What is a clinical trial
A clinical trial is a research study conducted to investigate new treatments, such as a new drug compound or an existing therapy, in human volunteers or research participants. Each clinical trial is designed to learn about a potential treatment and its effect on humans.
Before a new treatment is tried on humans, extensive laboratory tests are done to identify promising compounds, and safety tests are conducted to determine possible risks. The treatment with the most promising results is then moved into clinical trials.
How are clinical trials regulated
Clinical trials in Singapore are regulated under the Health Products Act and Medicines Act and their subsidiary legislations. The system of regulation requires that Principal Investigators (PI) conducting clinical trials to obtain both ethics and regulatory approvals before initiating a clinical trial.
Ethical approval is provided by the Institutional Review Board (IRB) and regulatory approval is provided by us. In order to receive ethical and regulatory approval, companies must provide relevant evidence that the investigational drug is acceptably safe, and the design and conduct of the trial provide adequate levels of protection for the participants.
Types of clinical trials
Clinical trials may either be interventional or observational clinical trials.
Interventional clinical trials involve giving a participant a particular treatment in accordance with a research plan. Usually, these participants are compared to subjects who receive no treatment or standard treatment.
Observational clinical trials involve giving a participant a particular treatment in accordance with clinical practice.
Clinical trials are usually conducted in humans in the following phases:
| Phase 1
|| Clinical trials that are usually conducted on a small number of healthy volunteers with close safety monitoring. The objective is to determine whether the drug is safe for use in humans and how the drug behaves in the human body.
| Phase 2
|| Clinical trials that are conducted on a small number of patients with the illness being researched upon. The objective is to explore the therapeutic efficacy of the drug and to further evaluate its safety. A key objective of this phase is to determine the dose for phase 3 trial.
| Phase 3
|| Clinical trials that are conducted on a larger population of patients. These clinical trials help to demonstrate or confirm the therapeutic efficacy of the drug and to collect more information that will allow the drug to be used safely. These studies are intended to provide an adequate basis for submission to regulatory authorities for product registration.
| Phase 4
|| Clinical trials that are conducted to gather additional information about a drug's safety, efficacy, and optimal use. They are also sometimes known as post-marketing studies.
Note: Some clinical trials may combine more than one phase together.
What happens in a clinical trial
Before the trial
All clinical trials have different sets of eligibility criteria for participation. These criteria are usually defined by:
- Illness type and stage
- Treatment history
- Other medical conditions
The study team will check the health of the participant and screen the participant based on the eligibility criteria outlined in the research plan or protocol.
A participant who is found to be eligible will be enrolled into the clinical trial and study procedures will be conducted on the participant in accordance with the protocol.
The participant may need to have more tests performed on him/her during a clinical trial, in comparison to patients who are not participating in clinical trials.
You must sign an informed consent form before you can be screened for eligibility assessment for a clinical trial.
During the trial
Depending on the trial, you may be distributed into different treatment groups. In a controlled trial, the trial group will be given the new study treatment while the other control group will be given an existing or standard treatment.
In cases where there are no standard or existing treatments, a control group may be given a dummy treatment called a placebo.
In a randomised clinical trial, you will be randomly allocated to a treatment group. This ensures that each group has the right mix of participants to reflect the trial requirements.
The trial team will schedule several clinic visits to conduct tests and check on your well-being. Constant communication between you and the trial team is vital to ensure your safety and proper conduct of the clinical trial.
Benefits of participation
Aside from phase 1 clinical trials, studies are usually conducted on research treatments that have:
- Shown to present some level of desirable effects
- Previous results to suggest continuing its development
Hence there is generally a tendency for the trials to show positive results although failures due to lack of benefits or increased risks do occur late in the product development in large phase 3 studies.
In Singapore, the investigators conducting clinical trials are also specialists in the disease area being studied. You can then gain access to expert medical care as a participant in these clinical trials.
At the same time, you can also get actively involved in the investigators' health care, and help others by contributing to medical research.
While clinical trials are designed to minimise the risks to all participants, but may still be demanding and time consuming. Patients are strongly encouraged to learn as much as possible about clinical trials and understand the risks associated before participating, as risks are usually specific to the drug being tested and the procedures that will be performed in each study.
A clinical trial's ethical and regulatory review help to ensure that specific aims, problems and risks or benefits are thoroughly considered and that the chosen options are scientifically sound and ethically justified.
Clinical trial investigators are also required to give prospective participants complete and accurate information about what will happen during each trial.
You must sign an informed consent document before participating in a clinical trial.
Informed consent is a process whereby investigators provide a you, a potential participant, with information about the research study. It is the investigator’s responsibility to ensure you:
- Are adequately informed about the clinical trial
- Understand the responsibilities, risks, benefits and alternative treatments to the clinical trial
- Voluntarily agree to participate in the clinical trial
The participant should be given ample time to consider participation in the clinical trial and have any questions addressed in a satisfactory manner before agreeing to participate.
Signing the informed consent form and providing consent is not a contract. Participants may choose to withdraw from a clinical trial at any time without any penalty, even if the clinical trial has not been completed.
The following questions may be helpful during a discussion with an investigator. Answers to the questions are provided in the informed consent document:
- What is the purpose of the clinical trial?
- What are the study procedures required to be conducted in this clinical trial?
- What are the participants’ responsibilities in this clinical trial?
- What is considered as standard care and experimental in this clinical trial?
- Who will be responsible for medical care of the participant in this clinical trial?
- Will the participant be able to continue consulting his healthcare provider?
- Who should the participant contact in the event of any adverse events?
- What are the possible risks of participating in this clinical trial?
- What are the possible benefits of participating in this clinical trial?
- Would the participant be required to practice contraception during the clinical trial?
- What are the alternatives to participation?
- What are the costs incurred to the participant by participating in the clinical trial?
- What expenses incurred by the participant are covered by the clinical trial?
- Can the participant stop participating in the clinical trial at any time?
- Will there be compensation for research related injury?
- How will the participant’s privacy and confidentiality be protected?
- Would the participant have access to the study treatment after completion of the clinical trial?
- Who can the participant contact for any questions about the clinical trial?
Rights of participants
As a participant in a clinical trial, you have the right to:
- Be informed about the clinical trial including the objective, study procedures, risks, benefits, compensation and alternative treatments.
- Ask questions about the clinical trial.
- Make an informed decision to participate in a clinical trial without force, fraud, deceit, coercion, duress or undue influence.
- Withdraw from a clinical trial at any time without compromise of medical care.
Responsibilities of participants
You should undergo all the study procedures outlined in the informed consent form and follow the advice given by the study team.
Personal Data Protection Act (PDPA)
The collection and usage of all subjects’ data in clinical trials will be protected in order to ensure your privacy and data remain confidential. The regulatory provisions for confidentiality are outlined in Paragraph 11 of the First Schedule of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations. Please also refer to ICH E6 (R2) Good Clinical Practice Sections 2.11, 4.8.10(n, o), 8.3.21 and 8.4.3.
In addition, the sponsor should also ensure that the informed consent form is consistent with PDPA requirements. You may wish to consult the relevant IRB on the inclusion of the PDPA clause in the informed consent form.