Artikel
A mix of healthcare claims analysis and simulation to offer first time estimates of incidence and prevalence of ATTR-CM in Germany
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Veröffentlicht: | 26. Februar 2021 |
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Background: Amyloidosis involves deposition of misfolded proteins that builds up in organs resulting in disfunctions. Amyloidosis is classified based on the proteins involved. Transthyretin-related amyloidosis (ATTR) is caused by deposits of TTR, a transport protein for thyroxine and vitamin A produced by the liver. Depositions in the heart results in ATTR cardiomyopathy (ATTR-CM), a rare and progressive disease. The average survival time after diagnosis on symptomatic treatment, is estimated to be 2-5 years [1], [2], [3], [4]. A systematic literature review revealed the absence of information on the overall epidemiology of this rare condition in the German population.
Methods: A retrospective cohort study using German healthcare claims data on a representative sample of 4 million patients over 6 years was performed to assess the incidence of ATTR-CM. Since there is currently no Code in the International Classification of Diseases 10th Revision (ICD-10) for ATTR-CM in Germany, a proxy was created which is a combination of ICD-10 for Amyloidosis and CM, considered in a time-dependent fashion. An Operation and Procedure (OPS) code was also required to exclude suspicious cases. Four study years were examined separately, including a baseline period of two years. The proportion of incident cases in the database was used to extrapolate the results to the entire adult German population. Prevalent cases were simulated using a multistate model with two possible states: “diagnosed” and “dead”. Entry data for the simulation were (i) the number of incident cases from the claim analysis and (ii) the mortality hazard rate per year of the placebo arm of the ATTR-ACT study as the transition probability between states. The Markov property was assumed: survival times were constant and independent from the past. Every year, survival times were simulated for each incident patient. New and alive prevalent cases were summed up to assess yearly prevalence. The simulation was run over 50 years and repeated 500 times to get bootstrapped confidence intervals.
Results: Estimated incidence of ATTR-CM for the adult German population for 2014 to 2017 was 372 [212; 603], 442 [266; 691], 282 [146; 493] and 328 [180; 551] cases respectively. It took the simulation 27 simulation years to stabilize around 1920 prevalent ATTR-CM patients currently in Germany.
Conclusion: Even if the lack of proper IDC-10 for ATTR-CM adds uncertainty to the definition of cases, we were able to retrieve realistic estimates of incident cases. The methodology remained challenging for prevalence estimates: with no treatment option, rare specialized cardiologists and older age at diagnosis, prevalent patients are unlikely to consult on a regular basis for this indication and might remain uncaptured by a design that requires a repeated diagnosis at least once a year. Plausible results were retrieved by simulation, in line with the perception of KOLs. However, diagnosis of ATTR-CM is known to be difficult and often mixed up with other forms of cardiomyopathy. The true number of cases in the population is likely to be much higher than the number of diagnosed patients.
The authors declare that they have no competing interests.
The authors declare that an ethics committee vote is not required.
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