Before a new drug comes out, years of research and testing are normally necessary to make sure that it is safe and that it does what it is supposed to.
Studies that test new drugs or combinations of drugs on people are called clinical trials.
This kind of study is also used to evaluate new approaches to procedures, such as surgery or radiotherapy, and new ways to improve the diagnosis of diseases. Their results can help improve patients’ quality of life and potentially expand lifespan.
Clinical trials are required for every medication approved by the United States Food and Drug Administration (FDA).
Fast facts on clinical trials:
- Trials are carried out to assess the effectiveness of new treatments.
- They have a number of phases to help determine what works best.
- Participants in trials may be patients with a specific condition or healthy volunteers
- Trials are carried out on animals first, meaning doctors have a good expectation that the product being tested is safe.
No treatment can cure all patients. Many treatments and drugs also have adverse effects, so researchers are always looking for better ways to treat diseases.
Clinical trials are vital to understand what type of medication or procedure is best for what type of patient at what point in time.
Without results from carefully conducted trials, new therapies may not be accepted for use, because there would be no proof that they work better, faster, or safer than other options.
A number of different organizations, agencies, and companies may be involved in a single clinical trial. For example, a team of researchers might guide the study, while resources and funding may come from a public health agency, a research organization, a pharmaceutical company, or a combination of the three.
The person who manages a clinical trial is known as the principal investigator (PI), often a medical doctor with considerable experience in research.
The PI leads the research team, which consists of other doctors, scientists, nurses, psychologists, and other medical and research professionals.
A range of specialists contribute to the design of the clinical trial. They work together to analyze, interpret, and present the results.
Each clinical trial has a master plan, called the protocol; the PI prepares this document, and it includes information, such as:
- who is eligible to take part
- how many people will be involved
- what type of information is taken – for instance, blood or stool samples
- detailed information about the treatment plan
Clinical trials involve a series of steps, called phases. Each phase aims to answer a specific set of questions and increase understanding of the new treatment, before it is approved or recommended for routine use.
Phase 1 clinical trial
The first studies in humans are called phase 1 trials. The purpose of the phase 1 trial is to determine the safety of a medication. Small numbers of patients or healthy volunteers participate. Phase 1 trials can help to answer questions, such as, what dose of the drug is likely to be effective and what side effects might occur.
Phase 2 clinical trial
Phase 2 trials involve larger numbers of patients. This stage focuses more specifically on how well the treatment or procedure works in the target population. Phase 2 trials may look at particular situations or groups of patients.
Phase 3 clinical trial
- Phase 3 trials involve large numbers of patients. At this stage, researchers compare the effectiveness and safety of the new treatment with that of the standard existing treatment.
- Large phase 3 trials may demonstrate the benefits a new drug compared with existing treatments. If so, the results can be presented to regulatory authorities, which may grant a license to market and sell the drug.
Within each phase, the scientists will make an effort to ensure that the results are not influenced by bias. In other words, they want to make sure that the results they are getting are due to the drugs and not due to other factors.
Some of the steps they will take include:
Comparison groups – participants are split into groups so that a new drug can be compared to an older drug, for instance. Sometimes, a control group will be used; these individuals receive no drugs and will be compared with the group that are taking the new medication.
Randomization – usually, a computer program randomly assigns each participant into a different group. This ensures that people are split randomly.
Masking – individuals who take part in the trial and those who are running it are not told whether they are receiving a new drug, an existing treatment, or a placebo (a sugar pill, for instance). This way, expectation cannot interfere with the outcome of the trial. This may also be referred to as a “double-blind” trial.
New treatments or strategies need to be evaluated for what works best in certain illnesses or groups of people, so sometimes people are invited to, or offer to, participate in clinical trials.
If a person meets the protocol requirements, they are eligible to enroll. Eligibility criteria will vary from trial to trial but often there are criteria around:
- stage of disease
- other medications that are being taken
- other previous or existing conditions
- existing complications, if any, from the disease in question
The organizers will then provide additional information about participating. This information will outline the risks and benefits that people can expect if they participate.
The benefits of participating in clinical trials may include payment, but not always. Some trials provide medications, services, or both for no cost to those who enroll.
If the trial involves payment, amounts will vary depending upon how much detail needs to be collected and how much of the participant’s time it takes up. For instance, a study that requires the participant to stay over night will often pay better than one where only an hour or two of time is needed.
The United States’ National Institute of Health provides information about clinical trials in each state.
Anyone who decides to participate in a clinical trial should first request a clear explanation of the purpose of the trial and the role of each sponsor.
Protecting participants’ rights
Before a clinical trial can start, the doctors concerned have to explain what they wish to study and why, and how they plan to study it.
They must present this to a supervisory board of other doctors, called a Review Board or Ethical Committee.
Each clinical trial conducted in the U.S. has an Institutional Review Board (IRB).
The review body has to ensure that the trial is ethical, that the rights of participants are protected, and that the highest standards of clinical practice will be observed.
The IRB reviews the clinical trial protocol, and must approve it before the trial begins.
The Office for Human Research Protections helps to protect the rights, welfare, and well-being of the people enrolled in a clinical trial.
The trials are conducted in a medical care setting fully equipped and staffed for any emergency that might arise.
Even the most ethical and carefully planned trial of new chemicals designed for human use has risks, and sometimes things do go wrong.
To minimize the risk, new chemicals are first tested in mice and rats. Then there are tests for bacteria toxicity, called Ames tests. After that are tests for human cell culture toxicity.
Next, the product is normally tested in healthy volunteers, starting with single doses that increase in quantity.
If there are no issues, volunteers will take multiple, increasing doses, before the product is tried in a few people with the targeted illness.
Each step is carefully planned and reviewed before the next step is taken.
Nevertheless, even with all these layers of oversight, clinical trials can sometimes uncover unexpected side effects, interactions, or reactions.
New strategies, devices, or treatments may turn out to offer no benefit, or they may cause unexpected adverse effects.
For this reason, by the time humans participate in a trial, the scientists must be as sure as they can be that it is safe.
This is why the process of development is so long, and why the rules about trials are so strict.
Clinical trials are vital in improving and advancing medical care, to maximize effectiveness, and minimize risk.