Orthopedic Registry Funding Opportunity Announcement

Questions and Answers

Highlights from Technical Assistance Call

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The following questions and answers were submitted during a technical assistance teleconference call that took place on August 17, 2009, from the Agency for Healthcare Research and Quality (AHRQ) on the Agency's funding opportunity announcement (FOA), RFA-HS-10-1008: AHRQ Developing Prospective Practice-based Comparative Effectiveness Research Clinical Registries: Orthopedic Devices, Drugs, and Procedures (P50). Select to access the FOA.

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Question: How many investigators are required in the application and what are their roles?

Answer: Only one principal investigator (PI) is allowed on the application at a minimum time commitment of 40 percent annually. The effort cannot be shared across more than one individual using the multiple PI format. The PI is the lead for the Research and Data Coordinating Center and assumes primary responsibility for overseeing the development and operation of the registry.

A lead co-investigator must be identified at each of at least five clinical centers or systems at a minimum effort of 25 percent annually per investigator. The PI may not serve as a lead co-investigator at one of the clinical centers.

The PI may designate additional individuals to lead other activities to best meet the needs of the registry.

Lead co-investigators for the proposed core research projects are not required to be different individuals from the clinical center leads or the PI unless desired by the PI.

All investigator roles must be defined and justified in the budget.

Question: Can an application that proposes a different program director (PD) or PI structure be reviewed and fully considered for funding, such as the Research and Data Coordinating Center being a sub award from a clinical center where the PD or PI is located?

Answer: The Funding Opportunity Announcement describes separate roles for the PI at 40 percent annual effort and clinical center lead total investigators at 25 percent annually.

The Research and Data Coordinating Center may be located at the same physical site as one of the clinical centers as long as a strong justification for this model is provided in the application.

Question: Must the research and data coordinating center be physically located at the PD or PI's institution?

Answer: The FOA requires that the PD or PI be the lead for the Research and Data Coordinating Center. So the application must provide a strong justification that this leadership can be accomplished effectively if the PI and the Research and Data Coordinating Center are at different physical locations.

Question: Is it possible for the percent effort for the lead PI and the clinical center lead co-investigators to be donated wholly or in part by the institution in a show of support, or must these amounts be included in the budget?

Answer: Investigator time can be donated by the institution. The percent investigator effort can be shown in the detailed budget request with an associated dollar value of zero. The value of this effort and institution contribution can be included in the text at the end of the budget justification section of the application.

Question: What are the required qualifications for the PI and clinical site co-investigator?

Answer: The reviewers will consider the expertise and experience of each investigator in any given application individually as well as the strength of the entire research team as a whole when scoring the application. The applicants are encouraged to document the proven leadership of the individual investigators and the research team in accomplishing complex clinical and research issues through collaborative effort across scientific disciplines and institutions. Such collaborative effort does not need to be limited to multicenter randomized controlled trials.

Question: What are the role and membership composition of the Registry Steering Committee, and how are the Registry Steering Committee chairperson and members selected?

Answer: The FOA states that the Registry Steering Committee is the governing body of the registry development. Included in its voting members are the program director or principal investigator of the Research and Data Coordinating Center, the lead co-investigators of at least five clinical centers, a patient representative, and a chairperson, who will advise the principal investigator on research activities and functions and conduct the Registry Steering Committee meetings.

The chairperson and members of the Registry Steering Committee are appointed upon grant award. Accordingly, the FOA is silent on the selection of the chairperson except to say that the individual must be a well-regarded researcher with no substantial financial conflict of interest. The FOA does not preclude any other scientifically qualified individuals, including the lead co-investigators of the clinical centers, from being appointed as the chairperson of the Registry Steering Committee so long as the optimal functioning of the Registry Steering Committee and the objectivity and impartiality of the chairperson are ensured.

The Registry Steering Committee will also include the AHRQ program official and representatives from the Centers for Medicare & Medicaid Services (CMS) and the Food and Drug Administration (FDA) as nonvoting ex officio members.

Question: Can investigators from for-profit or non-U.S. institutions participate in the application?

Answer: The FOA states that foreign institutions and for-profit organizations may participate as members of consortia or subcontractors only. Therefore, any member of the research team except the PI could be located at one of these institutions and participate through a subcontract or as a member of a consortium.

Question: Can one of the collaborating sites in the registry participate in more than one application?

Answer: The FOA is silent on the subject, and there is no explicit stipulation prohibiting collaborating sites from participating in more than one application. Only one award will be made under this FOA.

Question: Can the application include more than five participating sites, including community-based practices?

Answer: The FOA requires that the application must include at least five clinical centers, each with sufficient patients to support recruitment in a variety of studies in the registry. The FOA expects that individual clinical centers will vary in nature and experience, and thus may represent both different patient populations and unique expertise.

The designated clinical centers could be a medical center with existing relationships with private or community hospitals and physician practices or any network or consortium structure of community hospitals and practices with demonstrated clinical research excellence and a proven ability to recruit patients from various racial or ethnic groups.

As a whole, the registry will enroll eligible patients and assess clinical interventions on a broad range of diagnostics and therapeutics.

Question: Can you discuss "national" as it applies to a registry of five sites?

Answer: The application must describe the critical responsibilities of at least five clinical centers in recruitment of patients and data collection. It is expected that individual clinical centers will vary in nature and experience, and thus may represent both different patient populations and unique expertise. For example, the clinical centers could be geographically diverse major medical centers with existing relationships with private or community hospitals and physician practices.

The objective of the FOA is to encourage the broad representation and the inclusion of a substantial number of patient populations receiving implantable orthopedic devices and other related services.

Question: What is the research plan page limitation? The FOA stated 25 double-spaced pages, while the default requirements for the PHS 398 Form used for the P50 grant application is 25 single-spaced pages.

The correct research plan page limitation should read 25 single-spaced pages. We published a Notice of Correction, Number NOT-HS-09-010 on August 6, 2009, to inform the scientific community that we are amending the erroneous instructions that appeared in the original FOA. And we will include the specific URL to this notice in the transcript. [The URL is http://grants.nih.gov/grants/guide/notice-files/NOT-HS-09-010.html.]

Question: Should the three core projects be written as separate sections in the grant with their own specific aims, hypotheses, background and significance, preliminary studies, and research methods, or should these sections for the registry and core projects all be incorporated together under the same headings in the grant?

Answer: The FOA specifies a 25-page limit for the research plan. The general instructions on completing the PHS 398 also apply. Within those guidelines the PI can choose whatever format best presents the research plan.

Question: Is the primary goal of this request for applications (RFA) to create a national registry or to conduct comparative effectiveness research?

Answer: The purpose of this FOA is to develop a large, multicenter, preferably national orthopedic registry; to conduct rigorous clinical and scientific research with a primary focus on comparative effectiveness and safety research; and to develop scientific evidence regarding the short- and long-term benefits and harms of implantable orthopedic devices, drugs, and procedures. The two goals are complementary to one another.

Question: What should be the balance between a focus on comparative effectiveness vs. a focus on safety? And what type of safety research is AHRQ interested in from this registry?

Answer: Comparative effectiveness research is the conduct and synthesis of research comparing both the benefits and harms of different interventions and strategies to prevent, diagnose, treat, and monitor health conditions in real-world settings. Therefore, safety is included within the scope of comparative effectiveness. One goal of this registry initiative is to support the development of a sustainable data infrastructure and to conduct rigorous clinical and scientific research including comparative effectiveness and safety research. So some safety questions could be answered within the 4-year core research studies and others in the long term through the infrastructure created by the registry.

Question: Should this registry address orthopedic practice beyond total joint replacements? What about drugs, as mentioned in the title?

Answer: The initial focus of the registry effort should be to develop the necessary infrastructure for data collection and comparative effectiveness research activities, with concentration on hip and knee replacement. The FOA does not preclude study aims in other areas of orthopedic practice, provided hip and knee joint replacement devices and procedures also are included within the scope of the overall project.

The inclusion of drug data in the registry is an integral part of the comparative effectiveness research activities in ascertaining patient outcomes associated with joint replacement and other procedures.

Question: What outcomes is AHRQ most interested in studying within the 4-year timeframe of this FOA?

Answer: Some examples of the core research studies that would be responsive to the research plan requirements were included in the FOA. And those examples did include possible outcomes. However, the PI is free to choose the outcomes that best meet the aims of the research study proposed in the application.

Question: Does the FOA require a process for the collection of patient-reported outcomes?

Answer:The FOA states that the application should describe the willingness of all clinical centers in the study to collect all data elements across all study participants. Patient outcomes are no different from any other data element in that regard. It is expected that the applications describe the proposed data collection plans and infrastructure. The PI has flexibility in developing such plans to meet the goal. And such plans will be evaluated for responsiveness by the reviewers.

Question: Can you explain the relationship you expect with national specialty societies and Federal agencies established before the award and during the application preparation?

Answer: The FOA states the PI must hold preliminary discussions with relevant orthopedic specialty societies and other important stakeholders regarding any ongoing data standardization and transmission effort. Any discussions that help inform the proposed data collection plans and infrastructure may be useful prior to the award, but the PI has flexibility in developing plans to meet the goals of the FOA. Such plans will be evaluated for responsiveness by the reviewers.

Question: The FOA specifies collection of "all data from all patients." Genetic studies are often difficult to do with so many sites. Does this characterization of all data for all patients included genetic data?

Answer: Those types of data are certainly not precluded from study by the FOA. The clinical centers participating need to agree to that. And provided you adequately describe the study and it's adequately powered, those data can potentially be included in the research plan.

Question: As I read the FOA, it doesn't seem that it's necessary that every single center has to collect every single data point. If you go back to the goal of the project to develop an infrastructure that can be translatable into a national registry as well as do the core projects, that wouldn't be necessary in the research plan to accomplish that goal. Do you really expect, for example, if we have 15,000 patients a year, to collect all data points on all patients on all centers or just what we consider the minimum data set on all patients at all centers?

Answer: In terms of the FOA, there is certainly a set of data that we would like all clinical centers to agree on. But for the purposes of sub study, we would agree that there are additional data elements that could be added to meet the research aims for some additional study.

Question: To what extent is AHRQ interested in what happens to the patient before joint replacement surgery? For example, if there's a physical therapy program that may be beneficial both before and after surgery, would that fall under this FOA?

Answer: Yes, those types of things can be included. If you look under the section on clinical centers participating in the registry, there's a list of about nine examples of types of data that could be included. Rehabilitation is one example of the types of data that are listed in that section.

Question: This question is related to subcontracts from the primary. What guidance is there regarding subcontract budgets related to indirect costs and caps on salaries? Are there specific thresholds that were required, or preapproval from the agency?

Answer: There's no specification in the FOA with regard to percentage of facilities and administrative (F&A) costs allowed for the sub-recipients. In accordance with the HHS Grants Policy Statement, cost has to be reasonable, allocable, consistently applied, and in conformance with the terms and conditions of the award. This would also apply to sub-recipient cost as well.

Question: The 4-year timeframe is not very long term when it comes to typical complications of joint replacements. For example, for hips and knees, many of the complications seen are 5 and 10 years out from implantation.

So I have a two-part question to AHRQ. The FOA talks a lot about prospective studies. To get 5- and 10-year outcomes, we may need to combine retrospective with prospective studies. Is that permissible?

And second, if we are to do prospective studies that look 5 and 10 years out, some of these studies would of course be part of the sustainable registry you discussed. But the question is whether AHRQ envisions continued funding beyond the 4-year timeframe. Looking for 5-year outcomes would be impossible given the FOA as designed.

Answer: As far as combining prospective and retrospective data, that is certainly possible. As far as continuing funding, this is initial effort in the area, and we can't comment on whether there would be additional opportunities for funding in the longer term.

Question: Regarding the data confidentiality section of the plan, would there be any special protections for registry data from discoverability in the event of legal actions against device companies or payers or anything of that nature related to safety?

Answer: The AHRQ Web site contains a legal analysis offered to be of assistance to potential grant applicants on the confidentiality of sensitive data collected for the Agency for Healthcare Research and Quality (AHRQ) research projects: https://www.ahrq.gov/fund/datamemo.htm.

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Current as of August 2009