Introduction to Clinical Trials
- What is a clinical trial?
- What are the different phases of clinical trials?
- What are the different types of clinical trials?
- Why are clinical trials important?
- Why are clinical trials conducted?
- How are clinical trials regulated in Singapore?
- Who can participate in a clinical trial?
- Who can conduct a clinical trial?
- Who can sponsor a clinical trial?
- Where is a clinical trial conducted?
- What happens during a clinical trial?
- How long do clinical trials usually last?
- What are some of the possible risks of participating in a clinical trial?
- What are some of the potential benefits of participating in a clinical trial?
- How are participants protected?
- What is “informed consent”?
- What questions should a participant ask an Investigator during the informed consent process before deciding to participate in a clinical trial?
- What are the rights of a participant?
- What are the responsibilities of participating in a clinical trial?
- Who can I contact if I am interested in participating in a Phase I clinical trial on healthy volunteers?
- Who can I contact if I am interested in participating in a clinical trial on a particular illness?
- Where can I find out more information about clinical trials conducted in Singapore?
A clinical trial is a research study conducted to investigate new treatments such as a new drug compound 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 in human, extensive laboratory testing are done to identify promising compounds and toxicological (safety) tests conducted to determine possible risks. The treatment with the most promising results is then moved into clinical trials. Research in humans takes a cautious and progress in a sequential or phase approach.
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 in 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 III trial.
- Phase 3: Clinical trials that are conducted in 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.
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 designed to improve medical knowledge related to the treatment, diagnosis and prevention of illnesses. Clinical trials translate results from basic scientific research and promote an evidence-based approach to healthcare leading to better health outcome. The results of clinical trials can make a difference in the care of patients by providing information about the benefits and risks of new therapeutic, preventative, or diagnostic products or interventions. Clinical trials also can contribute invaluable information about the benefits and safety of existing therapies, providing doctors and patients with reliable information for choosing between alternative treatments.
Clinical trials are an essential part of the regulatory process. They provide the basis for the development and marketing of new drugs, biological products, and medical devices. The data collected from clinical trials to provide the evidence to show that the product is safe and effective is used to support product registration or marketing authorisation of new medicines and medical devices.
The Health Sciences Authority (HSA), through its Health Products Regulation Group, regulates the conduct of clinical trials in Singapore 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 study. The ethics approval is from the hospital’s Institutional Review Board (IRB). In order to receive regulatory approval from HSA to conduct clinical trials here, 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 participants.
Companies or research institutions sponsoring clinical trials and doctors conducting them are expected to abide by the protocol, applicable clinical trials and clinical research material regulations, ICH E6 Good Clinical Practice (GCP) Guidelines and Standard Operating Procedures (SOPs). The ICH E6 GCP Guidelines is based on international ethical and scientific quality standards. The conduct of clinical trials in accordance with the principles of GCP helps ensure that the participants’ rights and interests are adequately protected and they are not exposed to undue risk, and that safety and efficacy data generated from the research are valid and accurate.
A clinical trial is conducted in accordance with a research plan called a protocol that has been designed to address the research question and safeguard the rights, safety and well-being of participants. The protocol outlines the eligibility criteria thereby defining the population being researched upon for the clinical trial. The eligibility criteria usually define the age, gender, type and stage of an illness, previous treatment history, and other medical conditions. Participants must sign an informed consent form before they can be screened for eligibility assessment for a clinical trial.
8. Who can conduct a clinical trial?
A clinical trial is conducted by an Investigator who must be a locally registered doctor or dentist. In Singapore, clinical trials are usually conducted by senior doctors or specialists in their field of practice, and performed in hospital settings. The Investigator usually works together with a team of healthcare professionals like doctors, nurses and pharmacists to conduct the clinical trial.
Clinical trials can be sponsored by pharmaceutical companies, medical technology companies, biotechnology companies, hospitals and other funding bodies.
A clinical trial is usually conducted at hospitals or clinics. The location depends on who is conducting the clinical trial.
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.
Depending on the trial, participants 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. Participants are allocated to random groups to ensure each group has a mix of participants to reflect the requirements of the trial. The team will check participants’ condition before the trial and administer the treatment in accordance with a set of specific instructions to be followed. During the trial, the trial team will schedule several clinic visits to conduct tests and check on the participants’ well-being. Constant communication between the participants and trial team is vital would ensure the safety and proper conduct of the clinical trial. At the end of the trial, the results should be made known to everyone so that participants will be able to obtain information and make decisions for their well-being.
The length of a clinical trial depends on what is being researched upon. Participants are informed about the duration of participation in the clinical trial during the informed consent process.
Clinical trials are designed to minimise the risks to all participants. While some risks are unavoidable because of the uncertainty inherent in medical research studies involving new treatments, the ethical and regulatory review together help to ensure that the specific aims, problems and risks or benefits of a particular clinical trial are thoroughly considered and that the chosen options are scientifically sound and ethically justified. Participating in a clinical trial may be demanding and time consuming. All potential participants are strongly encouraged to learn as much as possible about clinical trials and understand the benefits and risks associated before participating. The regulation requires investigators to give prospective participants complete and accurate information about what will happen during the trial. Participants must sign an informed consent document before joining the study. This informed consent is part of a process that ensures a prospective participant in a clinical trial understands what known risks might be associated with the study, and whether there are potential, but as yet unknown risks that may be associated with the product being studied. This information would enable a prospective participant to make an informed decision whether or not to enter a clinical trial.
Aside from phase 1 clinical trials, studies are conducted on research treatments that have been shown to present some level of desirable effects and where previous results 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. Participating in a clinical trial is one approach for eligible patients/volunteers to gain access to potentially new research treatments. In Singapore, the investigators conducting clinical trials are specialists in the disease area being studied. By participating in clinical trials, the patients can have access to expert medical care. The participants can also get actively involved in their health care, and help others by contributing to medical research.
Clinical trials are regulated to ensure that participants in clinical trials are protected (see question 6). An important safeguard measure to ensure safety of participants is through the informed consent process.
An informed consent must be obtained from a participant prior to the conduct of any study procedure. Informed consent is a process whereby investigators provide a potential participant with information about the research study. It is the investigator’s responsibility to ensure that the participant has been adequately informed about the clinical trial, understood the subject responsibilities, risks, benefits and alternative treatments to the clinical trial, and voluntarily agreed to participate in the clinical trial. The participant should be given ample time to consider participation in the clinical trial and have his / her questions addressed in a satisfactory manner before agreeing to participate in the clinical trial. 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.
Anyone interested in participating in a clinical trial should know as much as possible about the study and feel comfortable asking the study team questions about the clinical trial, the related procedures, and any expenses.
The following questions might be helpful during such a discussion. Answers to some of these 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?
A participant has the following rights:
- Right to be informed about the clinical trial including the objective, study procedures, risks, benefits, compensation and alternative treatments.
- Right to ask questions about the clinical trial.
- Right to make an informed decision to participate in a clinical trial without force, fraud, deceit, coercion, duress or undue influence.
- Right to withdraw from a clinical trial at any time without compromise of medical care.
Participants should undergo all the study procedures outlined in the informed consent form and follow the advice given by the study team.
- National University Health System Investigational Medicine Unit
- Singhealth Investigational Medicine Unit
- Changi General Hospital Clinical Trials and Research Unit
- Lilly-NUS Centre for Clinical Pharmacology
For HIV-related research, please contact:
Communicable Disease Centre (CDC), Tan Tock Seng Hospital
For cancer-related research, please contact:
Haematology-Oncology Research Group (HORG)
- National University Health System
- National Skin Centre
- Tan Tock Seng Hospital
- Institute of Mental Health
- Khoo Teck Puat Hospital
- Singapore General Hospital
- KK Women’s and Children’s Hospital
- National Cancer Centre
- National Dental Centre
- National Heart Centre
- Singapore Eye Research Institute
Refer to the Clinical Trials Register for more information.