IRCCS San Raffaele Pisana, Rome, Italy, 28 February - 2 March 2018 Why do we need (register) and properly report results of human studies with biomarkers ? IRCCS San Raffaele Pisana, Rome, Italy, 28 February - 2 March 2018

“Eli Lilly & Co. urged doctors to prescribe Zyprexa for elderly patients with dementia, an unapproved use for the antipsychotic... after [it] sent study results to the U.S. Food and Drug Administration” showing Zyprexa didn’t alleviate dementia symptoms in older patients…”

Screen shot of Washington Post article Screen shot of Washington Post article. A Silenced Drug Study Creates An Uproar. By Shankar Vedantam Wednesday, March 18, 2009 “The results of Study 15 were never published or shared with doctors, even as less rigorous studies that came up with positive results for Seroquel were published and used in marketing campaigns aimed at physicians and in television ads aimed at consumers.” “The results of Study 15 were provided only to the Food and Drug Administration -- and the agency has strenuously maintained that it does not have the authority to place such studies in the public domain.” Screen shot of Washington Post article. A Silenced Drug Study Creates An Uproar. By Shankar Vedantam Wednesday, March 18, 2009

Screen shot of : The New England Journal of Medicine Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-Label Use S. Swaroop Vedula, M.D., M.P.H., Lisa Bero, Ph.D., Roberta W. Scherer, Ph.D., and Kay Dickersin, Ph.D. Screen shot of : The New England Journal of Medicine Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-Label Use S. Swaroop Vedula, M.D., M.P.H., Lisa Bero, Ph.D., Roberta W. Scherer, Ph.D., and Kay Dickersin, Ph.D. N Eng J Med. 2009 Nov 12;361:1963-71

Reasons to Register Clinical Trials and Report Results Human Subject Protections Allows potential participants to find studies Assists ethical review boards and others to determine appropriateness of studies being reviewed (e.g., harms, benefits, redundancy) Promote fulfillment of ethical responsibility to human volunteers – research contributes to medical knowledge Research Integrity Facilitates tracking of protocol changes Increases transparency of research enterprise Evidence Based Medicine Facilitates tracking of studies and outcome measures Allows for more complete identification of relevant studies Allocation of Resources Promotes more efficient allocation of resources

Levels of “Transparency” 6 Zarin DA, Tse T.. Science. 2008 Mar 7;319(5868):1340-2.

Advances in laboratory techniques have led to the increasing use of biomarkers in epidemiological studies, but the quality of reporting of such studies varies. The STROBE (STrengthening Reporting of Observational studies in Epidemiology) initiative, established in 2004, provides guidance on reporting observational epidemiology studies. Here, the STROBE-ME (Strengthening the Reporting of OBservational studies in Epidemiology – Molecular Epidemiology) initiative builds on STROBE and provides additional guidance on reporting biomarker studies. Gallo et al., PL0S Med, 2011

Specific additions relate to the collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. A checklist to help authors in reporting biomarker studies was published as supporting information.