Background, phases, and types of clinical trials
Clinical trials play an indispensable role in the development and safe application of new drugs. These studies are conducted with human participants, allowing the effectiveness and safety of the preparations to be assessed under real-world conditions. The primary goal of clinical trials is to provide reliable data to medical professionals, supporting therapeutic decisions. Thorough testing ensures that only drugs meeting the highest quality standards are marketed. Thus, clinical trials are crucial for both patient safety and the availability of innovative therapies. Let’s understand what needs to be known about clinical trials, their types, and their phases!
Types of clinical trials
Clinical trials can be categorized in many ways, depending on the criteria considered. Below, we review the most important types that determine the structure and conduct of each trial.
Classification by type of control group
One key element of clinical trials is the presence and type of control group. The control group allows for a reliable assessment of the effectiveness and safety of the drug being studied.
In placebo-controlled trials, the control group receives a substance without the active ingredient. This "placebo" is indistinguishable in appearance from the drug being studied. The use of placebos raises ethical issues, which is why they are now mostly used only in the development of dietary supplements (such as vitamins).
In active-controlled trials, the control group receives an already registered drug used to treat the disease in question. This study design allows the effectiveness of the drug under development to be directly compared with the current standard therapy.
In single-arm trials, there is no control group; the condition of the treated patients is compared to baseline values. This type is generally used in the early stages of clinical development for preliminary assessment of effectiveness.
Three-arm trials are rarer but may include both placebo and active control groups along with the drug being studied. This design increases the reliability of the results but is more complex to conduct.
Classification by degree of blinding
The objectivity of clinical trial results is significantly influenced by the degree to which participants know the type of treatment they are receiving. Blinding reduces the impact of subjective factors.
In single-blind trials, the participants do not know whether they are receiving the study drug or the control treatment, but the study staff does know.
In double-blind trials, neither the participants nor the healthcare personnel conducting the study know who belongs to which group. This minimizes the likelihood of results being influenced by subjective expectations.
In open-label trials, both participants and researchers know which treatment is being administered. This type is only used in exceptional cases, mainly in the early phases of clinical development.
Grouping of participants
The reliability of a clinical trial also depends on how participants are assigned to different treatment groups. Improper grouping can distort the results.
In randomized trials, participants are assigned to groups randomly. This method ensures that the groups are similar at the start and that there are no differences that could affect the trial outcome.
In non-randomized trials, grouping is not random but based on other criteria, such as the order of enrollment. However, this carries the risk that there may be significant differences between the groups at the start, potentially distorting the results.
Timing of treatments
Clinical trials can also be categorized based on how different treatment groups follow each other over time.
In parallel design trials, treatments run simultaneously. Participants receive the same treatment they were assigned to at the beginning of the study throughout its duration.
Crossover trials consist of two periods. After the first phase, participants switch to the other treatment group following a "washout period," allowing each patient to receive both the investigational drug and the control at different times. The advantage of the crossover design is that patients act as their own controls, but it has several application conditions.
Phases of clinical development
Phase I - Assessment of tolerability and pharmacokinetics
The exploration of the effects of new drug candidates on the human body begins with Phase I clinical trials. These studies are conducted on carefully selected healthy volunteers under strict medical supervision.
In Phase I/a, the primary goal is to determine the safe starting dose. Participants receive gradually increasing single doses while continuously monitoring for potential side effects and the drug's behavior in the body.
In Phase I/b, multiple doses are administered to assess the drug's longer-term tolerability. The dosing duration can range from a few days to several weeks, with regular blood samples taken to monitor plasma concentration of the drug.
Phase II - Evaluation of efficacy and safety
In Phase II, the drug candidate is tested on patients to obtain initial indications of its therapeutic efficacy. These trials typically involve small, homogeneous patient groups.
In Phase II/a, open or single-arm designs are often used to quickly gather preliminary efficacy data. These results form the basis for planning later, more rigorously controlled studies.
In Phase II/b, trials are conducted under randomized, controlled conditions to reliably evaluate the drug candidate's effect. Dose optimization is also a critical aspect in this phase.
Phase III - Confirmatory studies on large patient populations
The goal of Phase III trials is to confirm the drug's efficacy and safety on large, diverse patient groups. These studies represent the entire patient population, thus revealing rarer side effects and drug interactions.
Phase IV - Post-marketing studies
Following drug approval, Phase IV studies continue in everyday use conditions. These post-marketing studies play an important role in monitoring the long-term safety of the product.
Phase IV provides the opportunity to detect very rare but potentially serious side effects since a much larger population uses the drug than in earlier trials. These studies contribute to fine-tuning the drug's use, optimizing dosing, and identifying the most suitable patient groups. Head-to-head comparisons with similar market drugs are often conducted to assess relative efficacy and safety.
Clinical trials play an essential role in bringing innovative drugs to market. Without them, it would be impossible to confirm the efficacy, safety, and tolerability of new products. Carefully planned clinical trials in various phases enable researchers to collect valuable data to determine whether a drug is suitable for market release.
A reliable partner like Inthera can be crucial for the successful execution of clinical trials. Inthera has decades of experience in the pharmaceutical industry and offers comprehensive services ranging from sourcing medicines for clinical trials to regulatory affairs and EU GMP services. Through an extensive partner network, they always procure reliable and high-quality products while ensuring the best market prices. Collaborating with Inthera provides access to a vast knowledge base and personalized guidance, ensuring market success.