Being PRO-ACTive: A Collaborative Effort to Bring Big Data to ALS. Alex Sherman, Melanie Leitner, Prize4Life

Transcription

1 Being PRO-ACTive: A Collaborative Effort to Bring Big Data to ALS Alex Sherman, NCRI@MGH Melanie Leitner, Prize4Life

2 What is ALS (Lou Gehrig s Disease)? Orphan disease 100% lethal within 2-5 years from diagnosis (respiratory failure) Only existing FDA-approved treatment prolongs life by 2-3 months Affects both men and women and can strike at any adult age Expensive disease costing $ ,000/year in direct costs Avi ~ 9 months post-diagnosis Avi ~3 years post-diagnosis

3 The Goals of the PRO-ACT Project PRO-ACT = Pooled Resource Open-Access ALS Clinical Trials Database To obtain subject records from completed Phase II/III ALS clinical trials; Clean, harmonize, aggregate and anonymize data; Make the anonymized dataset available to the global R&D community to: Enable scientists and clinicians to learn more about the disease; Increase the likelihood of success of ALS clinical trials; Reduce the cost required to determine drug effectiveness

4 Who Are Our partnersforcures?

5 Prize4Life Prize4Life is an innovative, results-oriented 501(c)(3) not-for-profit organization focusing exclusively on Amyotrophic Lateral Sclerosis (ALS) Our mission is to accelerate the discovery of treatments and a cure for ALS by using powerful incentives to attract new people and drive innovation. Prize4Life has embraced the Incentive Prize Model as part of its portfolio of strategies to change the landscape for ALS research In addition, Prize4Life has focused on high-impact research infrastructure projects designed to enhance and accelerate translational efforts

6 Who Are Our partnersforcures?

7 NCRI s mission is to accelerate translational research in neurological disorders by: Mapping the clinical development of potential therapies; Custom design of clinical research protocols; Establishing and managing disease-specific research consortia (NEALS, ALD Connect); Designing, deploying and managing registries, repositories and biobanks; Providing resources, staff, and services to conduct clinical trials and research; Fostering and empowering scientific collaboration; Educating and mentoring future leaders in the field of clinical research; NCRI also serves as: Clinical Coordinating Center for NeuroNEXT, a NIH-supported network for phase II clinical trials in neurology; Data Coordinating Center (DCC) for the NIH-funded Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS); DCC for the Rapidly-Acting Treatments for Treatment-Resistant Depression (RAPID) network; ACRO for 20+ clinical trials and studies in CNS diseases.

8 Who Are Our partnersforcures?

9 PRO-ACT Timeline Proposal Funding 2011 Data sources identification 2011 Legal agreement 2011 Getting the data 2011 Platform development Data Cleaning Harmonization Anonymization Import Launch Dec Analyses & crowdsourcing NOW!

10 Data Workflow Define Common Data Structure (CDS) Analyze individual datasets Map elements from individual datasets to CDS elements Import Data Analyze/Crowdsource

11 PRO-ACT Platform

12 Over 180 requests from 21 countries PRO-ACT Users 64% -PhD/MD 13 pharma companies 14 informatics companies 58+ academic institutions 3 government entities

13 Impacts of PRO-ACT on ALS R&D CONFIDENTIAL Scientific Benefits: Understanding of natural history and disease heterogeneity Novel biomarkers and pathways of disease Clinical Development Benefits Simulations Test stratification theories Reduce the cost of future ALS clinical trials Explore link between disease progression and medication use Other Benefits Grow quantitative workforce with interest in/exposure to ALS data

14 The ALS Prediction Prize: An Early Effort to Translate Big Data into Health

15 The ALS Prediction Prize: A Case Study for Big Data To bring attention to PRO-ACT and to ALS from quantitative communities worldwide we launched an incentive prize: Project Rational: There is currently no effective mechanism to predict ALS progression so as to be able to stratify rapid and slow ALS progressors Enabling earlier and more reliable prediction: would improve clinical trials by helping to account for heterogeneity within the ALS population (less variability fewer patients needed easier, less expensive more interpretable clinical trials effective treatment faster) could improve clinical practice in ALS by enabling earlier use of palliatives and better life-planning by patients and their families

16 The ALS Prediction Prize: A Case Study for Big Data Project Implementation: Approach: We launched a $25,000 prize for the best prediction algorithm(s) that could take 3 months of patient clinical data and use this to predict the progression of a given patient s disease over the following 9 months Timeline: 3 months for competitors to develop and test algorithms Partners: The DREAM Project, Innocentive, NCRI, The Bowen Family, and brilliant quantitative minds around the world

17 The ALS Prediction Prize: A Case Study for Big Data Teams Around the World Competed for the Prize: 1073 solvers from 64 countries

18 The ALS Prediction Prize: A Case Study for Big Data Results: 37 unique algorithm solutions submitted $50K in prizes awarded New tools (currently being tested by companies) Modeling suggests use of the algorithms would reduce the number of patients needed to see a treatment effect by 23% in clinical trials Multiple novel predictors identified The ALS Prediction Prize program generated several high quality algorithms with the potential to assess ALS progression sooner and more reliably than current clinical practice

19 PRO-ACT Future Identify and solicit more data from clinical trials, both industry and academic (> 10 datasets are identified for their inclusion into PRO ACT in the nearest future); Secure funding for data aggregation and for maintenance and support of the platform and infrastructure; Provide data analytical services to the research community; Ensure visibility of PRO ACT resource through an outreach program; Create another challenge to attract researchers outside ALS and even medical communities; Prove feasibility of a crowdsourcing model for medical discoveries in rare diseases; Expand platform s utilization and know how to other diseases.

20 Importance of PRO-ACT Project The PRO-ACT platform is a resource available to the clinical research community through the efforts of a unique partnership among nonprofits, academic centers, and industry; By sharing and pooling data you can answer new questions and gain new insights into diseases, especially rare ones; Crowdsourcing is a great way to expand the pool of innovative thinkers and approaches available to address a difficult problem; If you are thinking of building a clinical database or running an incentive prize in your disease of interest, Prize4Life and NCRI can help!

21 PRO-ACT Collaboration Score (p4c) Academia Non-profit Charity Industry PEOPLE Academia Non-profit Charity Industry PEOPLE

22 partnersforcures Prize4Life Avi Kremer, CEO Shen Bennett Jessica Goodman, PhD Thomas Leavitt Melanie Leitner, PhD Guadalupe Martinez Neta Zach, PhD ALS Prediction Prize Collaboration Rebecca Betensky, PhD (HSPH) Robert Kueffner, PhD (DREAM) Raquel Norel, PhD (DREAM) Gustavo Stolivitsky (DREAM) Orla Hardiman, MD (Dublin) NEALS/NCRI Merit Cudkowicz, MD Nazem Atassi, MD James Berry, MD Igor Katsovskiy David Schoenfeld, PhD Alex Sherman Amy Shui Ervin Sinani Jason Walker With funding from the

23 BE YOURS. THANK YOU PRO-ACT can be found at: