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. 2023 Dec;13(12):e3331.
doi: 10.1002/brb3.3331. Epub 2023 Nov 13.

Natural history of Duchenne muscular dystrophy in the United Kingdom: A descriptive study using the Clinical Practice Research Datalink

Jonathan Broomfield  1 , Keith Abrams  2   3 , Nick Latimer  4 , Michela Guglieri  5 , Mark Rutherford  1 , Michael Crowther  6
Affiliations

Natural history of Duchenne muscular dystrophy in the United Kingdom: A descriptive study using the Clinical Practice Research Datalink

Jonathan Broomfield et al. Brain Behav. 2023 Dec.

Abstract

Background: Duchenne muscular dystrophy (DMD) is a rare, muscle-degenerative disease predominantly affecting males. Natural history models capture the full disease pathway under current care and combine with estimates of new interventions' effects to assess cost-effectiveness by health technology decision-makers. These models require mortality estimates throughout a patient's lifetime, but rare disease datasets typically contain relatively few patients with short follow-ups. Alternative (published) sources of mortality data may therefore be required.

Methods: The Clinical Practice Research Datalink (CPRD) was evaluated as a source of mortality and natural history data for future economic evaluations of health technologies for DMD and rare diseases in general in the UK population. This retrospective longitudinal cohort study provides flexible parametric estimates of mortality rates and survival probabilities in the current UK DMD population through primary/secondary records in the CPRD since 1990. It also investigates clinically significant milestones such as corticosteroid use, spinal surgery, and cardiomyopathy in these patients.

Results: A total of 1121 male patients were included in the study, observed from 0.7 to 48.9 years. Median life expectancy was 25.64 years (95% confidence interval 24.73, 26.47), consistent with previous global estimates. This has improved to 26.47 (25.16, 27.89) years in patients born after 1990. The median ages at corticosteroid initiation, spinal surgery, ventilation, and cardiomyopathy diagnosis were 6.06 years (5.77, 6.29), 14.79 years (14.29, 15.09), 16.97 years (16.50, 18.31), and 15.26 years (14.22, 16.70), respectively.

Conclusions: Estimates of mortality in UK-based DMD patients are age-specific in a uniquely large and nationally representative sample from the CPRD.

Keywords: Duchenne muscular dystrophy; economic models; electronic health records; statistical models.

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Conflict of interest statement

Jonathan Broomfield, Keith Abrams and Michael Crowther have received consultancy fees from Duchenne UK. Michela Guglieri has received research funding from Sarepta, PTC, Muscular Dystrophy UK, NIH and H2020; is (or has been) chief investigator/principal investigator for clinical trials of Pfizer, Italfarmaco, Santhera, Roche, ReveraGen, Dynacure, Dyne; is a member of Advisory boards for Pfizer, NS Pharma, Dyne (honoraria through Newcastle University); and has received speaker honoraria from Sarepta, Italfarmaco, Novartis and Roche.

Figures

FIGURE 1
FIGURE 1
Flow of patients in the study. *Numbers taken from Clinical Practice Research Datalink (CPRD) website (CPRD GOLD, ; CPRD Aurum, 2021). HES, Hospital Episode Statistics; ONS, Office for National Statistics.
FIGURE 2
FIGURE 2
Random sample of ages, ages at first corticosteroid use, and ages against calendar time of 300 patients from the Clinical Practice Research Datalink (CPRD) (150 each from GOLD/Aurum) from 1990 onward.
FIGURE 3
FIGURE 3
Flexible parametric predictions of (a) survival in the Clinical Practice Research Datalink (CPRD) cohort, and (b) changes in survival over time, left‐truncated at practice registration dates. Also overlain for the whole cohort are Kaplan–Meier (KM) estimates and estimates from a review of international studies (Broomfield et al., 2021). CI, confidence interval.
FIGURE 4
FIGURE 4
(a) Net probabilities and (b) cumulative incidence functions of experiencing clinical milestones if patients have not yet died and before they die, respectively.
FIGURE A1
FIGURE A1
Mortality rates in the Clinical Practice Research Datalink (CPRD) cohort, with overlain estimates from a review of international studies (Broomfield et al., 2021) and from the UK general population, and changes in these rates over time.
See this image and copyright information in PMC

References

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