Clinical trials
Clinical trials are a crucial stage of drug development. They are designed to test whether a drug or drug combination is safe, effective and works well in the intended patient population. In most countries, no new medicine can reach the market without being clinically tested and proven in humans first.
There are typically three different phases of clinical trials, termed Phase I, II and III. In most cases each phase builds on the results of the phase before i.e. the information collected during the course of a trial will determine whether the new drug can proceed to the next phase.
If the drug successfully passes through Phases I, II and III, it will usually be approved by the appropriate licensing authority and become available for use.
Phase I trials typically involve previously untested new drugs or new drug combinations. They are not designed to determine whether a new drug or new drug combination works but to determine the best dose, schedule and safety profile.
If successful, they lead to Phase II studies which address whether the new drug/combination is effective using the optimum dose and schedule derived from the Phase I trial. Provided a certain proportion of patients benefit and the safety profile is acceptable, then the new treatment progresses to Phase III.
Phase III (and some larger phase II) studies are used to compare one treatment with another. Typically, the new drug/combination is compared with the current standard treatment to assess whether it provides additional benefit. This comparison depends on randomisation whereby the treatment patients receive is allocated by means of a computer. This is done to help avoid bias towards one treatment and to ensure an equal mix of patients with different characteristics such as age, sex and states of health in each group.
More information on the different phases of clinical trials are summarised in Table 2:
Table 2: Clinical trial phases
| Phase I | |
|---|---|
| Designed to | Determine the pharmacokinetics (absorption, metabolism and elimination) and pharmacodynamics (effects on the body) of the drug in humans Identify the maximum tolerated dose (MTD) Establish a safe, therapeutic dose and dosing schedule Identify side effects |
| Numbers tested | Usually between 15 – 50 participants |
| Participants | Generally, healthy volunteers for non-cancer drugs In cancer trials, patients with end-stage disease and/or who haven’t responded to standard treatments or lack other treatment options |
| Benefits | Opportunity for patients to receive a new treatment that might prove effective against a disease. May be the only way of accessing novel, developmental drug |
| Phase II | |
|---|---|
| Designed to | Test how well the drug works (efficacy) Further assess safety and side effects in larger group (toxicity) |
| Numbers tested | Larger groups: 100 – 500 participants |
| Participants | Patients with advanced disease |
| Benefits | Opportunity for patients to receive a new treatment that might prove effective against a disease. May be the only way of accessing novel, developmental drug |
| Phase III | |
|---|---|
| Designed to | Compare new treatment against standard treatment(s) for effectiveness in randomised patients (i.e. assess how well the treatment works under true circumstances in comparison with current ‘gold standard’ treatment) |
| Numbers tested | 300 – 3,000 (normally multi-centre) participants Usually less than 1,000 participants for myeloma |
| Participants | Patients for whom the treatment is designed |
| Benefits | Opportunity for patients to receive a new treatment that might prove effective against a disease. May be the only way of accessing novel, developmental drug Can provide patients with an effective drug while regulatory submission is still pending |
All trials, regardless of the phase, are run according to a strict plan or protocol. Each protocol must be inspected and approved beforehand by various regulatory bodies, including an ethics committee, to protect the rights, dignity and safety of participants taking part.
The protocol states the aims of the trial and what outcome measurements are to be used to determine the efficacy of the treatment. It also defines the eligibility criteria and outlines the schedule of tests, procedures, treatments, dosages and length of the study.
Every trial will have its own specific eligibility criteria depending on the aim of the trial and the research questions being asked but typically focus on whether the myeloma is newly diagnosed, relapsed or refractory to treatment, any prior treatments and additional co-morbidities. The criteria are there to protect the safety of patients and ensure they are not exposed to unnecessary risk. Those who do not fit the criteria will not be able to participate in that trial.
Broadly speaking, the clinical trial stage of drug development can take up to ten years to complete. Similar to preclinical testing, the attrition rate, even at this stage, remains high and many new drugs do not successfully complete all phases of clinical trial.
There is also wide agreement that one of several reasons for the length of time in producing new treatments continues to be problems in recruiting patients. Insufficient numbers of participants for a trial leads to delays in the development of new and innovative treatment options and ultimately patients lose out.
Nurses have a key role in making a difference to the way in which patients are recruited to clinical trials. They should ensure patients are aware of opportunities to take part in clinical trials and clearly understand the purpose and goals of these trials. Nurses should be knowledgeable about clinical trials in general and be fully aware of the available trials in the local area so that they can inform patients about each trial they are eligible to participate in. Information on clinical trials can be found on reliable websites such as https://www.clinicaltrials.gov/ and the Myeloma Trial Finder. Nurses should also be a safe space for patients to discuss their concerns about taking part in a clinical trial, and particularly for older or more frail patients at late stages of treatment, provide an opportunity for them to be honest about whether they would like to go down this route.