Conducting clinical trials in canada

Annual Report. Revisions that are more frequent may be appropriate depending on the stage of development and the generation of relevant new information. In all cases, the updated IB should be accompanied by a list of changes that clearly describe the sections that have changed, including a rationale for each change. Final Report. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement.

The CRO should implement quality assurance and quality control. A foreign sponsor is required to have a senior medical or scientific officer who is residing in Canada who will represent the sponsor, and sign and date the application and the clinical trial attestation form. The CTA package includes, but is not limited to:.

See the Clinical Trial Lifecycle topic, Submission Content subtopic for detailed submission requirements. HC will issue an NSN if it identifies significant deficiencies, or, if a timely response to information requested has not been provided. The CanadaFDR does not require the sponsor to provide insurance coverage to investigators, institutions, or trial participants. The Canadian regulations do not require compensation for trial participants in the event of trial-related injuries or death.

However, the CA-ICH-GCPs provides guidance for sponsors on providing compensation to research participants in the event of trial-related injuries or death. See Informed Consent topic, Compensation Disclosure subtopic for more information on participant compensation rights. Per the CA-ICH-GCPs , the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results.

QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. A written agreement must be signed by both the sponsor and the investigator or any other parties involved with the clinical trial, verifying that both parties agree to the trial protocol, the monitoring and auditing practices, the SOPs, and their respective duties.

In addition, the sponsor must maintain SOPs that cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. With respect to the use of these computerized systems, the responsibilities of the sponsor, investigator, and other parties should be clear, and the users should receive relevant training.

This evidence of validation should be kept for the required record retention period and available for inspection by HC inspectors. See the G-FDR for additional details.

As set forth in the CanadaFDR and the CanadaFDR , the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification.

The sponsor should maintain all trial-related records for a period of 25 years. Additionally, to facilitate inspection of a site, the sponsor must submit information to HC within seven 7 days of a request. Per CAN-8 , an attestation must be completed by the ethics committee that reviewed and approved the clinical trial. The storage system used during the trial and for archiving irrespective of the type of media used should allow for document identification, version history, search, and retrieval.

The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The sponsor should appoint auditors to review the clinical trial. The sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency.

The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy e.

The CanadaFDR states that if a trial is prematurely terminated or suspended, the sponsor should inform HC no later than 15 days after the termination or suspension.

In addition, the sponsor should provide HC with the reason s for the termination or suspension and its impact on the proposed or ongoing clinical trials related to the drug in Canada by the sponsor. According to the CA-ICH-GCPs , if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions.

Further, the ethics committee EC should also be informed promptly and provided the reason s for the termination or suspension by the sponsor. The G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ECs, provides that in multi-site clinical trials, a lead principal investigator lead PI is a designated PI who is responsible for the ethical conduct of the study for all sites.

Per HCNotice-ICH-E17 , HC announced the implementation of CAN , which describes general principles for the planning and design of multi-regional clinical trials with the aim of increasing the acceptability of these trials in global regulatory submissions. HC recognizes that the scope and subject matter of current HC guidance may not be entirely consistent with ICH guidance.

As set forth in the CA-ICH-GCPs , the sponsor should select the investigator s and the institution s for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must also ensure that the investigator s are qualified by training and experience.

If a multicenter trial will be conducted, the sponsor must organize a coordinating committee or select coordinating investigators. Furthermore, the sponsor must sign an agreement or contract with the participating institution s. Per the CanadaFDR , the form certifies that the qualified investigator will conduct the clinical trial in accordance with good clinical practices, and will immediately inform trial participants and the institutional ethics committee EC of trial discontinuance, and the reason for this discontinuance.

See the Clinical Trial Lifecycle topic, Submission Content subtopic for additional information on clinical trial application requirements. Sponsors can use CCTAM to identify potential sites and investigators, which may expedite study feasibility and start-up timelines.

Although not specified as a sponsor requirement, the CA-ICH-GCPs states that a Data and Safety Monitoring Board DSMB known as an Independent Data-Monitoring Committee in Canada may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. A foreign sponsor is required to have a senior medical or scientific officer who is residing in Canada represent the sponsor, and sign and date the application and the clinical trial attestation form.

See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form. CAN notes that the person obtaining consent may also need to explain the consent form verbally to ensure that the participant fully understands the information. See CAN for informed consent and assent templates and sample forms. The communication of this information should be documented. Researchers have an ongoing duty to provide participants with all information relevant to their ongoing consent to participate in the research.

Further, within the limits of consent provided by the participant, researchers should disclose to the participant any material incidental findings discovered in the course of research. Incidental findings are considered to be material incidental findings if they are reasonably determined to have significant welfare implications for the participant or prospective participant.

Where material incidental findings are foreseeable, researchers should inform participants during the initial consent process. In addition, researchers should develop a management plan for review by the EC.

Language Requirements. CAN further specifies that consent forms should be provided in the language that participants are most comfortable with. If there is a language barrier, the G-TCPS2 indicates that the qualified investigator should select an intermediary who has the necessary language skills to ensure effective communication.

Documentation Copies. The witness should sign and date the ICF after the following steps have occurred:. Per CAN , if blood is taken, indicate total volume for example, teaspoons and ml equivalent and note the possibility of bruising or swelling while giving blood, or other possible discomforts at the site where blood is drawn.

Further, state that there may be minimal chance of infection and that discomforts experienced will be brief and transient. CAN also indicates that participants should not be told if an EC has approved the study, since this may appear to offer a guarantee of safety.

Further, no clause or language should be used to excuse or appear to excuse investigators or other persons or institutions involved from liability for their negligence or other faults. Sample consent forms are available from the REB Secretariat upon request: hc.

See the Informed Consent topic, Compensation Disclosure and Vulnerable Populations subtopics and the Specimens topic, Consent for Specimen subtopic for further information.

Compensation for Participation in Research. Any compensation or incentive to participants must not be so excessive that it may unfairly influence participants, or cause them to overlook important facts and risks. Compensation for Injury. The informed consent template in CAN provides that if a participant has any questions about their rights, they should contact:.

The Right to Participate, Abstain, or Withdraw. The Right to Information. The Right to Privacy and Confidentiality. The Right to Safety and Welfare. See the Informed Consent topic , and the subtopics of Required Elements and Vulnerable Populations for additional information regarding requirements for participant rights. Special circumstances may include medical emergencies or a mentally incapacitated participant.

Medical Emergencies. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee EC known as Research Ethics Board in Canada must approve the protocol in advance.

Alteration of Consent. The G-TCPS2 specifies that although voluntary informed consent is always a requirement for every trial, the EC may approve an alteration of consent if the study satisfies all of the following conditions:. If such an event is expected, then procedures to address this circumstance should be clearly explained in the ICF.

As per the G-TCPS2 , in all Canadian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The CA-ICH-GCPs characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from not participating.

Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention.

Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Per CAN , because the G-TCPS2 does not specify an age of consent for children, the decision on whether to seek consent from children is based on whether they have the capacity to understand the research and the risks and benefits of their participation.

Youth who have not reached the age of majority either 18 or 19 depending on the province or territory may still be old enough to provide their own consent. The decision of a child not to assent must be respected regardless of whether third-party consent was obtained. CAN provides the following criteria for determining whether participants can provide their own consent, or whether an authorized third party should be involved:.

CAN states that is generally accepted that youth can consent to minimal risk studies at 16 years of age, and that assent should be sought from children beginning at approximately seven 7 years of age. However, it is ultimately up to the researcher to determine whether to obtain assent or consent from children, and to provide the rationale for this decision to the ethics committee EC known as a Research Ethics Board in Canada.

Researchers should also consider that within a single research project, some minors may be capable of consenting while others may not. See CAN for additional details regarding obtaining consent from minors. As stated in G-TCPS2 , children should only participate in clinical studies when the research objective cannot be achieved with adult participants only. Per G-TCPS2 and TCPS2-InterpCnsnt , where a child has some ability to understand the significance of the research, the researcher must ascertain the wishes of that individual with respect to participation.

Children—whose decision-making capacity is in the process of development—may be capable of verbally or physically assenting to, or dissenting from, participation in research. Further, according to CAN , which offers best practices and guidance to researchers and ECs in pediatric research and complements the G-TCPS2 , provincial laws in Canada vary as to when a child is presumed to be legally competent to provide informed consent.

Some provinces use age while others use a competence-based evaluation. When the child develops the legal capacity to provide informed consent or attains the legal age of majority which depends on the province , researchers should obtain an informed consent.

Regarding dissent, CAN states that the researchers must respect the dissent of a child who is capable of understanding. CAN provides sample assent forms and templates. For more detail and guidance about best practices for research involving pediatric participants, CAN As per the G-TCPS2 , studies involving women of childbearing age, or who are pregnant, require additional safeguards to ensure that the research assesses the risks to the women and the fetuses.

In accordance with the CA-ICH-GCPs , informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Informed Consent topic, Required Elements subtopic.

Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant. A research study involving prisoners should ensure that these prospective participants are informed, and are given the opportunity to make their own decisions without any interference from a higher authority. Per CAN , a dults with diminished decision-making capacity include:.

As is the case for any vulnerable population, care must be taken to ensure that adults with diminished decision-making capacity are not inappropriately included in research because of their situation, and neither should they be excluded from participating in research that may benefit them. In general, many of the same principles for obtaining consent for children apply to adults with diminished decision-making capacity. In such cases, participants should still be involved to the greatest extent possible in the decision-making process, and their assent to participate must be obtained if they are capable of expressing their wishes in a meaningful way whether verbally or physically.

As delineated in the CanadaFDR , the G-GMP-Annex13 , and the CA-ICH-GCPs , an investigational product is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled formulated or packaged in a way different from the approved form. Per the G-CanadaCTApps , sponsors must file amendments or notifications to a previously authorized CTA when manufacturing changes are proposed that may affect the quality or safety of the clinical trial drug or biologic supplies.

HC also authorizes the import of IPs. A sponsor who is not based in Canada must have a representative in Canada who is responsible for the import of the IP and demonstrate compliance to the applicable regulatory requirements. As additional importers are identified, additional copies of Appendix 1 should be provided to HC. A copy of this authorization must be provided at the port of entry. Note that a sponsor does not have to submit a clinical trial application for authorization to import an IP used in a Phase IV clinical trial.

Per the G-FDR , if a sponsor plans to send the clinical trial IP s directly to each trial site, then the sponsor must also meet the following conditions:.

The sponsor must ensure that an up-to-date IB is made available to the investigator s , and the investigator s must provide an up-to-date IB to the ethics committee. The sponsor is also accountable for supplying the IP, which includes ensuring that the IP is supplied by another designated or contracted party, including the comparator s and placebo, if applicable.

The CanadaFDR requires that IPs be packaged and labelled under the supervision of personnel who have had satisfactory technical, academic, and other training. With regard to the expiration date, the G-GMP-Annex13 further states that if it becomes necessary to change the expiration date, an additional label should be affixed to the IP. Our mandate is to provide a streamlined approach to conducting multi-centre clinical trials in Ontario, while maintaining the highest ethical standards for participant protection.

Canada is quickly becoming a destination of choice in terms of running Clinical Trials and more conferences and events are being produced across the country in order to meet the growth of this industry.

Canada Talks Pharma has quickly become a must attend conference in the industry. The most current regulations under Division 5 were implemented to strengthen protections for human research subjects and increase research and development investment in clinical trials in Canada. Once preclinical testing is completed, clinical trial sponsors may move on to Phase 1. Researchers in Phase I aim to find the safe dosage range of a new drug with the fewest side effects.

At the end of this phase, the results are collected and analyzed before being submitted to the appropriate regulatory agency. If approved, the sponsor can proceed with Phase 2, which is carried out to test drug efficacy and monitor any side effects. As a CRO with a large database that can perform high-volume studies and has sites in both the U. This gives clients as much information as possible so that they can make the right decisions. By offering a global network, CROs like BioPharma are familiar with drug markets around the world and able to conduct more complex studies.

They have the expertise and equipment to bring challenging clinical trials in-house instead of sending some of the processes to an external site.

When several sites are involved in a Phase 1 trial, it complicates the process and often necessitates separate ethics approvals onsite. A reputable CRO stays up to date with industry regulations and can provide useful guidance about them to sponsors and other clients. By far, the biggest advantage to using a company with a clinical trial site in Canada is shifting the FDA Investigational New Drug Application interaction until after you have gathered early phase clinical data.

Unlike in the U. Instead of enduring the lengthy IND process in the U. They can get their individual studies approved more easily without needing to provide so much preclinical and manufacturing data, as the focus is less on the program as the safety of the protocol.

This enables companies to put off interacting with the FDA until a later date when they have more complete data. It shifts the conversation from what the FDA requires for a safe first in human study to what the expectations are for the Phase 2 studies.

Furthermore, Health Canada is considered by many companies to be very accommodating, as it will offer recommendations for resubmission and work constructively to get a study approved. There are some financial benefits to using a CRO with a Canadian clinical site, as well. In fact, our Chief Scientific Officer, Dr. John Oldenhof, has almost 20 years of pharmacology experience and has overseen more than early phase and HAP and abuse deterrent assessment studies.

We have an industrious, entrepreneurial spirit and possess the nimble dexterity to adapt, pivot and problem-solve to suit client needs, delivering high-quality results quickly and accurately.

Our clinical centers are in Toronto, Ontario and St. Louis, Missouri, enabling sponsors to utilize resources in both Canada and the U. To learn more about the services we provide and our talented management team , visit our website or contact us today. Clinical Trials are divided into 4 phases. Phase 1 and 2 trials constitute early phase trials, Phase 3 and 4 research studies are late-phase trials.

The primary objective of Phase 1 studies is to determine the correct drug dosage by evaluating drug safety and determining if there are any side effects. Phase 1 trials are conducted in healthy volunteers. Phase 2 studies also study the safety of a drug but focus on evaluating its effectiveness. These studies can be conducted in healthy volunteers or in individuals who have a certain disease or condition.

A Clinical trial is a process which is performed to determine whether an investigational drug, device or therapy is safe and effective. In early phase research i. Phases 1 and 2 , the safety and effectiveness of the drug will be evaluated in healthy volunteers.

An investigational drug can also be called an experimental drug and is being studied to see if your disease or medical condition improves while taking it. Scientists are trying to prove in clinical trials:. In order to evaluate the drug profile, we need to understand its pharmacokinetics. This is essentially how the body reacts to a drug after its administration through the mechanisms of absorption, distribution, as well as the metabolic changes.

Therefore, blood draws are collected at various time points to better understand this mechanism. Each study requires a specific number of blood draws and total blood volume. These values will be provided to you and clearly stipulated in the informed consent form ICF. The amount of blood that will be taken is outlined in the ICF. As every study is testing an investigational product, there may be side effects.

You will be provided with a list of side effects that have been reported in previous trials if any , so you can make an informed decision whether or not to participate in the trial. During the trial you will be required to immediately inform clinic study staff of any adverse effects that you are experiencing.