- What is a clinical trial?
- Natural history studies
- Phases of clinical trials
- How are trials conducted?
- How are participants protected?
- Why participate in trials?
- A word of caution about unethical clinical trials
A clinical trial is a research study conducted in human volunteers to assess whether a new intervention is safe and effective for a specific condition. The intervention tested can either be a new drug, a device, a procedure or even changes to a participants’ behaviour (such as dieting). It is normally tested against a current standard treatment, a placebo or no intervention.
Trials are conducted by research teams led by a principal investigator, who is usually an expert in the condition and the intervention being studied. The trials may be conducted in only one centre (single-centre trial) or in multiple centres (multicentre trials). Credible trials are strictly regulated and have obtained ethical approval. Funding of clinical trials can come from a variety of sources. These include pharmaceutical companies, medical research councils, universities, charities or a combination of these sources.
Prior to testing a new intervention for a particular condition, scientists would first need to gain a better understanding of the natural disease course to identify potential treatment targets, the optimum timing to commence treatment and markers to assess treatment effectiveness. Trials that provide these data are called natural history studies. Participants of natural history studies are not given any interventions apart from the standard treatment that they are already receiving from the usual clinical team.
These are studies performed in the laboratory on animals or cell models to find out if a particular drug or procedure is likely to be useful for a specific condition. The dosage and toxicity levels of the new treatment is studied in this phase. Robust data on the safety and effectiveness of the intervention must be proven at this stage before proceeding to human testing.
Phase one clinical trials allow the research team to establish the potential effect the new treatment has on humans and its safety. It usually involves a small number of participants, with 6 to 10 healthy volunteers or blind patients with no ability to detect light.
Phase two clinical trials are designed to evaluate the safety and efficacy of the new treatment at different dosages. It normally has more participants than phase one, with about 20 to 50 participants.
If the tested treatment is shown to be effective in phase 2, a phase three clinical trial is conducted on a larger number of participants (100-200) to confirm its safety and efficacy. If the trial is successful at this stage, regulatory approval for the drug or procedure will be sought and once this is granted, the drug or procedure becomes a treatment available for all patients.
Phase four clinical trials are also known as post-authorisation safety studies (PASS). This is conducted after the new treatment has received regulatory approval and being used routinely in the clinical setting. It serves to evaluate the long-term side effects of the treatment and its real-world effectiveness.
When designing a clinical trial, the Health Research Authority (HRA) recommends involving the public and patients so that the trial is more in line with the public’s interest and concerns. The HRA has highlighted several points about the importance of public involvement in study design and how it can help in developing high quality research. These include:
- Research are made more relevant (patients and the public are able to benefit more from the results)
- Help in determining if certain aspects of the trial are acceptable (especially in high risk, controversial or sensitive research)
- Improving the consent process (making it easier for potential participants to understand the trial and the potential risks and benefits)
- Improving the experience of participants (ensuring practical arrangements such as questionnaires, appointment duration and travel reimbursements etc. are appropriate)
- Improving the communication and dissemination of research findings to participants and the general public (providing regular updates in an understandable and accessible format)
After the study design is finalised, the team conducting the trial then draws up a research plan, also known as a protocol to outline how the study should be conducted and also to safeguard the wellbeing of participants. It usually contains the following:
- Reason for conducting the study
- Who can participate in the study (also known as the eligibility criteria and exclusion criteria)
- Location(s) of where the study is being conducted
- Number of participants needed
- Allocation of interventions for participants
- Length of the study
- Schedule of tests, procedures, or drugs and their dosages
- Data that will be gathered from the participants (outcomes) and the collection method
Once the study protocol has been reviewed and approved by an ethics committee to make sure it will not cause harm to participants, the research team then starts recruiting participants and conduct the trial according to the protocol. Adhering to a protocol ensures that the data gathered is robust and reliable.
A member of the research team conducting the trial usually has a thorough discussion with potential participants, particularly outlining the risks and potential benefits of the study. This discussion also allows potential participants or their relatives to ask questions. Participants are then provided with patient information leaflets for further reading and given time to consider. This process is called informed consent. Even if a consent form has been signed, it is not a binding contract and participants can withdraw from the study at any point.
In the UK, clinical trials involving a drug, biological product or medical device must be reviewed and authorised by a government agency called the Medicines and Healthcare products Regulatory Agency (MHRA). The MHRA inspects the involved study sites to make sure that trials are conducted in line with good clinical practice.
In addition, approval by one of more than 80 National Health Service (NHS) Research Ethics Committees (RECs) across the UK is compulsory before a clinical trial can begin. The committee’s main goal is to protect the welfare and safety of research participants. Each committee consists of up to 15 members where a third are “lay”. This means that they do not have a professional interest in the research area and are not registered healthcare professionals. The RECs are independent of research sponsors (the organisation responsible for the management and conduct of the trial), funders and the researchers involved.
(1) Contribute to medical knowledge
Results of trials can be used to inform the wider medical community about the effects, risks and benefits of a specific drug, procedure or any other interventions. It may stimulate further studies which could lead to the discovery of a new treatment.
(2) Access to cutting edge therapies
Most inherited eye disorders have limited or no treatment options. Participating in trials allow patients access to new therapies that could potentially be beneficial.
(3) Receiving expert care
Research teams involved in clinical trials are normally led by experts in their respective fields. As researchers need to adhere to the trial protocols strictly, participants tend to have scheduled and more detailed follow-ups. However, this means that each follow-up appointment might be more time consuming than your standard clinic appointment.
Most clinical trials are listed in a trial registry which can be easily accessed online. One of the more popular registries, ClinicalTrials.gov is a useful resource provided by the US National Library of Medicine.
However, it is important to note that presence of a study on ClinicalTrials.gov does not mean that the study has been evaluated by an ethics committee or given approval. Several women went blind after an unproven intervention, listed as a “stem cell trial” on ClinicalTrials.gov.
If you are interested in a particular trial, it is important that you seek advice from your doctor on whether they think it is reputable and ethically approved.
- NHS Health Research Authority. Research Ethics Committees overview. https://www.hra.nhs.uk/about-us/committees-and-services/res-and-recs/research-ethics-committees-overview/. Published 2020. Updated 4 February 2020. Accessed 24 June 2020
- Kuriyan AE, Albini TA, Townsend JH, et al. Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD. N Engl J Med. 2017;376(11):1047-1053