Who are you and what is your relationship to OI?

I am Dagmar Mekking from the Netherlands. I am a mother of a 15 year old daughter with OI. Also I am the director of Foundation Care4BrittleBones. The purpose of the foundation is to improve quality of life for people with OI through research.

What was the background for Key4OI in the first phase? 

You may have heard the sentence “What gets measured, gets done” or “You can’t really improve anything, unless you measure it”. Businesses are all using these concepts to drive business performance. In the last 10 years, healthcare around the world started to go into this direction too. It turned out that the focus of healthcare measures was mostly on “process”, as in “how often does someone receive physiotherapy” or “how often does someone get medication X and how much”. This was easy to measure, it was important for safety, for healthcare insurance and for the billing system.

Across healthcare (not just OI) it turned out that relatively little attention went to the outcomes in the person that was treated. We knew what treatment was administered, but if it actually worked was often not known. The key is really to consider what the value is that a patient gets from undergoing any kind of treatment. Foundation Care4BrittleBones has picked up this general trend and coordinated the development and implementation of this “idea” for the OI community.

Why was there a need for this project?

OI is complex and everyone is different. There are potentially > 100 of things we could be measuring. Did you know that each year about 200 articles are being published about OI? There is a lot of dedicated people out there and that’s absolutely amazing! We would like to argue though that the activity levels and the “local insights” somehow don’t translate into improvements for everyone with OI. We believe we can do better in sharing knowledge and doing research together to really improve quality of life. For any rare disease we see that it is critical to determine the most important topics to focus on and then to “organise” ourselves to make progress in this area. This is what Key4OI can do.

So what is an outcome measure?

Traditionally healthcare measures focused on process measures. Key4OI focuses on outcome measures. They measure the result in people with OI, regardless of the treatment. If we all measure the same areas (for example: fractures, pain, fatigue, mobility, emotional wellbeing etc) and we measure with the same measuring stick, this will open up a world of new insights about OI and which interventions are effective for which patients (for instance for which types of OI). In Key4OI we focus on CROMS and PROMS.

Clinically reported outcome measures (CROMS) are measures that a hospital/doctor will need to generate. Examples: a DEXA scan, an X-Ray, a Lung function test etc. Patient reported outcome measures (PROMS) are measures reported by the person with OI. Examples: the level of pain or fatigue, the ability to participate in society or emotional wellbeing. The last 10 years it has become widely accepted that the perception of the patient is probably what matters most. We have to know how the people with the condition experience quality of life.

Which methods were used in Key4OI and who were engaged in the project? 

First we engaged with the patient organisations that have a big international footprint, OIFE and OIF and made sure they supported the project. Both were in the steering committee that oversaw the project of developing Key4OI 2018-2019. We formed a project lead team which consisted of 5 healthcare providers in the Netherlands and Care4BrittleBones. The decisions were all taken by an expert team of 25 people of which 20% had OI themselves.

Can you explain the different steps in the process?

1. Determine vision

We determined our vision to develop an outcome set as “broad as life”, useful for routine clinical care of any multidisciplinary team and beneficial for every person with OI.

2. Convene the project and expert team

It was critical to have the right mix of expertise in this group: geographically diverse, experienced in children and in adults with OI and multidisciplinary and with strong representation of the OI community  (ca 20% of the group were experts with OI). We consulted a lot with OIFE and OIF to have experts involved that really understand OI and that we as a community trust a lot.

3. Literature search

The project team dived into the literature and clinical trials to understand the topic of outcome measures of OI “today”. We had great help from the specialised NGO ICHOM (International Consortium of Health Outcome Measures) and a professor for epidemiology and outcome measurements, Prof. C. Terwee, who advised us.

4. Methodology

We then determined the methodology to develop a formal agreement on a set of outcome measures for OI (so called “consensus”), selecting the ICHOM standard due to its strong international reputation. ICHOM is an NGO which has developed a strong scientific approach how to investigate a condition with regard to the impact it has on the individual patient (eg lung cancer, depression, arthritis) leveraging the voices of patients and experts. They are also providing a structured process on how to prioritize the findings using the ICF framework and measure the outcomes in the identified priority areas in a scientifically strong (“validated”) way. They provide a quality control for any ICHOM accredited set. We are proud that Key4OI has achieved the accreditation in 2021.

5. Focus groups to determine domains

Domains can be translated to “topics” or “areas”.  The method behind it is based on the International Framework for Functional outcomes (“ICF – framework”). The framework applies worldwide and is also used by the World Health Organisation (WHO). It describes all the “domains”/ “topics” we need to think about for “any humans”. This way we made sure we didn’t forget anything. Each domain is described in a precise scientific way that is understood in the same way in every country. The choice of domains was done by the Expert team and based on input from focus groups of people with OI and many discussions withing the Expert team. We looked for countries willing to organise focus groups for adolescents and adults. We translated the material and helped to prepare their local facilitators. The discussions were held in local languages, recorded, transcribed and translated by a scientific translation service provider for the medical sector.

6. Find the best possible, validated measures

Once the domains were selected and we knew what was relevant per domain, we worked within the team to find the best possible, validated measures to capture what was going on in this area. We collected “all possible measuring tools” available for the topic and made sure we understood them in detail (eg some are only for certain age groups or have costs attached etc).  We then made the best possible content validated match between the list of validated measures and what the OI community and experts were looking for.

We used a Delphi process to take decisions within the Expert group. A Delphi process is a scientific anonymous survey which is used to finalise a discussion and ensure that a consensus has been achieved without any kind of pressure.  This is important to make sure the decision is objective, clear and unbiased by “who said what”. For example, we used Delphi to determine which domains would be measured in Key4OI and which areas not. We also used it to determine the measurement tool that is most appropriate to use based on the input we have for this domain.

7. Summary, recommendation and scientific article

We bundled it all together to ensure it covered all aspects and no overlaps and described this in a way that every hospital is theoretically able to work with it. This summary was then published in the OrphaNet Journal of Rare Diseases.

Were there any surprises along the way?

Many! Let me mention one:  We discussed thoroughly if we should include pulmonary function into Key4OI. At the time the experts felt this topic was primarily relevant for people with a severe form of OI and not for all people with OI. Thanks to the great work of the OI Foundation in particular, the thinking has turned around and we are now discussing to include it into Key4OI after all. The Key4OI set is as “smart” or “not smart” as the state of our scientific insight.

Why did you establish Key4OIPlus?   

Key4OIPlus was developed since the three areas (cardiopulmonary, dental and ENT) were not covered in Key4OI. There was a lot of feedback that these 3 areas are of very high importance for quality of life for (at least) some people with OI. There were enough experts and people with OI interested in bottoming these topics out with a separate small outcome set that could be added to the base set whenever needed. Two of the three areas may end up in Key4OI after all, as the working group has been able to make a strong case for this. But this discussion is still ongoing. We have used the exact same method as for Key4OI.

What is the role of the pilots?

We established pilots because we knew there was a lot of “teething problems” to deal with to be able to implement Key4OI in routine healthcare. We assumed that we would learn things that would also lead to changes in the basic outcome set. We therefore limited the use to a handful of countries as pilot locations. They have worked intensely over a 2-year period and learned together how to implement Key4OI. The pilot locations are HongKong SAR, Shenzhen China, Norway, Isala and UMC Utrecht in the Netherlands, Nemours hospital Wilmington USA and the Shriners Children’s Hospital in Montreal Canada. The pilots are implementing the set into their routine healthcare. We will also test satisfaction of patients and healthcare providers and seek to improve on the feedback we receive.

Which products have come out of Key4OI in total?

All the products can be found on www.key4oi.org. It includes the Orpha-net article, the reference guide with a data dictionary and 2 patient tools, a checklist for preparing for a visit to a multi-disciplinary team and a 1 page health action plan called “compass”.   We will translate the patient tools into different languages to support the use of Key4OI world-wide.  More tools and more support will become available over time.

The purpose of these tools was to boil the available information down to something that is practical and useful for people with OI, when managing their health. Both the compass and the checklist were predominantly developed with and through the OI community “end users”. But of course, we also had professionals providing input and feedback.

How can Key4OI play a role in clinical practise and clinical trials?

Key4OI can be used in routine clinical practice. Some locations may just use the patient tools, but may over time choose to capture the underlying data too. This will benefit the individual patient with OI as it helps healthcare providers with and without experience with OI to focus on the needs of the individual person with OI (not just the “bones”). Key4OI promotes multidisciplinary care throughout a lifetime. In the future, it may also serve to improve clinical practice. For example, healthcare providers could choose to compare how they are approaching psychosocial care for OI or pain and learn from each other, using 1 language and 1 consistent data set.

Ideally Key4OI would also be used in clinical trials. The simple thought is that clinical trials need to demonstrate that they make a significant difference to the health outcomes of people with OI. By using Key4OI it will become easier and faster to demonstrate the difference (as historical data will have built up already) and to compare across clinical trials. It would also be beneficial that the data that is collected, is collected for the long term benefit for the patient and OI and not just for the sake of the trial as such. It could also be used in regulatory processes with the same logic. It’s however important to say that Key4OI is not firmly linked to a registry. We are not collecting any data. We think that this needs to be managed by professional institutions.

What are the future plans? 

All the tools are freely available for everyone without a licence. Every country who wants to benefit from the knowledge exchange and being part of the Key4OI Learning Community needs to demonstrate that they are actually going to implement a significant part of Key4OI in a sustainable way.  If they can demonstrate this, we will mention them on our website as a “Key4OI location”. There is no commercial model involved. Only if used by commercial parties a fee may apply. We will discuss and agree on this together with our stakeholders.

Would it be an idea to develop OI specific outcome measures? 

Everything we do should be sustainable. Having a basic “demographic set” of outcome measures that is identical with other diseases makes sense. Having a disease specific set also makes sense as the outcomes in OI will be different from cancer. The most critical is that the measures used within the outcome set should be generic! The desire to develop measures from scratch for OI is very understandable, however extremely challenging as the measure would need to be validated across languages, different types of OI and age groups. This is the reason why we have chosen many PROMIS measurement tools. PROMIS has a strong scientific basis and has been widely used for many years. PROMIS is not perfect, but is proven effective in many conditions, it has been used with OI already in various hospitals, it is available for free, and for some areas available in more than 50 different languages.

Are there costs connected to some of the recommended tools?

There is no cost for the use of Key4OI for non-commercial purposes. PROMIS is free of costs for all the existing translations. Costs are only involved when a translation needs to be generated. It would be a once off fee.

OI in children and adults – same thing or 2 different planets?

Key4OI started out with developing a version for children and one for adults, as we were convinced that they would be very different planets. Throughout the process we found ca. 80% overlap and it became clear that many “adult issues” that don’t seem to play a key role for children, actually do start at a younger age. It will be tremendously useful to take a “lifelong perspective” for achieving the best outcomes for people with OI.

Any messages to the readers of OIFE Magazine?

There is just one advice: Please start using Key4OI!

• Download the checklist to support your next appointment if you are person with OI or a parent!
• Discuss Key4OI with your expertise centre if you are a patient organization. They are welcome to use it!
• Consider working with the Key4OI approach if you are a healthcare provider!
• Use the data that will eventually become available, if you are a researcher!
• Talk to us if you are an industry representative and you want to link up with Key4OI!

More information can be found on www.key4OI.org.

If you have any questions, please contact us on info@key4OI.org and join us in the virtual www.qualityoflife4oi.org conference on 12 February, which includes Key4OI as one of the information streams.