ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder

Abstract

Summary Geographically dispersed patients, inconsistent treatment tracking, and limited infrastructure slow research for many orphan diseases. We assess the feasibility of a patient-powered study design to overcome these challenges for Castleman disease, a rare hematologic disorder. Here, we report initial results from the ACCELERATE natural history registry. ACCELERATE includes a traditional physician-reported arm and a patient-powered arm, which enables patients to directly contribute medical data and biospecimens. This study design enables successful enrollment, with the 5-year minimum enrollment goal being met in 2 years. A median of 683 clinical, laboratory, and imaging data elements are captured per patient in the patient-powered arm compared with 37 in the physician-reported arm. These data reveal subgrouping characteristics, identify off-label treatments, support treatment guidelines, and are used in 17 clinical and translational studies. This feasibility study demonstrates that the direct-to-patient design is effective for collecting natural history data and biospecimens, tracking therapies, and providing critical research infrastructure.

Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease

“…Any patient who has received a pathology report suggestive of Castleman disease can self‐enroll in the natural history registry. Previously, it was reported that ACCELERATE is skewed towards more symptomatic and less easily treated patients, who are more likely to seek out resources online 26 . Accordingly, ACCELERATE is likely biased towards a higher iMCD‐TAFRO population than the general iMCD population, as these patients typically have a more severe and unpredictable clinical course and may be more likely to seek out resources.…”

“…Previously, it was reported that ACCELERATE is skewed towards more symptomatic and less easily treated patients, who are more likely to seek out resources online. 26 Accordingly, ACCELERATE is likely biased towards a higher iMCD-TAFRO population than the general iMCD population, as these patients typically have a more…”

“…Tables2 and 3summarize and compare iMCD-TAFRO/TAFRO syndrome criteria and iMCD criteria proposed to date, respectively. To evaluate the applicability of this definition of iMCD-TAFRO in an independent cohort, we interrogated the patient-powered arm of the ACCELERATE Natural History Registry26 to identify the proportion of iMCD patients who would T A B L E 4 (Continued)…”

The disease course of Castleman disease patients with fatal outcomes in the ACCELERATE registry

“…There is a paucity of data describing the natural history of all forms of CD and limited data related to outcomes and prognosis 4,26 . ACCELERATE is an international natural history registry established in 2016 to collect real‐world data on patients with CD 20,27 . Patients who have received a pathological CD diagnosis can enrol online (http://www.cdcn.org/ACCELERATE) from anywhere in the world or through one of nine sites in Europe.…”

Increased mTORC2 pathway activation in lymph nodes of iMCD‐TAFRO

“…Diagnostic lymph node samples were obtained from iMCD patients enrolled in the ACCELERATE Natural History Registry (NCT02817997). 17 All subjects gave written informed consent, and the studies were approved by local institutional review boards in accordance with the provision of the Declaration of Helsinki and Good Clinical Practice Guidelines. Tissue from eight iMCD‐NOS and eight iMCD‐TAFRO patients was procured following formalin‐fixation paraffin embedding (FFPE).…”