Being PRO-ACTive: What can a Clinical Trial Database Reveal About ALS?

Abstract

Advancing research and clinical care, and conducting successful and cost-effective clinical trials requires characterizing a given patient population. To gather a sufficiently large cohort of patients in rare diseases such as amyotrophic lateral sclerosis (ALS), we developed the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) platform. The PRO-ACT database currently consists of >8600 ALS patient records from 17 completed clinical trials, and more trials are being incorporated. The database was launched in an open-access mode in December 2012; since then, >400 researchers from >40 countries have requested the data. This review gives an overview on the research enabled by this resource, through several examples of research already carried out with the goal of improving patient care and understanding the disease. These examples include predicting ALS progression, the simulation of future ALS clinical trials, the verification of previously proposed predictive features, the discovery of novel predictors of ALS progression and survival, the newly identified stratification of patients based on their disease progression profiles, and the development of tools for better clinical trial recruitment and monitoring. Results from these approaches clearly demonstrate the value of large datasets for developing a better understanding of ALS natural history, prognostic factors, patient stratification, and more. The increasing use by the community suggests that further analyses of the PRO-ACT database will continue to reveal more information about this disease that has for so long defied our understanding.

Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel

“…Database studies can provide valuable epidemiological information, which should be used in conjunction with patient-reported outcomes measuring the quality of life with ALS. Further studies are needed to assess the risk factors for ALS, to study the heterogeneity of ALS and model disease progression using real-world data and ALS Clinical Trials database [36]. …”

Predicting functional decline and survival in amyotrophic lateral sclerosis

“…This database is named The Pooled Open Access Clinical Trials Database (PRO-ACT) (www.ALSDatabase.org)[4, 5]. It includes data on all variables such as biomarkers that were collected in the individual studies.…”

The changing picture of amyotrophic lateral sclerosis: lessons from European registers

“…Some clinical trial-based datasets (eg, ProACT (https://nctu.partners.org/ProACT)) have suggested that survival of ALS patients has increased over time,22 an effect that has been attributed in part to increased use of interventions such as non-invasive ventilation. However, while there is evidence that non-invasive ventilation may affect survival in some patients, data from European population-based registers have not identified a significant overall effect on survival at population level since the inception of non-invasive ventiliation (NIV) as a standard of care in ALS management 11 21.…”