Principal Investigator

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.

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 fulfil the training requirements specified by the respective IRB, unless a waiver has been granted by the IRB. Training documentation (e.g., GCP certificate, Collaborative Institutional Training Initiative (CITI), study-specific training, etc) or supporting documents for waiver (if applicable) should be maintained in the study files, but it is not necessary to submit such documentation to us.

The PI should have a sufficient level of authority to supervise the clinical trial and to 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.

Regulatory obligations of a PI

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 task is delegated is qualified by education, training, and experience to perform the delegated task
• Maintain a list of appropriately qualified persons to whom significant trial-related duties 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

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.

Medical or dental decisions to be made by an investigator who is a qualified practitioner

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.

Study staff

Study staff are persons who assist the Principal Investigator (PI) in the conduct of the clinical trial. Examples of study staff may include sub-investigators, clinical research coordinators, research assistants, pharmacists etc. Study staff should be adequately qualified (by education, training and experience), informed about the protocol, and delegated by the Principal Investigator.

The roles, responsibilities and signatures of all study staff should be captured in a signature sheet. Curriculum vitae, financial disclosure forms and training documentation should be maintained on file. Refer to your relevant Institutional Review Board (IRB) for minimum training and financial disclosure requirements.

It is ideal for all study staff to be delegated to be part of the study team. A pragmatic and reasonable approach may be considered for large teams (e.g. radiologists, nurses, pharmacy technicians). This involves the following:

• If the study procedure 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 staff in the supervisory position should be trained on the study protocol and be responsible to train the study staff under their care on the protocol and basic Good Clinical Practice (GCP). Training documentation should be maintained accordingly.
• If the study procedure is performed in accordance with standard of care, there should be documentation available on file to indicate the involvement of these departments and staff, with the authorisation of the PI. It would not be mandatory to train these staff on the study protocol, but it would be recommended to train these staff on basic GCP and training documentation should be maintained accordingly.

Note: Basic GCP training should be tailored to the needs of the staff and may include:

• Documentation, e.g. ALCOA principles (i.e. Accurate, Legible, Contemporaneous, Original and Attributable), amendments
• Record keeping
• Reporting of adverse events and non-compliances