How to Apply for and Receive Industry Funding for Investigator Sponsored Research Chuck Simonton MD, FACC, FSCAI Chief Medical Officer Abbott Vascular Santa Clara, CA, USA CRT 2013

Chief Medical Officer Abbott Vascular, Santa Clara, CA Charles A. Simonton, MD Chief Medical Officer Abbott Vascular, Santa Clara, CA

Investigator Sponsored Study (ISS) Sponsor-Investigator means an individual who both initiates and actually conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any person other than an individual, i.e., corporation or agency Investigator-Sponsored Study means that for trials with FDA-regulated products, the Investigator acts as a Sponsor-Investigator. This is an individual (not a corporation) who both initiates (plans and designs) and conducts an investigation, and under whose immediate direction the investigational drug/device is administered or dispensed. In addition to the standard investigator responsibilities, they will: plan, design, conduct, and monitor the study; manage data; prepare reports; and provide oversight, monitoring, and compliance with FDA-reporting requirements

Guidelines for ISS Research ISS research should be for the sole purpose of advancing science and/or clinical practice in a therapeutic area in which the Company holds interest The Company may inform independent investigators of the general areas of scientific or clinical interest, but not specific hypotheses or protocols The scientific study protocol must be written in full by the sponsor-investigator The sponsor-investigator is responsible for the conduct of the study including all aspects (IRB approvals, subject screening + enrollment + follow-up, data collection, analysis, and all regulatory reports according to the country’s requirements)

Guidelines for ISS Research The Office of the Inspector General (U.S. OIG) acknowledges the appropriateness of IISR when it serves the legitimate advancement of science in a therapeutic area and not the advancement of marketing objectives. The guidance specifically states “To reduce risk, manufacturers should insulate research grant making from sales and marketing influences.”1 1. Office of Inspector General, Health and Human Services, Compliance Program Guidance for Pharmaceutical Manufacturers, April 2003, accessed from the internet via http://www.oig.hhs.gov/fraud/docs/complianceguidance/042803pharmacymfgnonfr.pdf

Investigator Sponsored Study (ISS): What the Sponsor-Investigator Must Do Initiate the original concept and hypothesis for the study Author the full protocol for the study including all methods, design data collection, ensure quality of data, design the statistical analysis plan, patient follow-up procedures, study completion and publication plan Assume full responsibility for the conduct of the study Adhere to all legal and regulatory policies for the specific country; in the U.S. determine whether an IDE will be needed or other FDA requirements Prepare a budget proposal to cover related expenses for the study with careful consideration of fair market value (FMV) Comply with public transparency by registering study on www.clinicaltrials.gov

Guidelines for ISS Research: What Companies Must Do Provide investigators with general areas of interest in scientific and clinical research consistent with their product strategies Perform an internal scientific review of the ISS protocol to make sure it satisfies proper level of scientific standards and protects patient safety before approving grant support Review budget to ensure fair market value (FMV) Evaluate sponsor-investigator’s expertise, qualifications and resources to be sure the capabilities exist to complete the study

Guidelines for ISS Research: What Companies Must Do Perform periodic reviews of the study progress to ensure the research grant is being executed according to the contract Publicly disclose financial arrangements with investigators or hospital institutions for transparency Other Scientific and Legal/Regulatory Considerations Data privacy (in the U.S. HIPAA guidelines) Human Subject Recruitment and participation Applicable laws on payment to investigators Other local legal/regulatory requirements

Investigator Sponsored Research (ISS): Tips for Success in the Review Process First, decide which companies have an interest in the scientific or clinical research project you are considering; you can find this out by contacting the Medical Affairs persons covering your area; the closer your study aligns with the clinical strategy of the company, the more likely your study will be approved Next, inquire whether a “concept” proposal can be reviewed by the company before spending the time and resources to compose a complete protocol; If the concept is strategically aligned with the company, then a full protocol can be submitted which includes hypothesis, methods, number of subjects and duration of follow-up, biostatistical plan, and any pre-specified subgroups or analysis, and publication plan

Investigator Sponsored Research (ISS): Tips for Success in the Review Process Be sure the budget has been carefully vetted with your institution and that it contains competitive costs that represent fair market value (FMV) Respond quickly to questions from the company on scientific and methodology issues, and be open to constructive feedback; this is usually, in our experience, related to statistical analysis plans Check with the IRB for their support before beginning the long process of protocol development, and determine if FDA will require any special registration or reporting (such as an IDE) Inform the medical center’s legal department of the study protocol and upcoming contract with the company

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