The types of clinical trials by stage of development, or phase, are well known, but in this review we will discuss different types of clinical trials based on their design.
Randomized vs Non-randomized clinical trials
While randomized trials, where the treatment is allocated on a random principle, are the most common ones there are also non-randomized efficacy trials. The Non-randomized trials allocate all patients to the same treatment and usually their results are compared with results of historical treatment with similar therapy. Such comparison would be biased in many ways and this is one of the reasons why that type of clinical trials is avoided. However sometimes there are ethical considerations that require non-randomized clinical trials – for example, when the study involves patients who require heart, kidney or liver transplant they cannot be excluded from life-saving procedure for the purpose of the study and should be offer the same treatment.
What types of phase 3 randomized trials do we have?
The randomized controlled trials are the standard against which other trial designs may be compared.
- Equipoise and Uncertainty
This type of clinical trial compare two parallel treatments and its aim is to identify which treatment is best for the patient. There are two main aspects in that type of studies: all patients must have the medical condition and meet all requirements and both treatment options must be appropriate for these patients. For example, a study for patients with infection, which require antibiotics are offered to participate in a clinical trial that compares 2 antibiotics, both suitable for treatment of the infection. Patients are randomly allocated treatment after they are consented and enrolled in the study.
- More than 2 groups
There are cases where there are more than 2 parallel groups that are compared. However this could make the data analysis quite challenging. Example for such trial would be patients with breast cancer who receive different combinations of chemotherapy medications.
- Factorial Designs
In this case there are 2 groups with parallel treatment. Factorial design allows not only to compare treatments but also to study possible drug interactions. For example, patients with dyslipidaemia are enrolled in a study where they are randomly allocated either placebo, atorovastin alone, fish oil alone or atorovastin and fish oil.
- Equivalence Trials
Equivalence trials are similar to parallel trials with that difference that they try to compare treatments, which are similar or “at least as good as” the standard of care. The analysis of such trials is quite complex.
- Standard or Control Therapy
This is the case where the clinical trial compares new therapy with standard or care or “no treatment”. The purpose of such set up is to determine if the new therapy is superior to standard of care or more beneficial to patients in comparison to “no treatment”. For example, patients with breast cancer who have had surgery may receive chemotherapy after surgery (adjuvant treatment) in comparison to patients who will not receive chemotherapy (“no treatment”). In some cases patients from control group may receive placebo. The purpose of using placebo is to avoid bias when comparing two different treatment options.
- Large Simple Trials
In the fields of oncology and cardiovascular diseases it is common to establish large simple studies. This is often done in phase 4 when the medications are already on the market and their side effects are well studied and minimal. For example, this could be a clinical trial to establish the benefits of taking aspirin to prevent cardiovascular diseases.
- Intervention and Prevention Trials
Example of intervention trial would be encouraging “safe sex” to prevent HIV spread or breast cancer screening trials for early detection of cancer. In such cases due to risk of contamination or logistics the studies could facilitate randomization of whole communities instead of individual patients.
- Crossover Trials
The design of these trials is different from parallel studies because it allows patients to be enrolled on active treatment and placebo and later on after a wash out phase they could be switched (these who received placebo will be allocated active treatment and vice versa). This option allows more patients to obtain the study drug however it will be possible only for medical conditions where treatment could be withheld for some period of time.
- Sequential Trials
Because often phase 3 studies are running over extended period of time sequential trial design allows the study to be closed earlier if sufficient safety data is collected or establish if one of the treatment options is superior and extend the study on the efficient treatment only.
- Zelen’s Design
Zelen’s design is related to informed consent option. It is more of a special case for clinicians who would like to include in clinical trials patients who are not willing to go on study drug. For example, patients with breast cancer who are not willing to start experimental treatment are offered standard of care treatment and they don’t need to be consented. However this type of design is generally avoided.
Selection of best design for the clinical trial depends on the disease, expected outcome, patient population and many more factors which contribute to be selection.
Source: Textbook of Clinical Trials
Author: Olga Peycheva
Olga is a clinical research professional who has been working in clinical research since 2005. She has extensive experience in clinical research in Eastern and Western Europe.
Originally published on 2 Nov 2016