Clinical trials are defined by the World Health Organization (WHO) as “a type of research that studies new test and treatments and evaluates their effects on human health outcomes”. When we talk about clinical trials, we are talking about research being carried out in human subjects. Developing a clinical trial involves a lot of time and effort, and there is a lot of pre-clinical work that needs to be done before we can start thinking about testing a drug on humans.
Pre-clinical development
First, we need to understand the biology of a disease, what causes it, and what its effects are. With this information, possible targets to treat or cure the disease are identified. When a drug is designed, it is created to attack or have an effect on these targets, and laboratory tests are done to make sure that the drug is working where it should.
The next step will be animal testing. During these tests, we look to see if the drug works where it should in the animal, and if it has an effect on the disease we are testing. We also see if there are any side effects, and what levels of the drug would be toxic to the animal. This is important to know what possible doses could be used in humans. Even at this stage, the type of studies and the type of animal they have to be used are regulated. There are some standard experiments that have to be done, and then specific ones that will depend on the type of drug, and what it is going to be used for.
Clinical development
Clinical development starts with identifying what we need to measure, and how we need to measure it to be able to say that our drug works. Regulatory Agencies have different guidelines on how to design a clinical trial, depending on the type of drug, and its use.
It is also important to mention that there are different phases in clinical development, each with its own characteristics and requirements. For more information on the different phases in clinical trials, click here.
Relevance of clinical trial design
Why is clinical trial design such an important step? A suitable design ensures that you collect the right information in the right way and will make the whole process of the clinical trial simpler, improving the chances of the trial being approved. Within clinical trial design we have to decide:
- Are we going to study only one drug (non-controlled), or are we going to compare it to something (controlled)? We could compare it to placebo, or to another drug already being used for that disease or indication for example.
- If we are comparing our drug to something, how are we going to decide which participant receives which drug? Are we going to divide them randomly (randomized), or are we going to let the participant/investigator decide, or will it depend on when they join the trial (non-randomized)? Will the participants be divided equally, or do we want there to be a different number of participants taking each drug?
- If we decide to compare our drug to something, will the participants know what drug they are taking? If they don’t, it would be a blinded study. If they do, it would be an open label study. There are many levels of blinding, and which one is used depends on the trial design.
- If we are comparing our drug to something, will the participants only take one of the drugs? Will they switch to the other drug halfway through the study? Will they first be divided and take different drugs for part of the study, and then take only one drug for the rest of the study?
- How many participants do we want there to be?
- What kind of participant are we going to look for? We need to decide what criteria we want someone to meet to participate (inclusion criteria), and what criteria we don’t want someone to meet to participate (exclusion criteria). For example, we don’t want to include men in a study where you are looking at women’s contraceptives.
- What medical tests and exams do we need to do and when do we need to do them?
The study startup process
Now that we have the study designed and approved, we have to decide where it will be carried out. Clinical trials are usually carried out in clinics or hospitals and are referred to as Sites. It is very important to select the right sites for your study, as the site will be in charge of finding participants, and the day-to-day interaction with them.
You also need to do a feasibility analysis to make sure that the site is capable of doing your trial. Part of this will be evaluating their availability, manpower, their facilities, their experience. We have to ask ourselves:
- Are they capable of seeing and tending to all the participants you want?
- Do they have the equipment and the technicians needed to be able to do the tests and exams you want to do?
- Have they been a site for other clinical trials? Do they have the right training and certification for your clinical trial?
Once you have selected your sites, and have done all of the paperwork, you can submit your clinical trial for approval.
Clinical trial approval
Before carrying out a clinical trial, the trial design, the proposed sites, and many other documents must be sent to and approved by the Regulatory Agency (RA) and the Ethics Committee (IEC/IRB) These entities will send feedback on how to improve the study, and if any changes need to be made to ensure participant safety. If they send their approval, the clinical trial can be carried out.
How to conduct a clinical trial
The next step in carrying out a clinical trial would be Recruitment. During this stage, the site actively looks for people to participate in the study, advertising campaigns might be used, and participants are recruited to the trial.
When someone is interested in participating in the trial, they go through Screening, which is when the investigator gives them all of the information on the study (what tests will be done, what is required, etc.), and answers any questions. The investigator will ask the person questions to see if they are eligible to participate in the study. If the person decides to join the trial, they sign an Informed Consent Form (ICF), stating that they accept the terms and conditions of participating in the trial.
Once the ICF is signed, and it has been confirmed that the participant meets all the inclusion criteria, and none of the exclusion criteria, they are then Enrolled in the clinical trial, given the study medication, and the study is carried out. The participant will be monitored by the site throughout the trial.
Drug development, from target identification, pre-clinical research, clinical research, all the way to drug approval and marketing, usually takes around 15 years. It is a very lengthy and expensive process, but developing new treatments and cures would not be possible without the participation of volunteers in clinical trials. We encourage our readers to learn more and help us spread the word about clinical trials.
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