Yale University Open Data Access (YODA) Project
Request for Proposal (RFP) Q&A
This page contains responses to questions that have been raised since the release of the RFP. Please submit additional questions to firstname.lastname@example.org. Thank you for your interest in the Yale University Open Data Access Project.
Question: We would like to clarify if the project budget and justification, projected timeline, anticipated challenges and plan for human subjects protection should be included in the 8 pages limit.
Proposals will be limited to 8 double-spaced pages with no less than 11-point font. Page limit excludes cover page, personnel qualifications, institutional letters, and ICMJE uniform disclosure forms, as well as budget and budget justification. Page limit includes project description with goals and objectives and a detailed proposal, as well as the projected timeline, anticipated challenges, and plan for human subjects protection.
Question: Could you please specify the differences between the signed cover letter from the institutional official supporting the submission and the institutional letter of support that attests to the availability of resources. If these are two different documents are there any templates available?
The Institutional Letter, which is signed by an official at the applicant organization, specifies that the organization 1) supports the application and 2) has available resources to effectively carry out the contract should they receive the award.
Question: Regarding conflict of interest, 3 years ago one of the team members was collaborating in a study funded by Amgen should this be reported as a COI?
An ICMJE uniform disclosure form for competing interests must be completed by all named persons on the research team and submitted with the RFP application. Disclosures should be made for all potential Conflicts of Interest over the past 36 months. The form can be accessed at www.icmje.org/coi_disclosure.pdf.
Question: I have a question regarding the RFP for rhbmp-2 . Is this exclusively targeting the use of this agent in spinal surgery or are you interested in its use (safety/efficacy) in any condition (for example, tibial fractures)? The RFP seems to focus on the spine (by mentioning complications specific to spine such as retrograde ejaculation); however, is not explicit or clear.
Yale University seeks proposals for the rigorous systematic review and meta-analysis of all available data from published and unpublished clinical trial program data, as well as post-market surveillance data collected through registries, cohort studies, or spontaneous case reports relating to available products containing recombinant human bone morphogenetic protein 2 (rhBMP-2) with a primary focus on its use for spinal indications, but also include studies assessing its use for non-spine indications.
Question: What is the background for Medtronic’s decision to let independent people scrutinize the data? Was it a threat from the FDA that unless this was done, the product might be withdrawn? And why did it come to Yale?
Medtronic, Inc. has provided a grant to Yale University to lead independent, systematic reviews of the safety and effectiveness of INFUSE®, Medtronic’s recombinant bone morphogenetic protein-2 (rhBMP-2) product. The grant also supports the dissemination of all Medtronic clinical research data on INFUSE® to investigators. The U.S. Food and Drug Administration played no role in requiring or suggesting that either Medtronic or Yale University engage in this research initiative.
Yale University submitted an unsolicited grant proposal to Medtronic to fund the research, appealing to Medtronic’s leadership to promote a more open and transparent research process and to allow the science that had been done examining INFUSE® to stand on its own. Dr. Krumholz proposed this project to Medtronic after articles published by The Spine Journal questioned the integrity of prior evaluations of rhBMP-2. He challenged the company to respond to the questions being raised about their research and rhBMP-2 by allowing their clinical trial program data to be re-evaluated by reputable research groups and committing to the process of independent evaluation and promotion of data sharing and transparency.
The leadership of the Yale Open Data Access project, Drs. Krumholz, Gross, and Ross, have worked for years to improve research conduct, with a particular focus on how industry marketing and promotion can undermine evidence-based clinical practice. Their work has described how a substantial portion of a company’s clinical trial program data is not available for research by independent scientists. There have been many examples of pharmaceutical products where safety questions were raised, but there was limited opportunity to use the complete data from the clinical trial program to address these concerns. These investigators have advocated for greater transparency of industry clinical research practice and urged companies to make their data available for independent analysis.
Question: Data from “17 clinical trials provided by Medtronic” will be delivered. How can we be sure that the company is not withholding data from less favourable trials? How do we know that these are ALL trials ever performed with the product?
Medtronic has provided written assurances that all data and information have been completely produced without redaction and that no documents and/or information have been withheld. This is both a legal obligation and a public declaration to their commitment to this research initiative.
Question: Will we get ALL information the company has on its trials? It is very important to see also the clinical study reports and the protocols, with amendments, if any, for the trials.
As a requirement for participation, Medtronic has agreed to provide all of the following to Yale University and are in the process of preparing the material, all of which will in turn be provided to the research groups and later made publicly available:
- All subject-level pre-market approval and post-market surveillance human subject clinical trial program data, as well as associated documentation, such as study protocols, statistical analysis plans, data definitions, and case report forms.
- All subject-level post-market surveillance data collected through registries or cohort studies on human subjects, as well as associated documentation.
- All spontaneous adverse event reports among human subjects received via the FDA or other means, as well as associated documentation.
- All documents submitted to the FDA or other federal regulatory agencies as part of new approval or indication applications.
- Written assurances that all data and information have been completely produced without redaction and that no documents and/or information have been withheld.
The Yale Open Data Access project distributed the Request for Proposals to at least 80 individuals and organizations. Due to the tight timescale of the Medtronic/Yale University Open Access Data Project, a widespread direct dissemination of the RFP was implemented, targeting groups across the world with experience in individual patient data meta-analysis. Individuals and organizations were identified through A) receipt of funding from the U.S. Agency of Healthcare Research and Quality Effective Health Care Program; B) contact with leading Cochrane investigators; C) enquiry via the UK Medical Research Council Individual Patient Data Meta-Analysis Group; and D) literature review among high-impact journals for similar work.
All applications meeting the requirements set forth within the request for proposals made by the Yale Open Data Access project will be reviewed.
Question: Why will two independent groups do the work instead of one, which, for the same amount of money, could do a more thorough job? Was this a condition Medtronic had for delivering the data and the money, or did Yale make this decision? My worry comes from my knowledge of “the doubt industry;” companies excel in saying that, as reports are conflicting, we still don’t know anything for sure, and two independent reviews are certain to disagree on a number of issues. A tobacco executive even said: “Doubt is our product.”
Yale University determined to have two independent research groups systematically review and meta-analyze the clinical data related to INFUSE® in order to promote reliability and independence in the evaluation of product data. Knowing that their work is being replicated by another’s will stimulate each group to pursue the evaluation with the utmost rigor and attention to detail. Full transparency regarding the methods and findings by each of the groups will provide further reassurance to the clinical and scientific community regarding the credibility of the work.
This Yale University/Medtronic research initiative has the possibility of establishing a landmark model for data transparency - a breakthrough in balancing the business needs for commercial success with the public health needs for independent review of all available human subject data for a drug, including clinical trial program data and post-market surveillance data. If successful, this can create a new standard of practice - and make it untenable for companies to hold back data on approved products in the future. Medtronic is taking an important leadership position here, establishing a more transparent and collaborative standard, that we hope others will follow.
To be clear, the initiative was completely designed by Yale University, with no input from Medtronic. Yale has taken several steps to ensure its independence from Medtronic for this initiative as well as to ensure the independence of the research groups contracted to perform the systematic review. First, Yale will not perform the systematic reviews but will facilitate their conduct by two organizations with international reputations for science and integrity. Yale will have control over the selection of these organizations but their reports will be published by them. The two groups will work independently to test the reliability of the analysis, and Yale will serve as an additional check. The reviews will be designed to provide full disclosure about the benefits and risks of the product, but are not seeking to deliver a verdict. The purpose is to present a comprehensive profile of the product - including the quality of the literature. Second, Dr. Ezekiel Emanuel, Chair of Bioethics at the U.S. National Institutes of Health, will chair an independent steering committee for this project. The committee will have 9-12 members, representing various areas of expertise in research conduct. Third, Dr. Kevin Bozic, Associate Professor and Vice Chair in the Department of Orthoapedic Surgery at University of California San Francisco, will chair a second independent steering committee of 5-6 members representing various areas of subject matter expertise.
Question: Yale might consider the option of some collaboration between the two selected research groups, e.g. the search for data will be labour-intensive and could be shared.
At this time, Yale University is requiring each selected research group to perform its systematic review independent of one another.
Question: Did Yale construct its organization, “THE YALE UNIVERSITY OPEN DATA ACCESS PROJECT, 2011” specifically for this purpose? Will it persist beyond the current project, enabling similar projects to be undertaken in future?
This is the first funded initiative taken on by the Yale University Open Data Access project. The goal of the Project is to create a new standard of practice, establishing a landmark model for data transparency that can be implemented with similar projects in the future.
Question: As long as the electronic proposal is received by YODAP by 11 pm EDT on Tuesday, September 27th, can the hard copy arrive a day or two after that? Or must the hard copy also be received by September 27th?
Electronic proposals must be submitted on Tuesday, September 27, 2011. Hardcopies should be postmarked no later than Wednesday, September 28, 2011.
Question: The RFP says: "A representative of the research team will be expected to attend a winter conference and present information about their work. Travel expenses will be paid for at least one researcher from each team." Does this mean that travel for one researcher will be paid separately and does not need to be included in the project budget? If we would like a second researcher to attend the conference, can we include that in the budget?
At least one representative of the research team will be expected to attend a winter conference and present information about their work. Travel expenses are allowable and should be budgeted for at least one researcher from each team.