Natural history model estimates Duchenne MD trajectory

Model introduces new 'transfer' state as key stage in disease progression

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

A person stands next to an egg timer as the sand runs out, illustrating a natural history model.

It may take an average of 11 years before people with Duchenne muscular dystrophy (DMD) lose upper body function and the ability to breathe on their own, according to a study by researchers of the HERCULES project, which set out to construct a natural history model of the disease to support cost evaluations of new therapies.

“The natural history model provides data to inform disease progression under standard of care for economic evaluations of new therapies in Duchenne muscular dystrophy,” the researchers wrote in “Developing a Natural History Model for Duchenne Muscular Dystrophy,” which was published in PharmacoEconomics-Open. The study was funded by the Duchenne UK charity.

DMD is a progressive form of muscular dystrophy caused by a lack of dystrophin, a protein that normally protects muscles from damage during the regular wear and tear of movement. As a result, muscles become weak and waste away over time. As part of their natural history model, that is, a model about how a disease progresses, the researchers predicted people with DMD have a median survival of 34.8 years.

Standard of care usually involves taking oral corticosteroids such as prednisone to reduce inflammation, slow muscle weakness progression, and delay breathing problems.

As other treatment options enter the market, their benefit must be proved, often through a cost-effectiveness analysis. Not enough data on the natural history of DMD  is available to support such an analysis, however.

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 Importance of ‘transfer’ state in DMD trajectory

The HERCULES project is a collaborative effort involving various stakeholders. As part of it, the researchers built a new natural history model that considers a patient’s experience over his lifetime under current standard of care.

The primary source of data was the Critical Path Institute Duchenne Regulatory Science Consortium (D-RSC) database, which includes data from 11 international sources such as clinical trials and registries. The researchers also drew on doctors, patients, and caregivers along with mortality data from 14 studies.

The model covers an ambulatory state, where patients begin to lose the ability to stand and walk; a transfer state, where patients are no longer able to walk, but still support their own weight to facilitate transfers, such as between wheelchair and toilet; and a nonambulatory state, marked by loss of hand-to-mouth and breathing function.

Previous models didn’t include a transfer state, which “was identified by patients and caregivers as a key stage in the progression of DMD due to its impact on quality of life, care support requirements, and cost,” the researchers wrote. Once being able to facilitate transfers is lost, “additional resources are required to transfer patients and the burden on caregivers increases.”

The model estimated patients spend a mean of 9.5 years in the ambulatory state, 1.5 years in the transfer state, and the remainder of their lives in the non-ambulatory state.

“The model includes a detailed disease pathway for DMD, including the clinically and economically important transfer state,” the researchers said, adding it may help “estimate the current trajectory of DMD in economic evaluations of new treatments.”