How are Mobility Endpoints Used in Pivotal Clinical Trials?

Mobility loss is common, with about 1 billion people globally living with some form of mobility loss as a result of respiratory, cardiovascular, musculoskeletal, neurological or other issues. Its consequences are severe and go well beyond the physical. Loss of mobility can also have a profound impact on a person’s mental health, social role, social life and even their sense of identity.

Given the significant consequences, it would seem logical that mobility is routinely assessed when evaluating the impact of new therapies for conditions that have a significant impact on mobility. A study by Jager et al. (2022) looked at this issue by assessing the use of mobility as a decisive outcome for the marketing authorisation of drugs by the European Medicines Agency (EMA).

Prevalence of Mobility Endpoints in Pivotal Studies

The study looked at 15 therapeutic areas commonly impacting mobility, such as Parkinson’s, MS, COPD, heart failure and arthritis*. It assessed the primary and secondary endpoints referenced in 402 ‘main studies’ that supported a marketing authorisation decision by the EMA. The proportion of these studies using primary or secondary endpoints that considered mobility is shown below.

We can see that mobility was most commonly considered as a secondary endpoint only. Mobility is not assessed at all in 26% of studies, which appears odd given the prevalence of mobility loss in the 15 conditions included in the study. 31% of studies do consider mobility as a primary endpoint, but if we look at the individual endpoints, we can see that mobility is only a minor component of many of them.

Specificity of the Mobility Measures

The study found 153 primary and 584 secondary endpoints which considered mobility. There were 70 different assessment tools, and the study categorised these assessments into 3 groups in order to evaluate the extent to which the measures provided an independent and distinct assessment of mobility.

Category 1 – High level of distinct mobility information. These were measures that assessed mobility specifically (e.g. 6-minute walk test) or assessed it directly (e.g. asking the patient if they had difficulty walking 400 metres).

Category 2 – Moderate level of distinct mobility information. These included composite endpoints where mobility was assessed directly, but combined with other non-mobility factors in one overall score. It also included patient reported measures with a dimension/scale that specifically addressed mobility status (e.g.UPDRS II or MSQOL-54), but this score was contained within an overall summary score.

Category 3 – Low level of distinct mobility information. These included composite with a summary score combining both non-mobility items and mobility assessments from category 2 (e.g. ACR). It also included assessments/questionnaires with some mobility aspects, but no separate subscale on mobility measures.

The proportions of the 70 individual assessment tools that fell under the 3 categories are outlined below.

Data from Jager et al. (2022)

We can see that only 15.7% of tools were Category 1 and provided a high level of distinct mobility information. The majority of assessment tools were Category 3, and tended to be broader quality of life indicators with a minor mobility component. This makes the assessment of mobility very problematic as composite endpoints may have low scores for reasons unrelated to mobility.

Another striking aspect to note is that out of the all the 402 'main studies' analysed in the paper, not one study included a digital mobility outcome. 

Conclusion

We can see that mobility indicators are underutilised when it comes to pivotal trials for marketing authorisation by the EMA. Where they are used, they tend to be unspecific measures that provide a partial view of mobility at best. There may be many reasons for this, including the shortcomings of many traditional measures of mobility (we discuss these in our White Paper on “Why Real World Mobility Matters”, available at https://www.enoda-health.com/ ).

If mobility loss is to be addressed in a more comprehensive way, we need better and more specific measures of mobility being routinely used in trials for conditions impacting mobility. At Enoda, we believe that real world mobility data using the technologies developed in Mobilise-D (Home - Mobilise-D) can provide better, richer, more relevant and patient-centric data for clinical trials. It can also provide for more individualised care, provide greater scope for early intervention, enhance remote care and empower patients with better and more timely data. 

Mobility loss is a major issue that has been has not been adequately addressed to date, as we can see from the data above. Real-world mobility data has the potential to change that, and Enoda has been founded to make it happen. 

Contact us at info@enoda-health.com if you would like to know more. 

* The 15 conditions were ankylosing spondylitis, asthma, COPD, diabetic neuropathies, fibromyalgia, gout, heart failure, multiple sclerosis, obesity, osteoporosis, Parkinson’s disease, pathologic fractures, pulmonary hypertension, rheumatoid arthritis and visual disorders.

 ** The data is based on Jager et. Al (2022) who assessed the primary and secondary endpoints referenced in 484 European Public Assessment Reports (EPARs) published by the EMA until September 2020 for the 15 conditions above. EPARs are reports that summarise the information supporting a decision related to marketing authorisation. These 484 EPARs referenced 402 ‘main studies’ that are the basis of the data in the graph.