Vaccine Safety Research, Data Access, and Public

Trust

Findings and Recommendations from IOM

NVAC MeetingJune 8, 2005

Debra Lappin, J.D.Senior Advisor, B&D Sagamore, Public Health

and Life Sciences ConsultingMember, IOM Committee on the Review of NIP’s Research Procedures and Data Sharing Program

Background

• IOM Committee on the Review of the National Immunization Program’s (NIP) Research Procedures and Data Sharing Program

• Created at the request of NIP• Fast-track study

– Report was released within six months of first meeting

– Released on Feb. 17, 2005

Committee Membership

• Expertise in:– Epidemiology– Biostatistics– Research design– Research ethics– Vaccine research– Risk communication– Public input into the scientific process

Charge to the Committee

• Committee was tasked with examining two issues related to the Vaccine Safety Datalink (VSD)– 1. Review the design and the

implementation to date of the VSD Data Sharing Program to assess compliance with the current standards of practice for data sharing in the scientific community

Charge to the Committee (continued)

• 2. Review the iterative approaches to conducting analysis that are characteristics of studies using the complex, automated VSD system and review whether, when, and how preliminary findings about potential vaccine-related risks obtained from the VSD system should be shared with other scientists, communicated to the public, and used to make policy or recommendations to CDC.

• Recommendations to NIP and the National Center for Health Statistics (NCHS) for first task; Recommendations to NIP for second task

Overarching Principles

• Four overarching principles emerged from the committee’s recommendations:– Independence– Transparency– Fairness– Protection of confidentiality

Description of the VSD

• Created in 1991 • Collaborative effort of NIP and

several managed care organizations (MCOs)

• Large, linked database• Administrative records from 7

million members of 8 MCOs• Valuable tool for vaccine safety

research

VSD Data Sharing Program

• Throughout first decade of the VSD’s existence, only researchers affiliated (or collaborating) with NIP or the participating MCOs could access VSD data

• In 2000, independent external researchers requested access to VSD data

• VSD data sharing program created in August 2002

VSD Data Sharing Program (continued)

• Data sharing program guidelines have undergone multiple revisions since first created

• Organizational responsibility for the VSD data sharing program transferred from NIP to NCHS in March 2004

• Access to VSD data provided at NCHS’s Research Data Center

VSD Data Sharing Program (continued)

• Independent external researchers currently can submit applications to do:– New studies– Reanalyses of published studies

• Only one group of researchers has accessed VSD data through the data sharing program

• The new VSD contract (which took effect Sept. 2002) restricted the data that could be made available through the data sharing program

Limitations of the VSD Data Sharing Program

• Independent external researchers only allowed access to:– Automated VSD data– Data from before 2001, for new studies

• Researchers affiliated with NIP or the participating MCOs – Can obtain chart-review-verified data– Allowed access to all years of VSD data

Limitations of the VSD Data Sharing Program (continued)

• For new studies, independent external researchers need to collaborate with researchers affiliated with NIP or the MCOs to gain access to all years of VSD data or chart-review verified data– There may not be a willing collaborator

• For reanalyses, independent external researchers only allowed access to final datasets

Some Committee Recommendations Related to

Data Sharing Program• NIP should require the designation of a

facilitator for collaboration at each MCO as a condition of the VSD contract (Rec. 3.3)

• For reanalyses, independent external researchers should be allowed access to earlier versions of datasets (Rec. 3.4)

• NIP and the VSD contractor should evaluate the feasibility of streamlining the IRB review process for reanalyses (Rec. 3.10)

Release of Preliminary Findings Based on VSD Data

• Controversy associated with a thimerosal screening study that used VSD data

• Reasons offered for some people’s criticisms of the study:– Changes in the original study protocol– Changes in eligibility criteria– Selective official release of preliminary findings– Inclusion of vaccine-manufacturer

representatives in an expert review meeting about the study

Some Committee Recommendations Related to Release of Preliminary

Findings• In nearly all situations, preliminary findings from

VSD data should be subject to independent external peer review before being communicated to the public or used as the basis of a policy decision (Rec. 4.6)

• Preliminary findings from VSD data should be shared with the public whenever the findings are presented to anyone other than collaborators in the research, federal employees responsible for research activities, MCO-affiliated VSD researchers, scientific journals, peer reviewers, and people responsible for oversight of the research (Rec. 4.7)

Some Committee Recommendations Related to Release of Preliminary

Findings• Preliminary findings from VSD data

should be shared with the public whenever these findings contribute to the basis of a policy decision or are used to change guidelines on vaccine administration (Rec. 4.8)

• When final results from VSD analyses or studies are released through publication or presentation at a meeting, preliminary findings should be shared only rarely (Rec. 4.9)

VSD Research Plan

• The VSD is the only population-based resource in the U.S. that has sufficient sample size to study certain rare vaccine adverse events

• Significant federal resources are dedicated to the VSD (~$13 million in FY 2004)

• So far, there have been few opportunities for the public to have direct input into VSD research priorities and allocation of resources

VSD Research Plan (continued)

• The committee recommended that NIP develop an annual research plan (Rec. 4.1)– The plan should define priorities for new studies– The plan should be made public– Material deviations from the plan should be

identified and be publicly available• The annual VSD research plan should be

developed with broad input from interested parties

• The public should be involved in establishing priorities for research

Independent Review of VSD Activities

• Some members of the public have concerns about:– the independence and fairness of the review

of VSD data sharing proposals– determinations about when and how to

release preliminary findings of VSD analyses

Independent Review of VSD Activities (continued)

• A perception of bias in the process used to review data sharing proposals or in the priorities established for the VSD research plan could jeopardize public confidence in VSD activities

• A lack of transparency of these processes could affect public trust in the use of the VSD to draw scientific conclusions about vaccine safety

Independent Review of VSD Activities (continued)

• To address some of these concerns, the committee recommended that two independent groups advise on different aspects of the VSD program:– A subcommittee of NVAC to review and

provide advice on the VSD research plan annually

– An independent review committee to review research proposals and provide advice on when preliminary findings from VSD data should be shared with the public

Use of an NVAC Subcommittee

• How priorities for the VSD research plan are set and how much input is sought from stakeholders outside the VSD steering committee are unclear

• The limitations of the VSD data sharing program and the concomitant limited ability of independent external researchers to conduct high-quality new studies create a special need to involve the public in the priority-setting process for the VSD research plan

Use of an NVAC Subcommittee (continued)

• Because of limitations with the data sharing program, independent external researchers may not be able to conduct studies that members of the public consider high priority

• Stakeholders need to have an opportunity to provide input into the VSD research priority-setting process

• The process should be as transparent as possible

Committee Recommendations about

NVAC Subcommittee• A subcommittee of NVAC that includes

representatives of a wide variety of stakeholders should review and provide advice annually to the NIP on the VSD research plan (Rec. 5.1)– The subcommittee charged with this role could be the

existing Subcommittee on Safety and Communications or a subcommittee created specifically for this purpose

• By utilizing a subcommittee of NVAC, regular voting members of NVAC, nonvoting ex officio members (e.g., CDC, FDA, other federal agencies), and nonvoting liaison representatives (e.g., a representative of America’s Health Insurance Plans) can provide input on priorities for VSD research

Committee Recommendations about

NVAC Subcommittee• NIP should propose to the National

Vaccine Program that additional liaison representatives be appointed to the NVAC subcommittee to ensure that all perspectives are heard (Rec. 5.2)– Important to adequately represent advocacy

groups and other members of the public at meetings addressing the VSD research plan

Use of an Independent Review Committee

• Independence, transparency, and fairness must characterize VSD research activities if the public is to trust findings and conclusions based on VSD data– The extent to which there is oversight of

NIP-affiliated and MCO-affiliated researchers’ adherence to their research protocols is unclear to the public

Use of an Independent Review Committee

(continued)• When decisions about the release of

preliminary findings do not fit neatly within one of the categories described earlier, advice of an independent committee may be needed– Such a committee can evaluate the public’s

right to know compared with the possibility of alarming the public about a risk that might not exist

Committee Recommendation about Independent Review

Committee• An independent review committee with

minimal and balanced biases and conflicts of interest should be created to (Rec. 5.3):– Review independent external researchers’

proposals to use VSD data through the data sharing program

– Review research proposals from internal researchers and provide oversight of changes in or deviations from research protocols for internal VSD studies

– Provide advice on when and how preliminary VSD findings should be made public

For additional information about the committee or the

report, please contact:

• Study Director: Andrea Pernack Anason• Phone: 202-334-2344• E-mail: nipdatasharing@nas.edu• Website: http://www.iom.edu/nipdatasharing