In the topic "What is a scientific experiment?" we discussed the main properties of scientific experiments, how they are carried out, and how experimental science differs from theoretical and observational. An experiment in medicine is slightly different from a "standard" scientific experiment — this is due both to the fact that people are studied, which means ethics and responsible conduct of research are of utmost priority, and the fact that there are a huge number of pathological conditions, which means that medical experiments and scientists need more maneuverability.
Phases of a clinical trial
For a drug to be sold in pharmacies, it must be recognized as both effective and safe. To prove that a drug is both effective and safe, a long and complex series of experiments are performed. If the experiments involve humans, for example, if the drug is being studied in a small number of patients suffering from the disease and taking the drug, it is called a clinical trial. There are many phases of these experiments, which we will cover below. Prior to studies in animals, there are also in vitro preclinical studies that are done.
Before starting any research in humans, animal studies are carried out in the laboratory. If the drug works in the animals models, it may progress to what is called Phase 0. At this point, the investigational new drug (IND) will be given to healthy volunteers in doses that are significantly lower than the therapeutic dose. In these experiments, pharmacokinetic parameters are studied, including oral bioavailability and half-life. In Phase 1, doses are increased, and researchers examine dose response effects. The purpose of Phase 1 trials is to assess the safety of the drug in healthy volunteers. Zero and First phase are often combined.
Two important definitions to understand clinical trials are pharmacokinetics, the study of how the drug moves through the body (where it goes and how long it stays there) and pharmacodynamics, the study of how the body responds to the drug, and the drug's molecular, biochemical, and physiologic effects.
Once the pharmacokinetics and pharmacokinetics of an IND are understood in the healthy human body, scientists can proceed to Phase 2, in which they assess the effectiveness of the drug. This phase includes patients with the disease or condition that the drug is intended to treat, and they receive a therapeutic dose. A critical control in phase two is the placebo group, patients who receive a mock form of the drug that looks the same but does not contain the actual drug compound. The comparison of the results from the treated and placebo groups is what will allow the researchers to draw a conclusion about the effectiveness of the drug.
After completion of the second phase, the drug is often issued for registration by the relevant authorities, but it cannot be released to the market without a Phase 3 study — a long-term and large-scale confirmation of the results obtained during the second phase. Typically, in the third phase of the study, a much larger group of people is studied (from several hundred to several thousand). The objective of the third phase is to identify all possible side effects of the drug and their frequencies. The result of the third phase will be the registration dossier of the drug, which is very detailed. In addition to specific data on the drug, the dossier also describes the method of making and formulating it. This whole process must comply with GMP — Good manufacturing practice.
Finally, after Phase 3 and the official approval of the drug for sale, Phase 4 begins — the post-registration phase. At this stage, the physicians and representatives of the pharmaceutical company collect information from all of the patients taking the newly available drug. They are mostly concerned with assessing any additional side effects that become apparent in a larger population and must be added to the registration dossier and drug instructions. Despite the fact that this phase occurs after registration, it is very important, to identify serious side effects or drugs that perform unreliably so they can be withdrawn from sale. This phase helps to identify delayed side effects that may occur after the completion of the study phase. In addition, the influence of the substance on vulnerable groups (for example, elderly patients) is often studied at this phase.
Differences between clinical trials and "standard" experiments
A clinical trial is a scientific study of humans that is usually conducted to evaluate the efficacy and safety of a drug or therapy. Because of this, there are several important differences between conventional experiments and clinical trials.
- Before a study begins, the research team creates the design of the trial. Participants in a clinical trial are randomly divided into groups. A single-blind trial is one in which the researcher knows who belongs to the test group (the group that takes the drug) and who belongs to the control group (the group that takes the placebo), but the participants in the groups do not know which group they are in. A double-blind trial is one in which an external controller (not one of the researchers) knows which group each patient belongs to, but the group members and the researchers do not. Some trials have more than two groups, as they may be examining the efficacy and safety of several drugs, for example, an "old" drug that has been used in practice for many years, and a "new" drug that has just reached clinical trials. Randomized, controlled, double-blind trials are the most frequently performed because they provide the most rigorous results.
- All clinical trials are strictly documented. Before starting a clinical trial, the objectives, goals, and methodology are described in the research protocol. The protocol is very important, because it is what doctors will check to understand and evaluate the results as well as how they will decide if a therapy or medicine is suitable for their own patients. This protocol must comply with the specific regulations of the country in which the experiment is carried out, and it must be approved by the regulatory authorities. In addition, there are protocols governing the handling of data obtained, biological waste, results, and so on.
- Clinical studies with people is always voluntary, and each participant signs documents confirming that they have received the necessary information to decide whether they want to participate. In some experiments whith humans, scientists may withhold from the participants some information about the experiment or its true purpose. When conducting a clinical trial, participants must know absolutely everything that will not affect the outcome of the experiment: they must be provided with all available information on safety, effects on the body, and so on. The only information that is hidden is which group this or that participant belongs to — placebo or experimental.
Conclusion
Clinical research is different from standard scientific experiments because it involves treating human patients with drugs under investigation. First, there is not only a control group, but also a comparison group, and these groups are randomized. Secondly, clinical trials are either blind or double-blind. Thirdly, all clinical trials are divided into several phases.