The Transthyretin Amyloidosis Outcomes Survey (THAOS) registry: design and methodology

Abstract

Background:

Transthyretin (TTR) amyloidosis – the most common type of hereditary amyloidosis – also has an acquired form and is observed in geographically dispersed populations. TTR amyloidosis is marked by considerable clinical heterogeneity, and the main phenotypes are neurologic and cardiovascular.

Methods:

THAOS is an international, noninterventional, longitudinal, observational registry designed to evaluate overall survival in patients, better understand genotype–phenotype relationships and the natural history of TTR amyloidosis, and evaluate the effects of liver transplantation and other treatments on disease progression in TTR amyloidosis. All individuals with a confirmed TTR mutation with or without a diagnosis of TTR amyloidosis and patients with wild-type TTR amyloidosis are eligible to be enrolled in the registry.

Purpose:

To describe the design and methodology of the recently established registry. Procedures for data collection are outlined and a minimum set of assessments for the standard evaluation of all subjects with TTR amyloidosis is described. Demographic information, TTR genotype, medical history, family history of the disease, and transplant history are assessed at baseline. On return visits, signs and symptoms of the disease are evaluated, general examinations are conducted, and laboratory data, measures of neurologic and cardiovascular function, and quality of life are assessed according to the standard of care for patients. Visits on at least a biannual basis are recommended. The registry will remain open for a period of at least 10 years.

Results:

The initial experience suggests that the registry is characterized by a comprehensive set of data elements which can be completed by providers from the various clinical backgrounds who administer care to individuals with TTR amyloidosis.

Conclusion:

As of September 2011, 30 centers in 15 of the 19 countries participating in the THAOS registry have enrolled 975 patients. Such data provide a representative sample of the global TTR amyloidosis patient population, including asymptomatic TTR variant carriers, which can inform the natural history of the disease and offer the potential to evaluate novel therapeutic modalities in diverse patient subpopulations.

Trial registration: ClinicalTrials.gov identifier: NCT00628745.

Key words::

• Amyloidosis
• Cardiomyopathy
• Familial amyloid polyneuropathy
• Methodology
• Neuropathy
• Registry
• Transthyretin

Transparency

Declaration of funding

Data for this manuscript are derived from the THAOS registry (NCT00628745), which is sponsored by Pfizer Inc.

Declaration of financial/other relationships

V.P.-B. has received support from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010, as a clinical investigator, and has served on the THAOS (natural history disease registry) scientific advisory board. O.B.S. served as an advisor for Alnylam Pharmaceuticals, Isis Pharmaceuticals, and Pfizer Inc., in addition to having served as an advisor and receiving support as a clinical investigator from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010. M.S.M. has received support from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010, as a clinical investigator and for scientific meeting expenses (travel, accommodations, and registration). At the time of manuscript development, B.W. was an employee of FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010. At the time of manuscript development, D.R.G. was an employee of FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010. T.C. has received support from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010, as a clinical investigator and for scientific meeting expenses (travel, accommodations, and registration).

CMRO peer reviewers 1 and 3 have no relevant financial relationships to disclose. CMRO peer reviewer 2 has in the past received grant support from Pfizer.

Acknowledgment

Editorial/medical writing support was provided by Stephen Towers PhD and Ali Shandiz PhD at Scientific Strategy Partners and was funded by Pfizer Inc.