Clinical trials use defined procedures and little variation to determine a drug’s effects effectively. It includes randomization (possibly with stratification), adherence to intent-to-treat analyses, blinding and prospective evaluation. Clinical trial results are based on measurable values called endpoints, which must be clinically relevant and interpretable, sensitive to the effect of the treatment under study, practical and affordable to measure, and unbiased.
During clinical trials, patients can sometimes receive placebos instead of experimental drugs. It is especially common in phase I trials designed to determine whether a drug has any pharmacological effects. Placebos are inert substances or treatments that do not contain any active ingredients. Despite their inactive nature, placebos can still produce measurable physical results on a patient. This phenomenon is known as the placebo effect. Placebos have been shown to alter a person’s perception of their symptoms, reduce stress hormone levels and stimulate the release of the body’s natural pain relievers, such as endorphins.
Researchers often use what is called a double-masked study. It means that neither the participants nor their doctors know who receives a placebo or an experimental medication. It can help to prevent bias, which is caused by subtle factors that are unrelated to the trial’s protocol. The number of participants in a clinical trial can also significantly impact the outcomes in clinical trials. Greater statistical power will be possible with a bigger sample size, which is crucial when evaluating the efficacy of a novel treatment. However, it will also increase the cost of the study.
During a clinical trial, the participants are carefully monitored to ensure they are not being put at unreasonable risk. The sponsor of the trial, the local site investigators, and (if the study involves a marketable drug or device) the FDA all have responsibilities in this area. Every clinical trial has eligibility requirements for participants. These rules are called eligibility criteria. They are based on age, sex, and the type and stage of the disease being studied. Some eligibility criteria are very strict, and not everyone wanting to participate can do so. The study’s design is a key factor in ensuring a clinical trial’s safety. It includes minimizing potential bias through randomization and control groups and careful selection of participants to help ensure that results are not affected by factors unrelated to the intervention under test.
The choice of whether a trial is designed to test for superiority or equivalence is important because it affects the size of the sample and the statistical power required. The number of participants recruited will also influence the trial costs and the time needed to complete the study. Sponsors of a clinical trial or contract research organizations working on their behalf recruit volunteers and patients for the study through various channels, including patient databases, newspaper and radio advertisements, posters in places where the target audience normally goes, and personal recruitment by the investigators. The researchers then follow the guidelines laid down by each study’s protocol, which is the exact plan for what the researchers will do in the trial.
Endpoints in a clinical trial measure the effectiveness of an intervention and help identify whether it is safe and effective. They must be clearly defined and measured in an unbiased manner. They must also be clinically relevant and appropriate for the research question. In addition, they should be sensitive enough to detect an expected difference between groups. They should be straightforward to measure, clinically relevant, and unaffected by other elements like illness severity or co-morbidities.
Clinical trials often use composite endpoints, which are multiple measurements combined into a single measure. These may include time to event, progression-free survival, or response duration. These are often more useful than individual clinical endpoints because they reduce the need for long follow-up periods and allow researchers to get a better sense of the overall effect of a treatment in a shorter amount of time. However, it is important to ensure that the components of a composite endpoint occur with similar frequency and are not affected by confounding variables. It will avoid the bias resulting from informative censoring, which occurs when some of the events in a trial are missed due to loss to follow-up, death from a cause unrelated to the study, or other reasons.
Clinical trials are also sometimes designed using surrogate endpoints, which are measures that predict a clinically definitive endpoint and take less time to observe. A common example is measuring blood pressure to predict stroke risk. However, various factors, including co-morbidities and other medications, can bias these measurements.
A dose is the amount of a drug or other treatment a person will receive during a clinical trial. Depending on the study’s goal, a clinical trial may use different dosages. The study may be designed to test the safety of a new medication or determine how much medicine is needed to treat a disease. In traditional phase I design, a primary objective is to estimate an optimal dose based on safety endpoints. However, these assumptions may not be appropriate for molecularly targeted agents, immunotherapies, or radiotherapy studies developed as single-agent or combination therapies. A primary objective based on efficacy endpoints might be more suitable for these types of trials.
During phase I, researchers will give different doses of the experimental drug to healthy volunteers or people with the disease being studied. The amounts will be increased gradually to find the most effective and safe dose for the drug. These doses are called cohorts. Phase II trials aim to see if the experimental drug or therapy treats a specific disease in larger groups of people. The group sizes in these trials are usually much larger than the groups in Phase I. The researchers also try to determine if the treatment is safe in large groups of patients.