collection involving personal data about individuals located in (but not necessarily citizens of) European Union member states, Norway, Iceland, Liechtenstein, and Switzerland is subject to EU General Data Protection Regulations. Researchers must ensure compliance with these regulations.
2. Prospective Data Collection: For all prospective data and/or specimen collection activities subject to EU GDPR, consult institutional legal counsel or the institution’s Data Protection Officer to confirm that the following elements are consistent with institutional policies and GDPR interpretations:
   • Study design elements related to data security measures.
   • Procedures for the rights to access, rectification, and erasure of data.
   • Procedures for broad/unspecified future use consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens.
3. Retrospective Data Collection: For retrospective data and/or specimen collection activities subject to EU GDPR, submit data use agreements through the Agreements system to ensure consistency with institutional policies and GDPR interpretations:
   • Study design elements related to data security measures.
   • Procedures for the rights to access, rectification, and erasure of data.
   • Procedures for broad/unspecified future use consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens.
4. Regulatory Consistency: When FDA or DHHS regulations apply in addition to EU GDPR regulations, ensure that procedures related to withdrawal from the research, as well as the management of information and biospecimens, remain consistent with the applicable regulations and procedures.

The NIH issued its Notice of Changes to NIH Policy for Issuing Certificates of Confidentiality (CoCs) to protect sensitive, identifiable information from legal disclosure. Effective October 1, 2017, CoCs are automatically issued for applicable NIH awards, and the award serves as confirmation of CoC protections. Also, NIH will no longer provide a paper certificate. The award itself may be used as confirmation that CoC protections are in place. The policy applies to research commenced or ongoing on or after December 13, 2016. For ongoing studies, re-consenting participants is generally not required, but IRBs may choose to inform participants about changes in protection. The NIH CoC website has now been updated and includes updated consent language and FAQs.

Although CoCs are intended to prohibit the disclosure of sensitive, identifiable information in response to legal demands, applicability has been broadened to include the following:

• Human subjects research as defined in the Federal Policy for the Protection of Human Subjects (45 CFR 46), including exempt research except for human subjects research that is determined to be exempt from all or some of the requirements of 45 CFR 46 if the information obtained is recorded in such a manner that human subjects cannot be identified or the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;
• Research involving the collection or use of biospecimens that are identifiable to an individual or for which there is at least a very small risk that some combination of the biospecimen, a request for the biospecimen, and other available data sources could be used to deduce the identity of an individual;
• Research that involves the generation of individual level, human genomic data from biospecimens, or the use of such data, regardless of whether the data is recorded in such a manner that human subjects can be identified or the identity of the human subjects can readily be ascertained as defined in the Federal Policy for the Protection of Human Subjects (45 CFR 46); or
• Any other research that involves information about an individual for which there is at least a very small risk, as determined by current scientific practices or statistical methods, that some combination of the information, a request for the information, and other available data sources could be used to deduce the identity of an individual, as defined in subsection 301(d) of the Public Health Service Act.

Institutions and investigators can also send questions to: NIH CoC Coordinator.

For more information see, Appendix:  Federal Agencies that issue Certificates of Confidentiality

The National Institutes of Health (NIH) has issued the final NIH Policy for Data Management and Sharing (DMS Policy) to promote the management and sharing of scientific data generated from NIH-funded or conducted research. This Policy is effective January 25, 2023, and applies to research funded or conducted by NIH that results in the generation of scientific data. The DMS policy establishes the requirements to submit Data Management and Sharing Plans to the NIH. Investigators are responsible for adherence to their plans and referring to the NIH for the latest guidance and policy changes.

Policy Impact on IRB Submissions

As part of the criteria for IRB approval outlined in federal regulations, the IRB must confirm that informed consent has been sought from participants and that there are adequate provisions to maintain the confidentiality of data. Hence, this policy has an impact on confidentiality plans and informed consent submitted to the IRB.

Data Management and Sharing Plans should be submitted to the IRB so that the IRB may review plans for data sharing, along with measures of security, confidentiality, and any limitations to data sharing.

• Data Management and Sharing Plans should align with the confidentiality plan outlined in the standalone protocol.
• The NIH emphasizes that “access to scientific data derived from humans should be controlled, even if de-identified and lacking explicit limitations on subsequent use.” Additionally, controlled-access repositories should be considered if the data “could be considered sensitive, such as including information regarding potentially stigmatizing traits, illegal behaviors, or other information that could be perceived as causing group harm or used for discriminatory purposes.”
• Likewise, “privacy protections should be considered regardless of whether the data meet technical and/or legal definitions of “de-identified” and can legally be shared without additional protections.”
• Questions on NIH requirements for Data Management and Sharing Plans should be directed to the IRB.

Data sharing and use should be communicated in consent processes. The NIH encourages researchers to “develop robust consent processes that prioritize clarity regarding future sharing and use of scientific data, including limitations on future use, and general aspects regarding how data will be managed.” Likewise, “scientific data that are collected, shared, or used without informed consent also deserve privacy considerations.”

• Investigators should ensure that their Data Management and Sharing Plans align with what is presented as part of the informed consent process. This ensures that participants’ autonomy is respected.
• NIH recommends that “scientific data be de-identified to the greatest extent that maintains sufficient scientific utility. Unless participants explicitly consent to share identifiable data (e.g., under the broad consent provision of the Common Rule), data should generally be shared only in a de-identified format.”

The NIH Single IRB (sIRB) Policy, effective January 25, 2018, requires all participating sites in multi-site studies involving non-exempt human subjects research funded by NIH to use a single IRB to conduct ethical reviews. A single IRB of record will be designated to review and approve the research, ensuring the protection of human subjects across all participating sites. This policy aims to streamline the review process, reduce administrative burdens, and enhance efficiency while ensuring the protection of human subjects. The policy applies to domestic sites conducting the same research protocol under NIH funding, excluding career development, research training, and fellowship awards. By centralizing the review process with a single IRB, the NIH seeks to maintain high standards of human subjects protection while minimizing redundant efforts across multiple sites. The NIH single IRB policy applies to multi-site human subjects research regardless of the funding mechanism (e.g., grants, cooperative agreements, contracts, or other mechanisms such as Cooperative Research and Development Agreements (CRADAs), and Interagency Agreements (IAA)). The policy applies whether the sites are subawards to a primary award recipient or separate awards are made for participating sites. The NIH Single IRB policy does not apply to Other Transaction Agreements (OTAs). UMassD has established procedures for selecting and working with sIRBs. Researchers should contact the IRB for guidance on sIRB selection and reliance agreements.

Key Points 

• Responsibilities of the Lead Institution: The lead institution (the one applying for the NIH grant) selects the sIRB based on its capability to provide appropriate review and compliance. The lead institution must establish an IRB Review Agreement with the sIRB, detailing the review process, communication procedures, and handling of modifications or reports.
• Responsibilities of Participating Sites: Local Context must be provided for each site to address local regulatory issues and obtain any additional approvals or consents required. Sites must enter into a Reliance Agreement with the lead institution and the sIRB, formalizing reliance on the sIRB and outlining site responsibilities.
• Coordination: The lead institution and participating sites must coordinate with the sIRB to provide the required information and address issues promptly. The sIRB provides ongoing oversight, while the lead institution and sites must report adverse events, protocol deviations, and significant issues as specified in the IRB Review Agreement.
• Exceptions: Exceptions to the sIRB policy may apply in cases involving sensitive populations or site-specific concerns. Justification and NIH approval are required for exceptions.

ICH-GCP refers to the guidelines established by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)  to ensure the quality and integrity of clinical trials. ICH-GCP, or Good Clinical Practice, is a set of internationally recognized standards for conducting clinical trials involving human participants.

1. Investigator's Qualifications and Agreements:
   • The clinical trial should be conducted in accordance with the ethical principles originating from the Declaration of Helsinki, aligned with good clinical practice (GCP) and applicable regulatory requirements.
   • The investigator should be qualified by education, training, and experience to assume responsibility for the trial's proper conduct; they must meet all qualifications specified by regulatory requirements and provide evidence of such qualifications through up-to-date curriculum vitae and/or other relevant documentation requested by the sponsor, the IRB, or regulatory authorities.
   • The investigator should be thoroughly familiar with the appropriate use of the investigational product as described in the protocol, the current Investigator's Brochure, product information, and other sources provided by the sponsor.
   • The investigator should be aware of and comply with GCP and applicable regulatory requirements, including ICH-GCP training.
   • The investigator/institution should permit monitoring and auditing by the sponsor and inspection by appropriate regulatory authorities. f. The investigator should maintain a list of appropriately qualified persons to whom significant trial-related duties have been delegated.
2. Adequate Resources:
   • The investigator should demonstrate a potential for recruiting the required number of suitable participants within the agreed recruitment period, based on retrospective data if necessary.
   • The investigator should have sufficient time to properly conduct and complete the trial within the agreed trial period.
   • The investigator should have an adequate number of qualified staff and facilities available for the duration of the trial to conduct it properly and safely.
   • The investigator should ensure that all persons assisting with the trial are adequately informed about the protocol, the investigational product, and their trial-related duties and functions.
3. Medical Care of Trial Participants:
   • A qualified physician (or dentist, when appropriate), who is an investigator or a sub-investigator for the trial, should be responsible for all trial-related medical (or dental) decisions.
   • During and following a participant's involvement in the trial, the investigator/institution should ensure that adequate medical care is provided for any adverse events, including clinically significant laboratory values related to the trial. The investigator/institution should inform participants when medical care is needed for intercurrent illnesses of which the investigator becomes aware.
   • It is recommended that the investigator inform the participant's primary physician about the participant's trial participation if the participant has a primary physician and agrees to the primary physician being informed.
   • Although a participant is not required to provide reasons for withdrawing prematurely from the trial, the investigator should make a reasonable effort to ascertain the reasons while fully respecting the participant's rights.
4. Communication with IRB:
   • Before initiating a trial, the investigator/institution should have written and dated approval from the IRB for the trial protocol, written informed consent form, consent form updates, participant recruitment procedures (e.g., advertisements), and any other written information to be provided to participants.
   • As part of the investigator's/institution’s written application to the IRB, the investigator/institution should provide a current copy of the Investigator's Brochure. If the Investigator's Brochure is updated during the trial, the investigator/institution should supply a copy of the updated Investigator’s Brochure to the IRB.
   • During the trial, the investigator/institution should provide the IRB with all documents pertinent to review.
5. Compliance with Protocol:
   • The investigator/institution should conduct the trial in compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authorities and which was given approval by the IRB. The investigator/institution and the sponsor should sign the protocol or an alternative contract to confirm the agreement.
   • The investigator should be able to demonstrate, based on retrospective data, if necessary, the potential for recruiting the required number of suitable participants within the agreed recruitment period.
   • The investigator should have enough qualified staff and facilities available for the foreseen duration of the trial to conduct it properly and safely.
   • During and following a participant's participation in the trial, the investigator/institution should ensure that adequate medical care is provided for any adverse events, including clinically significant laboratory values related to the trial. The investigator/institution should inform a participant when medical care is needed for intercurrent illnesses of which the investigator becomes aware.
   • The investigator should not implement any deviation from or changes to the protocol without agreement from the sponsor and prior review and documented approval by the IRB of an amendment, except where necessary to eliminate immediate hazards to trial participants or when the changes involve only logistical or administrative aspects of the trial (e.g., change in monitors, change of telephone numbers).
6. The investigator, or person designated by the investigator, should document and explain any deviation from the approved protocol. The investigator may implement a deviation from or change to the protocol to eliminate an immediate hazard to trial participants without prior IRB approval. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendments should be submitted:
   • • to the IRB for review and approval,
     • to the sponsor for agreement, and, if required,
     • to the regulatory authorities.
7. Investigational Product:
   • Responsibility for investigational product accountability at the trial site rests with the investigator/institution.
   • Where allowed or required, the investigator/institution may assign some or all their duties for investigational product accountability at the trial site to an appropriate pharmacist or another suitable individual under their supervision.
   • The investigator/institution and/or a designated pharmacist or appropriate individual should maintain records of the product's delivery to the trial site, inventory at the site, use by each participant, and return to the sponsor or alternative disposition of the unused product. These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the unique code numbers assigned to the investigational product and trial participants. Investigators should maintain records that adequately document that participants were provided the doses specified by the protocol and reconcile all investigational products received from the sponsor.
   • The investigational product should be stored as specified by the sponsor and in accordance with applicable regulatory requirements.
   • The investigator should ensure that the investigational product is used only in accordance with the approved protocol.
   • The investigator, or a person designated by the investigator/institution, should explain the correct use of the investigational product to each participant and check at appropriate intervals that each participant is following the instructions properly.
   • Randomization Procedures and Unblinding: The investigator should follow the trial's randomization procedures, if any, and ensure that the code is broken only in accordance with the protocol. If the trial is blinded, the investigator should promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product.
8. Informed Consent of Trial Participants
   • In obtaining and documenting informed consent, the investigator should comply with the applicable regulatory requirements and should adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki. Before the trial begins, the investigator should have the IRB's written approval opinion of the written informed consent form and any other written information to be provided to participants.
   • The written informed consent form and any other written information to be provided to participants should be revised whenever important new information becomes available that may be relevant to the participant’s consent. Any revised written informed consent form, and written information should receive the IRB's approval opinion in advance of use. The participant or their legally acceptable representative should be informed promptly if new information becomes available relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented.
   • Neither the investigator, nor the trial staff, should coerce or unduly influence a participant to participate or to continue to participate in a trial.
   • None of the oral and written information concerning the trial, including the written informed consent form, should contain any language that causes the participant or the participant's legally acceptable representative to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence.
   • The investigator, or a person designated by the investigator, should fully inform the participant or, if the participant is unable to provide informed consent, the participant's legally acceptable representative, of all pertinent aspects of the trial including the written information and the approval opinion by the IRB.
   • The language used in the oral and written information about the trial, including the written informed consent form, should be as non-technical as practical and should be understandable to the participant or the participant's legally acceptable representative and the impartial witness, where applicable.
   • Before informed consent may be obtained, the investigator, or a person designated by the investigator, should provide the participant or the participant's legally acceptable representative ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial should be answered to the satisfaction of the participant or the participant's legally acceptable representative.
   • Prior to a participant’s participation in the trial, the written informed consent form should be signed and personally dated by the participant or by the participant's legally acceptable representative, and by the person who conducted the informed consent discussion.
   • If a participant is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the written informed consent form and any other written information to be provided to participants, is read and explained to the participant or the participant’s legally acceptable representative, and after the participant or the participant’s legally acceptable representative has orally consented to the participant’s participation in the trial and, if capable of doing so, has signed and personally dated the informed consent form, the witness should sign and personally date the consent form. By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the participant or the participant's legally acceptable representative, and that informed consent was freely given by the participant or the participant’s legally acceptable representative.
   • Both the informed consent discussion and the written informed consent form and any other written information to be provided to participants should include explanations of the following:
     • That the trial involves research.
     • The purpose of the trial.
     • The trial treatments and the probability for random assignment to each treatment.
     • The trial procedures to be followed, including all invasive procedures.
     • The participant's responsibilities.
     • Those aspects of the trial are experimental.
     • The reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant.
     • The reasonably expected benefits. When there is no intended clinical benefit to the participant, the participant should be made aware of this.
     • The alternative procedures or courses of treatment that may be available to the participant, and their important potential benefits and risks.
     • The compensation and/or treatment available to the participant in case of trial-related injury.
     • The anticipated prorated payment, if any, to the participant for participating in the trial.
     • The anticipated expenses, if any, to the participant for participating in the trial.
     • That the participant's participation in the trial is voluntary and that the participant may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the participant is otherwise entitled.
     • That the monitors, the auditors, the IRB, and the regulatory authorities will be granted direct access to the participant's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the participant, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the participant or the participant's legally acceptable representative is authorizing such access.
     • That records identifying the participant will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the participant’s identity will remain confidential.
     • That the participant or their legally acceptable representative will be informed promptly if information becomes available relevant to the participant's willingness to continue participation in the trial.
     • The people to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury.
     • The foreseeable circumstances and/or reasons under which the participant's participation in the trial may be terminated.
     • The expected duration of the participant's participation in the trial.
     • The approximate number of participants involved in the trial.
   • Prior to participation in the trial, the participant or the participant's legally acceptable representative should receive a copy of the signed and dated written informed consent form and any other written information provided to the participants. During a participant’s participation in the trial, the participant or the participant’s legally acceptable representative should receive a copy of the signed and dated consent form updates and a copy of any amendments to the written information provided to participants.
   • When a clinical trial (therapeutic or non-therapeutic) includes participants who can only be enrolled in the trial with the consent of the participant’s legally acceptable representative (e.g., minors, or patients with severe dementia), the participant should be informed about the trial to the extent compatible with the participant’s understanding and, if capable, the participant should sign and personally date the written informed consent.
   • Except as described above, a non-therapeutic trial (i.e. a trial in which there is no anticipated direct clinical benefit to the participant), should be conducted in participants who personally give consent and who sign and date the written informed consent form.
   • Non-therapeutic trials may be conducted in participants with the consent of a legally acceptable representative provided the following conditions are fulfilled:
     • The trial's objectives cannot be met by a trial in participants who can give informed consent personally.
     • The foreseeable risks to the participants are low.
     • The negative impact on the participant’s well-being is minimized and low.
     • The trial is not prohibited by law.
     • The approval opinion of the IRB is expressly sought on the inclusion of such participants, and the written approval opinion covers this aspect. Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended. Participants in these trials should be closely monitored and withdrawn if they appear unduly distressed.
   • In emergency situations, when prior consent of the participant is not possible, the consent of the participant's legally acceptable representative, if present, should be requested. When prior consent of the participant is not possible, and the participant’s legally acceptable representative is not available, enrolment of the participant should require measures described in the protocol and/or elsewhere, with documented approval opinion by the IRB, to protect the rights, safety, and well-being of the participant and to ensure compliance with applicable regulatory requirements. The participant or the participant's legally acceptable representative should be informed about the trial as soon as possible and consent to continue and other consent as appropriate should be requested.
   • If the study is a clinical trial and supported by a Common Rule agency, one IRB-approved version of a consent form that has been used to enroll participants must be posted on a public federal website designated for posting such consent forms. The form must be posted after recruitment closes, and no later than 60 days after the last study visit. Contact the study sponsor with any questions.
9. Records and Reports
   • The investigator should ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in the CRFs and all required reports.
   • Data reported on the CRF, that are derived from source documents, should be consistent with the source documents or the discrepancies should be explained.
   • Any change or correction to a CRF should be dated, initialed, and explained (if necessary) and should not obscure the original entry (i.e. an audit trail should be maintained); this applies to both written and electronic changes or corrections. Sponsors should provide guidance to investigators and/or the investigators' designated representatives on making such corrections. Sponsors should have written procedures to assure that changes or corrections in CRFs made by sponsor's designated representatives are documented, are necessary, and are endorsed by the investigator. The investigator should retain records of the changes and corrections.
   • The investigator/institution should maintain the trial documents as specified in Essential Documents for the Conduct of a Clinical Trial and as required by the applicable regulatory requirements. The investigator/institution should take measures to prevent accidental or premature destruction of these documents.
   • Essential documents should be retained until at least 2 years 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 or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period, however, if required by the applicable regulatory requirements or by an agreement with the sponsor. The sponsor is responsible for informing the investigator/institution when these documents no longer need to be retained.
   • The financial aspects of the trial should be documented in an agreement between the sponsor and the investigator/institution.
   • Upon request of the monitor, auditor, IRB, or regulatory authority, the investigator/institution should make available for direct access all requested trial-related records.
10. Progress Reports
    • The investigator should submit written summaries of the trial status to the IRB annually, or more frequently if requested by the IRB.
    • The investigator should promptly provide written reports to the sponsor, the IRB, and, where applicable, the institution on any changes significantly affecting the trial's conduct and/or increasing the risk to participants.
11. Safety Reporting
    • All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate reporting. The immediate reports should be followed promptly by detailed, written reports. The immediate and follow-up reports should identify participants by unique code numbers assigned to the trial participants rather than by the participant's names, personal identification numbers, and/or addresses. The investigator should also comply with the applicable regulatory requirements related to the reporting of unexpected serious adverse drug reactions to the regulatory authorities and the IRB.
    • Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the periods specified by the sponsor in the protocol.
    • For reported deaths, the investigator should supply the sponsor and the IRB with any additional requested information (e.g., autopsy reports and terminal medical reports).
    • Premature Termination or Suspension of a Trial If the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform the trial participants, should assure appropriate therapy and follow-up for the participants, and, where required by the applicable regulatory requirements, should inform the regulatory authorities. In addition:
      • If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution where applicable, and the investigator/institution should promptly inform the sponsor and the IRB and should provide the sponsor and the IRB a detailed written explanation of the termination or suspension.
      • If the sponsor terminates or suspends a trial, the investigator should promptly inform the institution where applicable and the investigator/institution should promptly inform the IRB and provide the IRB a detailed written explanation of the termination or suspension.
      • If the IRB terminates or suspends its approval opinion of a trial, the investigator should inform the institution where applicable and the investigator/institution should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension.
12. Final Reports by Investigator: Upon completion of the trial, the investigator, where applicable, should inform the institution; the investigator/institution should provide the IRB with a summary of the trial’s outcome, and the regulatory authorities with any reports required.

1. IRB Review and Approval: Research protocols involving human participants must receive IRB review and approval before obtaining approval from the Department of Defense (DoD), if this is a requirement of the specific DoD funding component. Researchers should consult with the relevant DoD funding component to determine whether prior IRB approval is necessary.
2. Collaboration for Military Research: Civilian researchers who wish to access military volunteers should collaborate with a military researcher who is familiar with the specific requirements of the services involved. This collaboration ensures compliance with service-specific guidelines and facilitates access to military populations.
3. Compensation for DoD Employees: Employees of the Department of Defense, including those in temporary, part-time, and intermittent positions, may need to check with their supervisors before accepting payment for participation in research. DoD employees are prohibited from receiving payment for conducting research while on active duty.
4. Command Permission: Service members must adhere to their command’s policies regarding participation in research involving human participants, both when on-duty and off-duty. Compliance with these policies is necessary for ensuring proper authorization and adherence to military regulations.
5. Research-Related Injury: The DoD may impose stricter requirements for handling research-related injuries compared to those outlined in DHHS regulations. Researchers should be aware of and comply with these additional requirements to address any injuries or adverse events effectively.
6. Educational Requirements: There may be specific educational or certification requirements for personnel involved in DoD research. These requirements ensure that researchers are adequately trained and qualified to conduct research within the DoD framework.
7. Institutional Evaluation: When assessing whether to support or collaborate with an institution for research involving human participants, the DoD may evaluate the institution’s education and training policies. This evaluation helps ensure that the research personnel are properly qualified to conduct the research.
8. Dual Compensation Limitations: The Department of Defense has specific rules regarding compensation for research activities. Federal employees are prohibited from receiving compensation for research conducted during their duty hours. Non-Federal individuals may receive compensation for research participation, including blood draws, up to $50 per draw. For other types of research participation, non-Federal persons may be compensated a reasonable amount as approved by the IRB, based on local prevailing rates and the nature of the research.
9. Surveys and DoD Review: Surveys conducted on DoD personnel must be submitted to and approved by the DoD Information Management Control Officer (IMCO) following IRB approval. If a survey involves multiple DoD components, additional review is required to ensure compliance with DoD policies.
10. Large Scale Genomic Data (LSGD) Protections: Research involving large-scale genomic data collected from DoD-affiliated personnel requires additional safeguards. These include administrative, technical, and physical measures to prevent unauthorized disclosure of data. The research must also apply for an HHS Certificate of Confidentiality and undergo a DoD Component security review.
11. Confidentiality of Data: Data or information sent to a DoD component under a pledge of confidentiality for statistical purposes must be used exclusively for those purposes. Such data may not be disclosed in identifiable form for any other purpose without the informed consent of the respondent.
12. Multi-Site Research Agreements: For multi-site research, a formal agreement between institutions is required. This agreement should clearly define the roles and responsibilities of each party involved in the research to ensure coordination and compliance with research protocols.
13. Reporting to DoD: Researchers must report several types of information to the applicable DoD Component Office of Human Research Protections within 30 days. This includes significant changes to the research protocol that have been approved by the IRB or Ethics Committee, such as changes to key investigators or institutions, decreases in benefit or increases in risk to participants in greater than minimal risk research, the addition of vulnerable populations or DoD-affiliated personnel as participants, and changes in the reviewing IRB. Notifications must also be made if the organization is informed by any federal body, state agency, governing body of Native American or Alaskan Native tribes, or other entities about an investigation involving DoD-supported research protocols. Additionally, researchers should report any problems involving risks to participants or others, suspension or termination of IRB approval, or serious or continuing noncompliance related to DoD-supported research. Results of the IRB’s continuing review, if required, should be submitted, along with any changes in status for previously enrolled participants, such as pregnancy or imprisonment, if these changes were not reviewed and approved by the IRB in accordance with applicable regulations. Finally, closure of a DoD-supported study must be reported.
14. Approval for Sensitive Research: For research that may affect the health or welfare of pregnant women, fetuses, or neonates, written approval from the DoD Office for Human Research Protections is required before starting the research. This ensures that such sensitive research is conducted with appropriate oversight and ethical considerations.

1. IRB Review and Approval: Research that involves studying humans in a systematically modified environment, including intentional modifications such as using tracer chemicals to characterize airflow or testing new materials in occupied homes or offices, must be submitted to the appropriate IRB for review and determination. This includes studies involving social media data, Human Terrain Mapping (HTM), and all exempt human subjects research (HSR) determinations.
2. Protection of Personally Identifiable Information: Personally identifiable information (PII) collected during HSR projects must be protected in accordance with DOE Order 206.1, the Department of Energy Privacy Program. Researchers must submit protocols that include PII to the Central DOE IRBs.
3. Reporting: Prior to initiating any new human subjects research project, researchers must report to the DOE human subjects research Program Manager (and, if applicable, the NNSA HSP Program Manager) if the research involves an institution without an established IRB, a foreign country, potential for significant controversy, protected classes of research subjects, or the generation or use of classified information. This includes projects that meet the regulatory definition of exempt research under 10 CFR Part 745.104.
4. Notifications: The IRB and the DOE HSP Program Manager (and NNSA HSP Program Manager, if applicable) must be notified within 48 hours of any adverse events, unanticipated problems, complaints, suspensions or terminations of IRB approval, significant noncompliance, suspected or confirmed data breaches involving PII, and serious adverse events and corrective actions. "Immediately" is defined as upon discovery.
5. Classified Research: Human participant protections for classified research apply to all classified research conducted or supported by the DOE and its national laboratories, including contracts and Human Terrain Mapping research.
6. International Research Requirements: Researchers conducting human subjects research in foreign countries must adhere to the country-specific human subjects research requirements and consult with the IRB about the applicability of these requirements.
7. FWA and IRB Approval: Human subjects research conducted with DOE funding, at DOE institutions, or by DOE or contractor personnel, whether domestic or international, requires both Federalwide Assurance (FWA) or comparable assurance and approval by the cognizant IRB. Research involving multiple DOE sites must be reviewed and approved by a Central DOE IRB or another appropriate IRB as authorized by the DOE or NNSA HSP Program Manager. An IRB Authorization Agreement (IAA) or Memorandum of Understanding (MOU) is required between the organizations conducting the research and the IRB.
8. DOE Employee Research: Research involving DOE Federal and/or contractor employees must be reviewed and approved by the appropriate DOE IRB or another suitable IRB, in accordance with an IAA or MOU negotiated between the DOE site or Headquarters and the IRB.
9. Strategic Intelligence Partnership Program (SIPP): Classified and unclassified human subjects research funded through the SIPP must be reviewed and approved by the Central DOE IRB-Classified.
10. Paperwork Reduction Act: Federally funded HSR must comply with the Paperwork Reduction Act, if applicable.

1. Exclusions and Compatibility: Implementation of Bureau programmatic or operational initiatives through pilot projects is not considered research. The research must avoid medical experimentation, cosmetic research, or pharmaceutical testing and must be compatible with the operation of prison facilities and the protection of human participants.
2. Institutional Rules and Agreements: Investigators must adhere to the rules of the institution or office where the research is conducted. Non-employees of the Bureau of Prisons must sign a statement agreeing to comply with the requirements of 28 CFR §512.
3. Review and Approval: The research must be reviewed and approved by the Bureau Research Review Board. Incentives cannot be offered to persuade inmate participants, though soft drinks and snacks may be provided at the test setting. Nominal monetary recompense for time and effort may be offered to non-confined participants involved in authorized research conducted by Bureau employees or contractors.
4. Use and Disclosure of Records: Non-employees of the Bureau may receive records in a non-individually identifiable form if advance written assurance is provided that the records will be used solely for statistical research or reporting. Research information identifying participants cannot be released without the participant’s prior written consent. Research records containing non-disclosable information directly traceable to a specific person may not be stored in or introduced into an electronic retrieval system, except for computerized data records maintained at an official DOJ site.
5. Data Handling for Special Interest Studies: If conducting a study of special interest to the Office of Research and Evaluation that is not a joint project, researchers may be required to provide non-identifiable computerized research data and detailed documentation. These arrangements must be negotiated before data collection begins.
6. Required Elements of Disclosure: Required disclosures must include several key components. The identification of the investigators and the anticipated uses of the research results must be clearly stated. Participants should be informed that their involvement is voluntary, with the option to withdraw at any time without facing any penalty or prejudice. The confidentiality of research information must be addressed, noting any exceptions to confidentiality guarantees required by federal or state law. Participants should be assured that their participation will not influence their release date or parole eligibility.
7. Academic Preparation: Researchers must have appropriate academic preparation or experience related to the proposed study.
8. IRB Application Requirements: The IRB application must contain a comprehensive summary of the study, including the names and current affiliations of the investigators, the title and purpose of the study, the location where the research will be conducted, the methods to be used, and the anticipated results. It should also outline the duration of the study, the number of participants required, the amount of time needed from each participant, and any risks or discomforts involved. In addition, the application must include a detailed description of the research method, a review of related literature, the significance of the results, the resources required from the Bureau of Prisons, and a discussion of the risks, benefits, and steps taken to minimize risks. It should describe physical or administrative procedures to ensure data security and the destruction of records when the research is complete, as well as any anticipated effects of the study on institutional programs and operations. Relevant research materials such as vitae, endorsements, consent statements, questionnaires, and interview schedules must also be included.
9. Assurances and Certification: The IRB application must include a statement regarding assurances and certifications required by federal regulations, if applicable.
10. Responsibility and Reporting: Researchers are responsible for the actions of associates, assistants, or subcontractors. At least once a year, researchers must provide the Chief, Office of Research and Evaluation, with a progress report. At least 12 working days before releasing findings, researchers must distribute a copy of the report to the Bureau Research Review Board chairperson, regional director, and warden of each institution that provided data or assistance. An abstract must be included in the report.
11. Publication and Disclosure: In any publication of results, the Bureau's participation must be acknowledged, but the publication should explicitly disclaim approval or endorsement of the material as reflecting the Bureau's policies or views. Prior to publication, researchers must provide two copies of the material to the Chief, Office of Research and Evaluation, Central Office, Bureau of Prisons for informational purposes only.

1. Privacy Certificate: The project must have a Privacy Certificate approved by the National Institute of Justice (NIJ) Human Participants Protection Officer. This ensures compliance with confidentiality and data protection standards.
2. Confidentiality Statements: All investigators and research staff are required to sign employee confidentiality statements, which are maintained by the responsible investigator. These statements affirm their commitment to safeguarding participant information. The confidentiality statement in the consent document must specify that confidentiality can only be breached if there is an immediate risk of harm to participants or others. This ensures participants are aware of the limits to confidentiality. Under the Privacy Certificate, investigators and research staff are not required to report child abuse unless the participant has signed an additional consent document permitting such reporting. This provision aligns with specific confidentiality agreements.
3. Data Management: A copy of all data must be de-identified and submitted to the National Archive of Criminal Justice Data, including copies of the informed consent document, data collection instruments, surveys, and other relevant research materials. This practice ensures that sensitive information is handled appropriately and maintains participant anonymity.

1. Compliance Assurance: Each school where research is conducted must provide assurance that it complies with the Family Educational Rights and Privacy Act (FERPA) and the Protection of Pupil Rights Amendment (PPRA). This ensures adherence to federal privacy and rights standards.
2. Materials Inspection: Researchers must provide copies of all surveys and instructional materials used in the research. Upon request, parents of children involved in the research must be able to inspect these materials, ensuring transparency and parental oversight.
3. School Policies: The school where the research is being conducted must have established policies regarding the administration of physical examinations or screenings that may be administered to students. This ensures that all procedures align with institutional and regulatory standards.

1. EPA Regulations: Research conducted, supported, or intended for submission to the EPA is subject to Environmental Protection Agency Regulations. Compliance with these regulations is mandatory to ensure environmental safety and protection.
2. Prohibition on Exposure: Intentional exposure of pregnant women or children to any substance is strictly prohibited. This measure protects vulnerable populations from potential harm.
3. Additional DHHS Requirements: Observational research involving pregnant women and fetuses must comply with additional Department of Health and Human Services (DHHS) requirements for research involving pregnant women (45 CFR §46 Subpart B) and children (45 CFR §46 Subpart D). This includes adherence to stricter ethical guidelines.
4. Research Categories: Research involving children must meet the criteria specified in category #1 or #2, ensuring appropriate ethical standards are applied.