A Principal Investigator (PI) is a qualified practitioner or qualified pharmacist, who should be qualified by education, training and experience, and has adequate resources to conduct a clinical trial.

• A qualified practitioner is a locally registered medical practitioner under the Medical Registration Act or a registered dentist under the Dental Registration Act.

• A qualified pharmacist is a locally registered pharmacist under the Pharmacists Registration Act, who holds a valid practising certificate and is in active practice as defined in the Pharmacists Registration (Practising Certificates) Regulations. Please refer to the Ministry of Health's Guidance on Pharmacists as Principal Investigators for further details.

Note:

• The PI should have a sufficient level of authority to supervise the clinical trial and make independent medical decisions during the trial. The level of supervision should be appropriate to the nature of the trial and the trial population.
  • If the PI has a conditional registration with the Singapore Medical Council which requires the doctor to "work under supervision", the doctor would be required to submit a statement from the doctor's supervisor indicating support for the doctor's involvement as the PI of the study, as part of the clinical trial application to us.
• For clinical trials assessing investigational products in specialised therapeutic areas, the PI should be at least an Associate Consultant (AC) in the specialised therapeutic area. This is because such clinical trials usually involve complex diagnostic evaluation of the disease condition, or study procedures that require specialised skills. A suitably qualified AC and above would have sufficient training and experience to conduct such clinical trials properly, as well as to handle unforeseen adverse events or difficulties during the conduct of the clinical trial.
• It may be acceptable for the PI of a clinical trial of a locally registered therapeutic product to be a general practitioner, if the product is generally used by a general practitioner in clinical practice.

The PI should be trained in Good Clinical Practice (GCP), the study protocol and any other study-specific procedures prior to conducting the clinical trial.

• Training documentation (e.g., training logs, certificates, CVs) or supporting documents for waiver (if applicable) should be maintained in the study files accordingly.
• Refer to your relevant Institutional Review Board (IRB) for other minimum training requirements.

Responsibilities of a PI

The PI is responsible to ensure that clinical trials are conducted in compliance with the protocol, standard operating procedures, GCP and applicable regulatory requirements.

The regulatory obligations of a PI conducting a clinical trial are as follows:

• Conducts clinical trials in compliance with the protocol, applicable regulations, the principles of GCP and the standard operating procedures relevant to the clinical trial
• Conducts clinical trials at location(s) specified in the clinical trial application
• Ensures that all medical/dental care and decisions relating to the trial participants are the responsibility of an investigator who is a qualified practitioner
• Ensures that any individual to whom a trial-related activity is delegated is qualified by education, training, and experience to perform the delegated trial-related activity
• Maintain a list of appropriately qualified persons to whom significant trial-related activities have been delegated
• Ensures that informed consent requirements are complied with
• Keeps adequate essential trial documents for the specified period
• Declare every financial interest, including that of any person assisting the PI, to the IRB
• Reports serious adverse events within stipulated timelines to sponsor, and IRB if required
• Ensures that there is a system of traceability established and maintained at the trial site, if the trial involves a Class 2 CTGTP

Medical or dental decisions to be made by qualified practitioners

The PI must ensure that an investigator, who is a qualified practitioner, is responsible for the medical or dental care given to the trial participants and for all trial-related medical or dental decisions made on behalf of the trial participants. Examples of these decisions include the following:

• Obtaining medical history
• Confirming trial participant eligibility
• Assessing clinical response to an investigational therapy
• Providing medical care to trial participants during the course of the clinical trial
• Performing and reviewing safety assessments (e.g. physical examinations, vital signs, safety laboratory results)
• Evaluation and reporting of adverse events

Note: Trial participant eligibility should be reviewed based on the protocol. The practice of enrolling trial participants into a study based on "protocol waiver" is discouraged as there may be implications to the validity of the data, if trial participants who have not fulfilled the eligibility criteria was enrolled.

Delegation and training of study staff

Study staff are persons who assist the PI in the conduct of the clinical trial. Examples of study staff may include sub-investigators, clinical research coordinators, research assistants, pharmacists etc.

Every person conducting a clinical trial must do so in accordance with the principles of GCP, and should be delegated by the PI and adequately qualified (by education, training and experience).

The PI should maintain a record of study staff to whom the PI has delegated significant trial-related activities (e.g., informed consent, eligibility assessment, investigational product management, key efficacy and safety assessments, etc). Such records should capture the roles, trial-related activities and signatures of the delegated staff.

• In situations where trial-related activities are performed in accordance with routine clinical care, delegation documentation may not be required. However, there should be documentation available on file to indicate the involvement of the relevant departments and staff, with the authorisation of the PI.
• In situations where large teams (e.g., radiologists, nurses, pharmacy technicians) are involved in trial-related activities, a pragmatic and reasonable approach may be considered. For example, if the trial-related activity is performed in accordance with the protocol, the PI may delegate a staff of supervisory position (e.g., head of department, nurse manager or pharmacist) to be part of the study team. The PI should ensure that the staff in the supervisory position is trained on the study protocol and the study staff under their care are trained on the protocol. Training documentation should be maintained accordingly.

The PI should ensure that study staff to whom the PI has delegated significant trial-related activities are appropriately qualified and supervised, and adequately informed about the protocol and their delegated trial-related activities.

• Delegated study staff should complete appropriate trial-related training (e.g., study-specific training, GCP, applicable SOPs) to enable them to perform their delegated trial-related activities in accordance with GCP, especially if these entail activities that go beyond their usual training and experience in routine clinical care.
• Training documentation (e.g., training logs, certificates, CVs) should be maintained in the study files accordingly.
• Refer to your relevant Institutional Review Board (IRB) for other minimum training requirements.

Change of PI

An amendment application for change of PI must be submitted to us and the IRB prior to implementing the change. This is also applicable to change of PI for a suspended clinical trial.

As the PI should have sufficient time to properly conduct and supervise the clinical trial, we recommend a change of PI if the PI is away on extended leave for more than four months.

It would be recommended to complete an end date for all study staff on the current Signature Sheet, and complete a new Signature Sheet for all study staff to be authorised by the new PI.