You may think that MPN research is primarily focused on investigating new drugs for better blood control in essential thrombocythaemia (ET), myelofibrosis (MF) or polycythaemia vera (PV) and ones that offer patients a longer and better quality of life, indeed eventually hopefully a cure. However there are also a number of projects researching why patients get MPNs and also the science behind the diseases, for example the discovery of the JAK2 and calreticulin and other mutations.
Clinical trials supply doctors and healthcare professionals with evidence about what treatments actually benefit patients. Trials look at the safety, possible side effects and the benefit of newer drugs against established ones. All trials have to follow specific medical protocols which are designed to protect patient safety and provide meaningful results. All trials offered to patients will have been through several approval phases beforehand, in particular approval from an independent research ethics committee which will review safety and monitoring as well as whether the study is considered to be needed. The committee protects the rights and interests of patients who enter trials.
Trials In the NHS trials are funded in a variety of ways which include: the National Institute for Health Research, (NIHR), the Medical Research Council, (MRC), the Department of Health and other government departments, medical research charities and pharmaceutical and other healthcare representatives.
When research is published, the method of funding will be declared and when a patient is asked to take part in trials, they should be told how it is being funded. For MPN patients some funding for trials has been donated by MPN Voice – e.g. the vorinostat, MOSAICC and MEASURES studies.
Different trial phases
Clinical trials using new medicines are normally classified into four phases.
Phase one trials
These are early trials in the development of new medicines, primarily concerned with safety and where drugs are given to only a small number of subjects, sometimes these are healthy volunteers and sometimes they are patients with the disease. To minimise the risk, dosage levels are small at the start of the trial and increased if minor or no side effects are demonstrated.
Phase two trials
These are performed on a larger number of patients with specific diseases to evaluate the side effects and benefits for the condition, a clear dose range for the drug is identified. Some phase two studies may be randomised; i.e. a computer decides what treatment a patient gets, and compares the new treatment to another existing treatment or placebo (dummy pill).
Phase three trials
These are for medicines that have passed phases one and two. Larger numbers of participants are included at this stage and new drugs are compared with existing treatments or placebo. Results will consider side effects and outcomes. Most of these studies are randomised. Depending on the design of the research, patients not on the trial drug may sometimes cross over to receive the trial drug.
Phase four trials
Once new medicines have successfully passed through the first 3 stages, the medicine will then be given a marketing licence, which means that the drug is available on prescription. Ongoing monitoring will occur on safety, side effects and long- term risks and benefits, such ongoing monitoring is usually the job of a phase four study, these are often very large and are not randomised.
Questions to ask
If you are asked to consider being part of a trial, or want to investigate trials that are available, it is sensible to consider a number of issues:
- Why is the trial running?
- What are the questions being asked?
- How is it expected to help me or other MPN patients?
- How long is the trial planned to run for?
- How much time would be needed to attend for appointments and what frequency?
- Will I need to take time off work?
- What extra tests/appointments might be required?
- Will the cost of travel to take part in the trial be covered?
- Where will I get the drugs? Hospital/GP or by post?
- Who needs to be contacted if there are any questions or problems?
- What happens if I want to stop the trial before the end of the research period?
- Is there any potential impact on future treatment options?
- What are the potential side effects –physical and/or emotional?
- What paperwork will I have to do – questionnaires/diary etc?
- How long will it be before the trial results are published and how do I find out the results?
- How is the trial funded?
Patients who are asked to take part in a trial have free will to say yes or no. The doctor organising the trial should discuss why you should consider being involved and the potential risks and benefits. In particular, before deciding, you will be offered a patient information leaflet, this contains information about why the study is being done, what is already known, what the potential side effects are, how frequent your visits would be and who to contact for more information.
There are many new drug trials planned or running for MPN patients and your haematologist will be keeping abreast of these opportunities to best manage your condition.
However, unfortunately sometimes it is not possible for MPN patients to take part in trials when they do not fulfil the specific eligibility criteria: e.g. age or physical fitness or other medical conditions may make a patient less suitable for a drugs trial. These issues will all be discussed at the time of considering trials and ongoing treatment options and may be tested for in the so-called screening phase of the trial before treatment is begun.