What is research and why is it important?

In the broadest sense of the word, the definition of research includes any gathering of information and facts for the advancement of knowledge.  Although knowledge about JIA is increasing and treatments have improved, there are many questions that remain unanswered. Research is key to reducing the impact of JIA, and strives to allow children and young people with JIA to have a normal future.

SNAC believes it is important for families to have information about research and to have an appreciation of its value for the advancement of knowledge leading to the hope of better outcomes and treatments for children with JIA in the future. We also believe SNAC has a role, through collaboration with the paediatric rheumatology community, to help to shape research priorities and work with the mutual aim of high quality relevant research for children with JIA.

What does research involve?

There are many different types of research studies. Each type helps contribute to the understanding of the condition. Research may be laboratory or clinical (involve patients) or both. Examples include:

Epidemiological studies

– explore patterns, causes and effect of conditions. For example:

  • studies which try to understand exposure factors (behavioural, environmental or clinical factors that could potentially influence the disease) and investigates whether there is an effect of exposure on outcome.
  • studies which examine how frequently a condition occurs in childhood in a defined population.
  • a cohort study will involve following a large group of individuals with the condition, often in a defined population, over a period of time, to try and establish the long term effects of a condition.

Diagnostic studies

– are conducted to find better tests or procedures for diagnosing a particular disease or condition.

Quality of Life studies

– explore ways to improve comfort, function and quality of life, particularly for those with chronic conditions.

For example a study might look at how JIA can affect your child’s ability to exercise.

Experimental treatment studies or clinical trials

– A clinical trial is a medical research study involving people. There are many different types of clinical trials. For example, a trial may compare one treatment against another, or a new drug against a dummy (or placebo) to try and show that it is effective. Most clinical trials involve patients but sometimes also healthy volunteers.

– A clinical trial may be observational (where researchers observe patients and measure outcomes) or interventional (where researchers give patients a particular treatment or intervention).

– Not everyone in a trial gets the same treatment. Some trials are known as randomised trials. Patients are randomly assigned, usually by a computer, to different ‘arms’ of the trial (different treatments. This method means than neither the patient/parent or their doctor will be able to influence which treatment arm the patient is in, and therefore helps ensure that treatment is not biased. Normally equal numbers of patients are in each and at the end of the trial the results are compared.

– The safety of patients in trials is really important. All trial protocols are reviewed and approved by ethics and regulatory committees. All the possible risks and benefits of taking part will be explained to you.

All studies of any sort happening in the health service have to be approved by an ethics committee who looks at whether the study is properly designed, whether it will give worthwhile results and whether the team running it are qualified to do so. Each hospital entering anyone in a study will have to apply for approval for the study to happen. You can therefore feel confident that any research you are invited to be involved in is ethical, worthwhile and safe for your child.

Why are clinical trials important in Paediatric Rheumatology?

We need clinical trials to help us continue to improve our treatment of JIA and therefore quality of life and outcome for families affected by this group of conditions. Clinical trials allow the testing of new treatments and ways of controlling symptoms or investigate new ways of preventing complications.

The need for clinical trials in children has been increasingly recognised by the scientific community and broader public, leading to new laws both in the EU and USA. It is now compulsory for new drugs to be tested in children as well as adults before they are licensed for use.

Are there different types of clinical trials?

Yes

– there are 4 phases to a clinical trial. The aim of each phase allows us to find something different about the new treatments or procedure.

Phase 1 – tests new treatments on people for the first time. This helps identify the correct dose of new drugs and any possible side effects. These trials are carried out in only a small number of patients.

Phase 2 – tests whether a treatment is likely to be effective at the dose(s) chosen. They aim to find out how well the new treatment works for particular conditions and to define any unwanted adverse effects. Again these trials use relatively small number of patients.

Phase 3 – confirms the benefit of treatment, often compared with the current or ‘standard’ treatment. These trials involve larger numbers of patients in real clinical care settings and usually run for much longer than phase 1 or 2 trials. They may run across different countries at the same time.

Phase 4 – Once the treatment has been approved, post marketing studies continue to ensure risks, benefits and optimal use. These are studies which collect further information about problems or benefits of a drug after it is in widespread use in a real-life situation.

Can my child be entered into a trial?

The British Paediatric and Adolescent Rheumatology Society (BSPAR) Standards of Care for JIA state that every child with JIA should be given the opportunity to be enrolled in a clinical trial or well conducted study from point of diagnosis onwards. They should have the option of contributing towards genetic studies for subsequent investigation into the cause of their condition.

Although this goal has not yet been achieved for every child with JIA, work is being done to try and help achieve this.

The NIHR Medicine for Children Research Network (MCRN) was established in 2005 to improve to coordination, speed and quality of randomised controlled trials and other well designed studies of medicines for children and adolescents, including those for prevention, diagnosis and treatment.

The Scottish Paediatric and Adolescent Rheumatology Network (SPARN) is working closely with Scottish Medicine for Children Research Clinical Network to help facilitate opportunities for children in Scotland to have access to clinical trials.

There are very clear guidelines about which patients are eligible for any study or trial. The rules for being included are clearly set out in the trial protocol. It is important that the patient is an exact match to these criteria and that patient or parents agree to take part. Taking part in a study is entirely voluntary.

If there is a trial suitable for your child and it is running in the hospital that your child attends then your paediatric rheumatology team will approach you and your child. Detailed information sheets are provided for parents and children of various ages and there will be opportunities to discuss the trial with doctors and nurses and to ask any questions.

If you agree to take part in a trial, you can change your mind at any time. Your doctor will respect that decision & your child will still receive the best known and proven treatment.

What research projects are currently on going in Scotland?

  1. Childhood Arthritis Prospective Study (Glasgow and Edinburgh)
    The aim of this programme of work is to identify the predictors of outcome, both short- and long-term, following presentation with childhood onset inflammatory arthritis and to identify the relative contributions of socio-demographic, clinical, psychological, laboratory and genetic factors and treatment in explaining outcome.

CAPS

  1. The Study of Biologic Use in UK Children with Rheumatic Diseases (Glasgow, Edinburgh, Aberdeen, Ayrshire and Tayside currently)
    This aim of this study is to look at the long term safety and efficacy of biologic therapies in children with rheumatic disease. A parallel cohort of children starting Methotrexate will also be collected. All children will be followed for a minimum of 5 years.

Biologics for children with rheumatic diseases

  1. BSPAR Etanercept Cohort Study (Glasgow and Edinburgh)
    The BSPAR Etanercept Cohort study (previously known as BSPAR ­­­Etanercept registry) collects detailed information on the effectiveness and safety of Etanercept in children with JIA. A parallel group of children with JIA treated with Methotrexate is also being recruited in order to compare side effects and long term outcomes between the two treatment groups.
  1. SYCAMORE Study (Recruitment has started in Edinburgh and Glasgow has approval)
    The aim of this study is to look at the safety, cost and clinical effectiveness of Adalimumab combined with methotrexate for the treatment of JIA associated Uveitis.

Sycamoretrial.org.uk

  1. JIA Genetics Consortium UK (Edinburgh and Aberdeen)
    National blood and genetic material collection for studies of arthritis and rheumatic diseases.
  1. A pilot study to investigate the microbiota profile and metabolic activity in the colon of juvenile idiopathic arthritis patients at risk of developing Crohn’s disease (Glasgow)
  1. Educational Research Project – about the education of doctors working in Clinical Networks in Paediatric Rheumatology 
(various SPARN centres and other networks in UK)
    The aim is to identify the learning needs of doctors involved in delivering the best possible care for children and young people with juvenile idiopathic arthritis within a clinical network.

Example of recent research publications that Scotland has contributed to:

Foot orthoses in children with juvenile idiopathic arthritis: a randomised controlled trial

Arch Dis Child doi:10.1136/archdischild-2013-305166 Andrea Coda1, Peter W Fowlie2, Joyce E Davidson3, Jo Walsh4, Tom Carline5, Derek Santos5

There is limited evidence supporting the podiatric treatment of children with juvenile idiopathic arthritis (JIA). This multicentre randomised controlled trial aimed to determine whether preformed foot orthoses  mpacted on pain and quality of life in children with JIA. This study recruited 60 children from Dundee and Edinburgh. Conclusions: Fitted foot orthoses may reduce pain and improve quality of life in selected children with JIA.

Examples of other research projects for JIA currently recruiting patients around the UK/Europe

  1. MCRN027
    A multicenter, randomized, double-blind, placebo controlled efficacy and safety trial of intravenous zoledronic acid twice yearly compared to placebo in osteoporotic children treated with glucocorticoids for chronic inflammatory conditions.
  1. MCRN069
    An open-label extension study of canakinumab (ACZ885) in patients with Systemic Juvenile Idiopathic Arthritis (SJIA) and active systemic manifestations.
  1. SPARKS CHARMS
    A study of the immunological and genetic mechanisms of response and psychological response to, standard disease management in JIA.

UK Clinical Research Network Study Portfolio

  1. JIGSAW (WA28118)
    An open-label multicentre study investigating the pharmacokinetics, pharmacodynamics and safety of tocilizumab following subcutaneous administration in patients with active Systemic onset Juvenile Idiopathic Arthritis.
  1. JIGSAW (WA28117)
    An open-label multicentre study investigating the pharmacokinetics, pharmacodynamics and safety of tocilizumab following subcutaneous administration in patients with active polyarticular course JIA.

How can families get involved in research priorities?

High quality research, recruitment and outcomes depend on listening to voices of children and young people, as well as their families and careers. It is important to take into account their experiences, priorities and perspectives.

The SNAC family weekend away is a great opportunity to hear your thoughts. Sharon Douglas is a Parent representative/Consumer on the NIHR Clinical Research Network: Paediatric rheumatology CSG.
If you have any suggestions and what you feel are important. Then email sharondouglas©snac.uk.com

The James Lind Alliance (JLA) is a non-profit making initiative which was established in 2004, which brings patients, carers and clinicians together to identify and prioritise the top 10 uncertainties, or ‘unanswered questions’, about the effects of treatments that they agree are most important.

http://www.lindalliance.org

http://www.cso.scot.nhs.uk

http://www.invo.org.uk

The above websites may be of interest for further information about patient involvement and research.