7. Clinical Trial-Related Activities (including Remote Monitoring)
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7. Clinical Trial-Related Activities (including Remote Monitoring)
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Clinical Trials Ontario, a not-for-profit organization, has collated a resource guide for the conduct of DCTs, which is a useful indicator of DCT processes throughout Canada due to the currently “opaque” requirements of Health Canada and the REBs. This resource will be referred to as the “Unofficial DCT Resource Guide” throughout this guidebook.
Notes:
- If no interaction is needed, the investigator can consider virtual visits (telehealth) instead of in-person visits. The protocol should specify when this could be appropriate.
- It is very important that, during each remote visit, the investigator confirms the identity of the participant.
- The province of Saskatchewan implemented virtual care in 1999. Details of its remote monitoring methods are available on the Canada Health website.
The following sub-sections should be considered for clinical trial-related activities along with remote monitoring.
7.1 Protocol Development
The clinical investigational protocol shall be based on the evaluation of pre-clinical data and the result of clinical evaluation and shall be aligned with the results of the risk assessment: clinical performance, effectiveness, or safety of the investigational product or similar IP or therapies and should be relevant to the intended purpose and the proposed method of use. The study protocol shall clearly outline the objectives of the clinical investigation and the proposed design shall be adequately justified based on scientific and ethical principles. The protocol or any amendment shall include the following topics:
- Trial Title and Number
- Background / Rationale
- Trial Objectives
- Study Design
- Study Duration
- Number of Sites (inside and outside of Canada)
- List of Investigators
- Sample Size
- Patient Population
- Inclusion Criteria
- Exclusion Criteria
- NHP Formulation
- Dosage Regimen
- Pre-study Screening and Baseline Evaluation
- Treatment Visit
- Premature Withdrawal/Discontinuation Criteria
- Rescue Medication (if applicable)
- Washout Period (if applicable)
- Concomitant Medication
- Variables to be Assessed
- Efficacy Analysis
- Safety Analysis
- Statistical Analysis
- Current Problems/Concerns
7.2 eConsent/Remote Consent
eConsent is permitted in Canada if all applicable regulatory/ICH-GCP requirements are met, including that the system must be properly validated with documented procedures and appropriate training, all required elements must be present in the ICF, and the information must be stored for 15 years. (The clinical trial records retention period for drugs has been changed from 25 years to 15 years as per section C.05.012 (4) of the Food and Drug Regulations, as of February 11, 2022.)
Remote consent is permitted if the communication platforms and consent approach to be used have received prior approval from REBs, privacy, and IT departments.
Health Canada regulations note that the process for obtaining informed consent via electronic means should also be detailed in an SOP, including how the form will be explained and discussed with the clinical trial participant (e.g. will the participant have the option to sign a paper copy, bring a copy home or have access to an electronic signed copy, etc.).
7.3 eSignature, including any requirement for a countersignature (e.g., of PI, witness, etc.)
eSignature is permitted if the considerations for eConsent and Remote Consent, as applicable, mentioned in section 7.2 above, have been met.
Subsection C.05.012(4) of the Food and Drug Regulations requires a participant to have the option to access an electronically signed copy of an eConsent form, which itself is required to be obtained in compliance with the requirements for obtaining informed consent, though via electronic means. It may be assumed that eSignature may include any requirement for countersignature as required by the procedure for obtaining informed consent as followed in clinical trials.
7.4 Remote Assessment
From the research conducted, no specific guidance could be located which specifically regulates remote assessment as a feature of DCTs. It is submitted that the guidelines contained in the “Unofficial DCT Resource Guide” for PI Oversight be extended to aspects of a trial for which the PI is responsible, though they may occur in a digital or remote manner.
7.5 Electronic Patient Reported Outcome (ePro)
From the research conducted, no specific guidance could be located which specifically regulates remote assessment as a feature of DCTs. It is submitted that the guidelines contained in the “Unofficial DCT Resource Guide” for PI Oversight might be extended to aspects of a trial for which the PI is responsible, though they may occur in a digital or remote manner.
7.6 HHC – Home Nursing
A third-party vendor may be engaged to perform in-home services for DCT trials, provided that Health Canada and relevant REBs have provided guidance in order to define investigator responsibilities regarding participant care oversight and the potential delegation of activities.
7.7 HHC – Home Lab Collection
Please refer to section 7.6 above.
7.8 Monitoring and Remote Monitoring
As the sponsor may use a variety of approaches to monitor the trial, it is important to make sure that the clinical trial protocol describes the operational aspects of the trial and how it will be implemented. The risk assessment needs to be described in the monitoring plan and describes how monitoring will be implemented to assess data quality and integrity and protocol compliance. The monitoring plan should also specify for reviewing the trial records and source documents with any unique aspect related to the DCT procedures.
Monitoring and remote monitoring visits may occur and are subject to Health Canada and REB conditions. This means that the Informed Consent Form (ICF) should inform the participant that their medical records and study information may be reviewed remotely by the sponsor while maintaining the patient’s privacy and confidentiality, and the REB may want the ICF to be explicit on the mediums for record access. In the absence of regulations or guidance from Health Canada, the guidelines advise that the principles of ICH-GCP be deferred to.
7.9 Telemedicine
From the research conducted, no specific guidance could be located which specifically regulates telemedicine as a feature of DCTs. It is submitted that the guidelines contained in the “Unofficial DCT Resource Guide” for PI Oversight, discussed in section 7.4 above, be extended to aspects of a trial for which the PI is responsible, though they may occur in a digital or remote manner.
7.10 Wearables
From the research conducted, no specific guidance could be located which specifically regulates wearables as a feature of DCTs. It is submitted that the guidelines contained in the “Unofficial DCT Resource Guide” for Remote Data Monitoring, discussed in section 7.8 above, be extended to aspects of a trial in which data is gathered, though this may occur in a digital or remote manner.
7.11 Sponsor and Qualified Investigator Roles and Responsibilities
As per the definitions, the Qualified Investigator is the person:
- Responsible to the sponsor for the conduct of the clinical trial at the clinical trial site,
- Who is entitled to provide health care under the laws of the province where that clinical trial site is located, and
- Who is, in the case of a clinical trial respecting a drug to be used for dental purposes only, a physician or dentist and a member in good standing of a professional medical or dental association. https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.pdf
The Sponsor is an individual, corporate body, institution, or organization that conducts a clinical trial as per Division 5. The sponsor must comply with its obligations as set out in the Regulations (including C.05.010-C.05.015) in adhering to good clinical practices for the proper use of the drugs, drug labeling requirements, record keeping, submission of information, reporting of ADRs, and trial discontinuation reporting requirements.
7.12 Essential Document Collection
The sponsor and the qualified investigator/investigation site should maintain a record of the location of their respective essential documents. The storage system should provide for document identification, version history, search, and retrieval whether it was paper-based or electronic-based storage.
ICH-GCP guidance defines essential documents as “those documents which individually and collectively permit evaluation of the conduct of the clinical trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor, and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements”.
A Trial Master File (TMF) should be established at the beginning of any research study and maintained throughout the study until its completion. Below is the required documents to be collected and maintained as per ICH-GCP regardless of the type of clinical trial:
- Investigator's Brochure (IB)
- FDA Form 1572 (or 81(k))
- Delegation of Responsibilities Log
- Protocol and Amendments
- Information Given to a Study Participant
- Informed Consent
- Other Written Information
- Recruitment Advertisement
- Financial Disclosure Form (FDF)
- Master Clinical Trial Agreement (MCTA)
- IRB Approval
- IRB Roster
- IRB Correspondence
- Curriculum Vitae (CV)
- Medical Licensure
- Training Records
- Laboratory Certification or Accreditation
- Laboratory Normal Values
- Monitor Visit Reports
- Sponsor Correspondence
- Miscellaneous Documentation
- Source Documents
- Notification of Serious Adverse Events by Investigator to Sponsor
- Notification of Serious Adverse Events by Sponsor to Regulatory Authorities
- Subject Screening Log
- Subject Identification Log
- Subject Enrollment Log
- Signature Sheet
- Investigational Product Accountability Log
- Documentation of Investigational Drug Destruction
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