What are clinical trials?

Phase 1 examines the safety of the potential new treatment, often in just a few (5 – 20) people. In many cases, this phase involves healthy volunteers rather than patients. Participants are monitored for adverse reactions or side effects; if any appear that are judged too dangerous, the drug will not advance to further clinical trials phases.

Phase 2 determines the optimal dose size, timing of doses and drug delivery route (e.g., by mouth, or injection) for the next phase of testing. Although Phase 2 may provide some indication of the drug’s ability to treat the disease, the numbers of patients involved in this phase is too small for such findings to be relied upon.

Phase 3 aims to show whether the drug has a beneficial effect on patients. This stage of testing will usually involve hundreds of patients, which is enough to allow a reliable assessment of the drug’s efficacy. Phase 3 results will determine whether a drug is approved for use to treat a disease.

Phase 4 occurs after the drug has been approved for sale. With the drug in general use, further data can be gathered on its effects in an extremely large number of people over an extended period of time.

Traditional clinical trials are designed to test a single potential treatment against a placebo (dummy drug). This type of trial design can help to show whether a treatment is effective against the disease or not. However, setting up trials for each individual potential treatment can be costly, time-consuming and present logistical challenges.

Platform trials have been implemented in recent years to combat the expensive and time-consuming set up process. These types of trials are designed to last for years to come and have a multi-arm adaptive design. This means that:

• Multiple treatments can be tested at the same time
• Treatments can be removed quickly if found to have no benefit
• New treatments can be added throughout the trial
• A larger number of people are randomised onto a treatment than a placebo
• An increased number of people are eligible for the trial as strict criteria for participation is reduced

Current examples of MND platform trials running in the UK include MND-SMART and MAGNET.

In a well-designed Phase 2 or 3 clinical trial, half of the participants will be given placebo (‘dummy drug’) instead of the trial drug. This is to ensure that the beneficial effects observed in the trial are entirely down to the trial treatment itself and not due to the power of positive thinking, the extra attention from medical staff that comes with participating in a trial, or any other factor. 

Rigorous trials are 'double blinded'. This means that neither the doctors and nurses involved in the trial nor the trial participants know who is taking the real drug and who is taking the placebo. This prevents unintentional bias creeping in when participants are reporting how they feel or when the researchers are making assessments and looking at data.

Participants in trials should be assigned to the placebo group or treatment group at random. This is usually carried out by computer and prevents bias in choosing which patients get the trial drug.

The later stages of clinical testing, where the goal is to establish with certainty whether or not a treatment is of benefit, will generally involve hundreds of participants. Only by including this many people can researchers be sufficiently sure that the effects they are seeing are not occurring by chance.

The results of successful clinical trials will usually be shared with the research community through publication in reputable medical journals. Before the results can be published in these journals, the methods used in the trial will be scrutinised by independent scientists to ensure that they are reliable.