Clinical Trial ResultsSharing Results, Speeding Discoveries

Ann Murphy, PhDManaging Editor

February 19, 2015

Clinical Trial Results (CTR)

Every clinical trial, regardless of outcome, embeds important research information• CTR enables transparent and consistent reporting of all clinical trial

results• CTR’s brief, standardized format:

– 1-2 page Author Summary in print– Additional data online, including AEs, PK/PD, and Extended Discussion– CTR is fully indexed by PubMed, ensuring thorough access to results worldwide

Goal: To encourage the reporting of all clinical trial results

Median lag between trial completion and publication is 23 months – BMJ, Jan 2012

Less than 25% of registered trials publish results within a year of completion. – JAMA, Feb 2012

Clinical Trial Results

PhRMA, EFPIA: Principles for Responsible Clinical Trial Data Sharing

“All company-sponsored clinical trials should be considered for publication in the scientific literature irrespective of whether the results of the sponsors’ clinical trials are positive or negative.”

PhRMA, EFPIA. Principles for Responsible Clinical Trial Data Sharing, 2013. http://www.phrma.org/sites/default/files/pdf/PhRMAPrinciplesForResponsibleClinicalTrialDataSharing.pdf

Clinical Trial Results:Co-Creators & Co-Editors

Antonio Tito Fojo, MD, PhDHead, Experimental Therapeutics SectionCenter for Cancer Research

Susan E. Bates, MDHead, Molecular Therapeutics SectionCancer Therapeutics Branch

Benefits to Authors:

– Easy submission process– Rapid review and

publication– No publication fees– Open Access publication

format– Author Summaries are

fully translated into Chinese

– Authors retain the copyright to the online data

Benefits to Readers:

– Open Access on the leading ePublishing platform HighWire Press®

– Concise, easy-to-read format

– More published trials to learn from and to advance research

– Full searchability

Clinical Trial Results

Looking Ahead: Near-Term Goals

– Phase III Trials• Enhancements to the functionality of the submission site will

allow for the publication of Phase III trials– “Lessons Learned”

• Investigators will share important takeaway messages from their trials in this new feature to be printed in the Author Summary and further explained in the extended Discussion in the full data set online.

– Enhanced Searchability • Through continuing partnership with HighWire Press,

additional support for more precise searching will further enhance CTR’s mission to share results

Clinical Trial Results

Some Stats:• 46 different chemotherapeutics and targeted agents• 14 cancer types

– Breast = 19%– Lung = 15%– CRC = 12%

Clinical Trial Results

Europe US Asia Phase I Phase II Randomized Single Arm

22 21 8 9 43 11 41

Online Data Set (excerpt)

Clinical Trial Results

Author Summary

• Menu-driven format– No manuscript preparation required– Data fields with drop-down choices and free text allow

you to accurately and efficiently describe your trial and its results

• Automatically creates Kaplan-Meier survival curves, waterfall plots, and toxicity tables

Bring Your Data

Bring Your Data

Bring Your Data

Bring Your Data

Bring Your Data

Clinical Trial ResultsK-M data entry

Resulting graph

Kaplan-Meier

Waterfall Plot

Enter +/- tumor shrinkage per patient

Resulting graph

Adverse EventsAE data entry

Resulting table, percentages calculated per grade

• Collection now includes 50+ trials• Repeat authors• Big Tent Strategy• Low reject rate = more data to share

• Online collection powered by

RECENT TITLES: Phase I Dose-escalation Study of Pilaralisib (SAR245408, XL147), a Pan-class I PI3K Inhibitor, in Combination With Erlotinib in Patients With Solid Tumors

A Phase II Study of a Dose-Density Regimen With Fluorouracil, Epirubicin, and Cyclophosphamide on Days 1 and 4 Every 14 Days With Filgrastim Support Followed by Weekly Paclitaxel in Women With Primary Breast Cancer

Clinical Trial Results: A Randomized Phase II Study of Carboplatin With Weekly or Every-3-Week Nanoparticle Albumin-Bound Paclitaxel (Abraxane) in Patients With Extensive-Stage Small Cell Lung Cancer

Clinical Trial Results

#50

Clinical Trial ResultsPublished Trials from Chinese Investigators

S-1 as Monotherapy or in Combination With Leucovorin as Second-Line Treatment in Gemcitabine-Refractory Advanced Pancreatic Cancer: A Randomized, Open-Label, Multicenter, Phase II Study S-1单药或联合亚叶酸钙作为吉西他滨难治性晚期胰腺癌的二线治疗：一项随机、开放标签、多中心、 II期研究Feijiao Ge et al.

Phase II Study of Afatinib as Third-Line Treatment for Patients in Korea With Stage IIIB/IV Non-Small Cell Lung Cancer Harboring Wild-Type EGFR 阿法替尼作为三线治疗用于罹患含有 EGFR野生型 IIIB/IV期非小细胞肺癌韩国患者的 II期研究Myung-Ju Ahn et al.

The Multicenter, Phase II Prospective Study of Paclitaxel Plus Capecitabine as First-Line Chemotherapy in Advanced Gastric Carcinoma 紫杉醇联合卡培他滨作为晚期胃癌一线化疗的多中心、 II期前瞻性研究Jifang Gong et al.

Forthcoming:Phase II study of recombinant anti-tumor and anti-virus protein injection compared with placebo in metastatic colorectal cancer after failure of standard treatmentJian-Ming Xu et al.

“Without access to complete information … duplicative studies may be initiated that unnecessarily put patients at risk or expose them to interventions that are known to be ineffective for specific uses … Both real and potential harm can result from failure to fully disclose the results of clinical trials.”

“It is time to embrace an era in which transparency and responsible data sharing are common values.”

“NIH is committed to ensuring transparency around every NIH-supported clinical trial. … Timely reporting of clinical trials will be taken into consideration during review of subsequent applications for funding.”

Clinical Trial Results: NIH Takes a Firm Stand

-- Hudson, KL & Collins, FS. Sharing and reporting the results of clinical trials. JAMA, 2014

Clinical Trial Results

Marcia McNutt, PhD, Editor-in-Chief, SCIENCE“Data, eternal”. SCIENCE, 347;6217, 2015

“Interpretations come and go …

… but data are forever.”

Clinical Trial ResultsSharing Results, Speeding Discoveries

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