Table 2.
TransCelerate criteria: results of survey and group discussion regarding behavioral trial differences
| TransCelerate criteria | n | Report of “yes it applies” [% (n)] | Comments from group on how behavioral trials are different | |
|---|---|---|---|---|
| 1 | Investigator qualifications and agreements | |||
| Investigator qualification (education, training, experience) Demonstrate evidence of adequate training (provide up-to-date CV) Awareness of and compliance with GCP and regulatory requirements IP familiarity Allow for monitoring/auditing/inspection to enable sponsor/regulatory oversight Introduce definitions of monitoring (1.38), audit (1.6), and inspection (1.29) Use of qualified support staff Document delegation of duties to appropriately qualified persons | 15 | 93 (14) 93 (14) 67 (10) 7 (1) 40 (6) 47 (7) 100 (15) 87 (13) | No IP No requirement to comply to GCP Different methods of monitoring, audit, and inspection (may be different within behavioral trials depending on risk level of trial) Sponsor/regulatory oversight is different | |
| 2 | Adequate resources | |||
| Potential to recruit suitable subjects Sufficient time to conduct trial Sufficient qualified staff and adequate facilities to conduct trial Staff are adequately informed about protocol, IP, and tasks related to the protocol | 15 | 93 (14) 93 (14) 93 (14) 80 (12) | ||
| 3 | Medical care of trial subjects | |||
| Qualified physician or dentist who is an investigator or sub-investigator should be responsible for all trial-related medical decisions During and following the trial, the investigator/institution should ensure appropriate medical care for AEs and clinically significant lab deviations related to trial and inform subjects if medical care is needed for intercurrent illness Physician to make a reasonable effort to ascertain the reasons for subject’s premature withdrawal from the trial | 15 | 27 (4) 40 (6) 33 (5) | Trial dependent May not need a qualified physician, dentist, etc. for trial-related medical decisions Ensuring appropriate care for AEs or lab deviations Ascertain reasons for a subject’s premature withdrawal from a trial Good for tracking purposes in behavioral trial, but maybe not for “medical care” reasons | |
| 4 | Communication with IRB/IEC | |||
| Definition of IRB (1.31) and IEC (1.27) Before trial begins, obtain written, dated approval/favorable opinion for protocol and all documents provided to subjects (eg, ICF, advertisements) Provide a copy of investigator’s brochure/updated IB Before and during the trial, provide all documents required by IRB/IEC for review and appropriate approval/favorable opinion | 15 | 93 (14) 80 (12) 7 (1) 80 (12) | No investigational brochure required May be different level of communication depending on risk level of behavioral trial | |
| 5 | Compliance with protocol | |||
| Conduct trial according to approved protocol, GCP, and applicable regulatory requirements, for example, sufficient documentation to support subject meeting inclusion/exclusion criteria Document the acceptance to follow protocol in a protocol signature page or contract Protocol deviation process—no deviations or changes before sponsor and IRB/IEC approval/favorable opinion | 15 | 93 (14) 60 (9) 60 (9) | Do not conduct trial according to regular GCP Documenting acceptance to follow protocol in a protocol signature page (trial specific, depends on study sponsor) Protocol deviation may not need same level of reporting (ie, documented and rationale submitted to sponsor) | |
| 6 | IPs | |||
| Responsibility for IP (refer to 1.33) accountability and delegation of activities and supervision of an appropriately qualified person Documentation of delivery, inventory, dispensation, usage, disposal or return, and reconciliation of all IP and other study medication Stored per requirement Explanation of correct use of IP to subjects and periodic check for understanding/compliance | 15 | 33 (5) 20 (3) 20 (3) 20 (3) | Not applicable | |
| 7 | Randomization procedures and unblinding | |||
| Follow the trial’s randomization procedures Blinded trials: promptly document and report to sponsor any premature unblinding | 16 | 88 (14) 38 (6) | May not need to unblind in a behavioral trial | |
| 8 | Informed consent of trial subjects | |||
| Definition of informed consent (1.28) Explain the informed consent process and ICF IRB/IEC written approval in advance of use for written consent and other written information to be provided to subjects Subject to be fully informed of all pertinent aspects of the trial before participation The informed consent discussion and form needs to include all relevant explanations. Refer or link to ICH 4.8.10 Language used in oral and written information (ICF) should be understandable to subject or legal representative and impartial witness (where applicable) Subject should have ample time to review the ICF and to ask any questions and receive answers before decision is made Subject should not be unduly influenced to participate ICF should be obtained/signed before a subject’s participation in a trial (before any study procedures are performed) Subject should be aware that withdrawal is possible at any time Subject should not be asked to waive legal rights or release investigator or sponsor from liability for negligence Written ICF must be updated/approved when new information is available that may be relevant to subject’s consent | 16 | 82 (13) 94 (15) 94 (15) 94 (15) 94 (15) 94 (15) 94 (15) 94 (15) 94 (15) 94 (15) 88 (14) | Informed consent process not often feasible to be documented in medical record as these trials may occur outside a clinical setting | |
| Informed consent of special population Refer to or add definition of vulnerable subjects (1.61) When a subject (eg, minor, incapacitated) can only be enrolled with the consent of the legal representative, the subject must be informed to the level of their understanding, provide assent (where this is feasible), and personally sign and date the consent form In emergency situations, where the subject and legal representative are unable to consent, enrollment requires protective measures to be described in protocol or other IRB/IEC-approved documents. Subject or legal representative should be informed as soon as possible and consent to continue and other consent as appropriate If the subject/legal representative are unable to read, an impartial witness must be present during the consent discussion and sign and date the consent form Informed consent documentation The ICF should be signed and personally dated by the subject and/or the legal representative and by the person who conducted the consent A signed and dated copy of the ICF should be given to the subject or the legal representative (including any other written information provided to the subject) The informed consent process should be documented in the medical record/source file (as well as documentation regarding communication of new information) | 16 | 88 (14) 94 (15) 75 (12) 94 (15) 82 (13) 82 (13) 50 (8) | ||
| 9 | Records and reports | |||
| Definition of source documents: the actual documents (originals), GCP glossary 1.52 (brief) Refer to or add definition of source data (1.51) Definition of essential documents (section 8) The need to maintain essential documents. Refer/link to section 8 Retention of essential documents CRFs and all required reports (written or electronic) Corrections are dated and initialed, do not obscure original entry and explained if necessary (applies to written and electronic changes/updates). Retain records of changes and corrections Financial aspects documented in an agreement between sponsor and investigator/institution Direct access to all trial-related documents by the monitor, the auditor, the IRB/IEC, or regulatory authority | 16 | 69 (11) 56 (9) 69 (11) 75 (12) 81 (13) 75 (12) 75 (12) 75 (12) 75 (12) | Source documents and essential documents may have specific meaning for drug trials not applicable/known to behavioral trials Financial aspects in sponsor agreement appears to refer to drug trials only | |
| 10/13 | Progress reporting/final reports | |||
| Investigator submits written summaries of progress to IRB/IEC at least annually or as required Provide written reports to sponsor and IRB/IEC (and institution where required) of any significant changes affecting the study or increased risk to subjects Upon completion of trial, provide sponsor with all required reports Final report with a summary of trials and outcomes submitted to IRB/IEC and regulatory authorities as required | 16 | 88 (14) 81 (13) 81 (13) 75 (12) | Final report submitted to IRB/regulatory authorities may be trial specific | |
| 11 | Safety reporting | |||
| AE definition (1.2) Refer to or add definition of ADR (1.1) and unexpected ADR (1.60) AE reporting—all AEs and/or laboratory abnormalities should be reported to the sponsor within the time period defined in protocol All SAEs should be reported immediately to the sponsor except for those SAEs that the protocol or other document (eg, investigator’s brochure) identifies as not needing immediate reporting | 6 (1) 56 (9) 56 (9) | ADR is not applicable Reporting of SAEs is likely to be on different timeline than in drug trials | ||
| 12 | Premature termination or suspension of trial | |||
| Responsibility to promptly inform the trial subjects and ensure appropriate therapy and follow-up. Inform regulatory authorities when required Responsibility for communication of study termination or suspension of study to sponsor, IRB/IEC, and institution as applicable, including a detailed written explanation | 16 | 63 (10) 75 (12) | May be trial specific |
GCP, Good Clinical Practice; IP, investigational product; AE, adverse event; ICF, informed consent form; SAE, serious adverse event; ADR, adverse drug reaction.