MCDS-Therapy partner info: Mike Briggs
Clinical research relies on wonderful people to be successful. Whether it’s those doing the research, those managing it or those taking part in it, research cannot happen without the commitment, drive and collaborative efforts of fantastic people. Today, we would like to introduce you to one of the fantastic individuals working on MCDS-Therapy, our Coordinator Professor Mike Briggs.
Mike is a Professor of Skeletal Research at the University of Newcastle. More specifically, he is part of the Skeletal Research Group (SRG) at the Institute of Genetic Medicine (IGM), which is part of the Faculty of Medical Sciences (FMS). The IGM is home to around 50 Principal Investigators (the person who is responsible for the initiation and conduct of a research project) and their research teams. It has a strong focus on rare diseases, including rare musculoskeletal, cardiovascular, cancer and eye disorders. Mike’s main role is research, but he also teaches genetics on both undergraduate and postgraduate courses.
Mike has been heavily involved in genetic skeletal disease (GSD) research for over 30 years. His research has been integral to the identification of the genetic cause and disease mechanism behind a range of GSDs. His pre-clinical research means drugs that could potentially restore normal bone growth can now be identified and tested, as in the case of MCDS-Therapy. Mike has also been instrumental in establishing several European Consortia for the diagnosis of and research into rare skeletal diseases. These have included the European Skeletal Dysplasia Network, Eurogrow, SYBIL, and MCDS-Therapy itself.
MCDS-Therapy is an excellent example of the approach being taken to repurpose existing drugs for GSDs. Mike is the overall Coordinator of MCDS-Therapy, though he is also playing a scientific role in the identification and validation of potential RNA-based biomarkers (find out what biomarkers are and why we’re interested in them here).
At the weekend, you’ll most often find Mike trekking the fells of Northern England, watching the cricket, or doing some gardening.
To find out more about the University of Newcastle’s wider role in MCDS-Therapy, head over to our Partners webpage.
Health economics: what is it and why bother?
It may seem unusual that a team of mainly economists is involved in a clinical trial of a medical treatment. However, health economic methods offer invaluable insights into the cost-effectiveness of interventions for governments, individual governmental departments and individuals to make informed decisions on the value of healthcare.
The health economists involved in MCDS-Therapy have written this blog to tell you more about what they’re doing and why it is important.
Why do we need to think about health economics?
When we think about introducing new treatments, we need to consider whether any benefits that the new treatment provides are greater than its side-effects. We also need to think about whether or not the new treatment uses health care services in the best way possible. The reason for this is that health service resources are always limited and the decision to use them one way means we give up the opportunity to use them in other desirable ways. In addition, even when health services do not need to be directly paid for by the recipient of care, newer treatments may impose additional costs on recipients if they choose to use them. It is therefore imperative that the relative benefits, harms and costs are carefully considered. The additional costs of accessing health care may also be the added time and travel costs for recipients of new treatments – such as taking time off work to take their children to hospital for treatment.
In order to gain an understanding of the relative balance of benefits, harms and costs of a new treatment compared with current practice we can use health economic methods. Health economic methods provide the tools required to measure these costs in relation to health outcomes such as quality of life, and to ultimately allow us to understand if the new treatment intervention being evaluated is worthwhile.
What are we doing as part of this study?
As part of this study, we are carrying out a health economic analysis to understand the costs, benefits and harms of using a drug called carbamazepine for the treatment of metaphyseal chondrodysplasia, type Schmid (MCDS) and how it compares with currently available treatments. As there is no information currently available on the costs, benefits and harms of carbamazepine in patients with MCDS, a health economic analysis will be very useful for future decision-making about this treatment.
This health economic analysis involves two main parts:
- We will investigate whether the use of carbamazepine as a treatment for MCDS would be good value for money. To work this out, we will build a mathematical model that describes the potential impact that treatments for MCDS may have over the lifetime of a child. This model will be tailored to reflect the different way care is provided in three illustrative countries: the UK, Germany and Italy. If the use of carbamazepine is found to be value for money, then health services will be advised on what finances they need to put in place so that the treatment can be provided to everyone with MCDS in their respective countries. This will be done by completing what is called a budget impact analysis.
- We will use surveys to understand the preferences of patients with MCDS and their carers for the different outcomes of treatment (benefits versus harms), including how gains in one outcome might be traded off against reductions in another. For patients with MCDS, we will attempt to understand preferences around carbamazepine in terms of quality of care, effectiveness, harms and costs. For carers, we are interested in their preferences around caregiving situations involving carbamazepine treatment, which may be considered in terms of the intensity of the task, duration or availability of support.
Using established survey methods such as a discrete choice experiment (DCE), and best-worst scaling (BWS) we can find out what is the best way to provide care and how important successful treatment of MCDS is compared with the potential risks of the treatment. Both methods are standard practice in health economics and are incorporated into questionnaires given to patients. The first method, a DCE, involves answering a series of questions which ask you to make a choice between two options for the way care may be provided. The second method, a BWS, requires the reader to choose the best or worst option to a question on the survey. By examining the responses to both these methods, we can better understand the preferences of patients with MCDS and their carers for treatment outcomes.
What have we done so far?
Over the first year of the study, our focus has been on understanding the treatments for MCDS that are currently available and the clinical pathways of care that children with MCDS currently follow. These pathways of care will form the basis for the mathematical model that will be used to estimate the value for money of carbamazepine, and for the budget impact analysis. Given the limited information available on this rare condition, by speaking to the clinicians involved in the study we were able to gain an understanding of how people with MCDS are currently diagnosed and treated. We were also able to consider what happens to someone with MCDS over time, including the different treatments that might be used, and the complications (harms) that may be experienced.
Using the information we have gained from clinicians, we developed what is called a conceptual model of care – this is really just a diagram of how care is provided and what might happen over the lifetime of someone with MCDS. This conceptual model was also presented to German- and Italian-based clinicians to get their advice about whether this conceptual model reflects the way care is provided for people with MCDS in their respective countries. By doing this we can understand how the mathematical model might need to be changed to reflect the way care is provided in each country.
We have also made further progress on our study of the preferences of patients and their carers by collating a large body of literature on DCE and BWS studies. We are using this literature to help us design the survey presented to patients, carers and clinicians to elicit their preferences on the benefits, harms and costs of carbamazepine.
What are we going to do next?
Over the coming year, the focus of the health economics team will be on adapting our conceptual models of care into fully-functioning mathematical models and developing the survey of the study of the preferences of patients and carers. To do this we will need to get information from a variety of sources, such as expert opinion, the clinical study, and previous research. Although this previous research is very limited, a health economics intern at Newcastle University spent some weeks in the summer of 2018 attempting to identify any papers (clinical or economic) in related disease areas. We will use these as a source of additional information to inform the economic analysis. However, a vital part of helping to complete this research will be by speaking to people with MCDS and their carers.
What does a CTU do?
Academics and researchers are absolutely fantastic when it comes to science. But when it comes to running clinical trials and all the regulations surrounding them, they need a little bit of help moving forward. That’s where a Clinical Trials Unit, or CTU, comes in.
Connecting with other organisations
MCDS is a rare genetic skeletal disease. There are plenty of organisations and networks around the world who patients, families and doctors can get information and support from. There are no other organisations focused on MCDS but the list below features many which are specific to skeletal dysplasia or rare diseases.
International
- Little People of the World: https://www.littlepeopleoftheworld.org/
- Rare Diseases International: https://www.rarediseasesinternational.org/
Europe
- European Skeletal Dysplasia Network: http://www.esdn.org/eug/
- ERN-BOND – European Reference Network on Rare Bone Diseases: http://ernbond.eu/
- EURORDIS – Rare Diseases Europe: https://www.eurordis.org/
UK
- Little People UK: https://littlepeopleuk.org/
- Restricted Growth Association: https://rgauk.org/
- Dwarf Sports Association UK: https://www.dsauk.org/
- Little People of Ireland: http://www.lpi.ie/
- Genetic Alliance UK: https://www.geneticalliance.org.uk/
- Rare Diseases UK: https://www.raredisease.org.uk/
- Genetic Disorders UK: https://www.geneticdisordersuk.org/
- Rare Diseases Ireland: http://rdi.ie/
Australia
- Genetic Alliance Australia: http://www.geneticalliance.org.au/
- SSPA – Short Statured People of Australia: https://sspa.org.au/
- Rare Voices Australia: http://www.rarevoices.org.au/
Belgium
- RaDiOrg Belgium – Rare Disease Organisation Belgium: http://www.radiorg.be/
France
- APPT – Association des Personnes de Petite Taille: https://appt.asso.fr/
- Alliance Maladies Rares: https://www.alliance-maladies-rares.org/
Germany
- VKM ‐ BundesselbsthilfeVerband Kleinwüchsiger Menschen: https://www.kleinwuchs.de/
- BKMF – Bundesverband Kleinwüchsige Menschen und ihre Familien: https://www.bkmf.de/
- BSHV – Bundesselbsthilfevereinigung für Kinder, Jugendliche und Erwachsene mit seltenen, chronischen Skelett-Erkrankungen: https://www.bshv-seltene-skelett-erkrankungen.com/
- ACHSE – Allianz Chronischer Seltener Erkrankungen: https://www.achse-online.de/de/
Italy
- AISAC – Associazione per l’Informazione e lo Studio dell’Acondroplasia: https://www.aisac.it/
- UNIAMO – Federazione Italiana Malattie Rare: http://www.uniamo.org/
Why are we doing biomarker discovery?
What is a biomarker and why is the MCDS-Therapy team trying to find one? Sciomics, the partner focusing on this part of our work, have written this handy blog to keep you in-the-know.
Having a rare disease is challenging for patients and their loved ones as the diagnosis is often delayed or inaccurate, specialists are scarce and even upon being successfully diagnosed a treatment may not be readily available.
The whole Sciomics team is very grateful to be part of the MCDS Therapy project having the aim of repurposing a safe and proven drug to treat Metaphyseal Chondrodysplasia, Type Schmid (MCDS). Important questions are still to be answered, does the drug work in every child, do the children respond quickly or are there adverse events to be expected?
How can we try to answer these questions? We need biomarker. A biomarker is something we can measure in order to be able to say the drug works or does not. An unrelated example for a biomarker is measuring your temperature if you have a cold. Is it elevated you are likely to be sick or if it is normal you are probably not. Here at Sciomics we measure more than 1000 proteins from a blood sample to identify different proteins as biomarkers potentially being able to judge whether the new therapy is working or has only little to no positive effect.
This is especially important for MCDS as the only biomarker so far is growth rate which can be very slow for natural reasons during a certain period of time or caused by the disease. Children need to be monitored for years until it can be concluded whether the drug has an effect or not. Having a simple biomarker test which can indicate a response to the drug quickly, maybe even after a few weeks, using an easily obtainable blood sample would be of great value to the children and their parents.
We at Sciomics can investigate proteins in tiny blood samples in order to find such biomarkers. For current diagnostic measurements 10ml of blood are taken to look at a handful of parameters some of them already being proteins. Our technology can measure more than 1000 proteins using a thousand times less blood while giving us a hundred times more information.
Looking at very small blood samples has many advantages, the sample is almost pain-free to obtain, every patient can give a tiny amount of blood even sick children and it minimises the children’s risk to suffer from any negative events due to the test. In order to be able to look at 1000 and more proteins, usually your Doctor only looks at 5-10 proteins, we had to invent and develop a whole new method. This was done over more than 15 years of research and out of the 12 people working at Sciomics many are scientists.
We hope that our research within the MCDS Therapy consortium will have a positive impact on many children’s and their family’s lives.
