VSDAttachment J5.docx

Attachment J.5

SAMPLE TASK ORDER # 3

SUBJECT TO AVAILABILITY OF FUNDS IN ACCORDANCE WITH FAR 52.232-18

TITLE OF PROJECT: Assessment of acute demyelinating events following vaccination

1. APPLICABILITY

This effort is within the scope of the basic contract discussed in 5.3 of the basic PWS

2. ORDER TYPE

The effort shall be proposed on a Cost-Plus-Fixed-Fee basis.

3. PERIOD OF PERFORMANCE

The period of performance is from the date of the contract award for twelve months.

4. PLACE OF PERFOMANCE

Services will be performed at vendor specified site in the United States.

5. BACKGROUND AND NEED

Acute demyelinating events following vaccination have been reported to occur following a number of vaccines, but the evidence regarding a causal association is limited. The events of interest include multiple sclerosis (MS), optic neuritis, acute disseminated encephalomyelitis (ADEM), and transverse myelitis. The recent Institute of Medicine report (2011), “Adverse effects of vaccines: evidence and causality”, has comprehensively reviewed scientific evidence from epidemiologic and biological mechanistic studies.1 For all of the specified acute demyelinating events, the report found inadequate evidence to either accept or reject a causal relationship. No significant association was found in studies on MS onsets in adults after MMR (also in children), influenza (also in children), hepatitis B, and diphtheria or tetanus toxoids or acellular pertussis antigen containing vaccines.1,2 ,3 These vaccines were also not associated with optic neuritis.1,3 In a recent systematic review of evidence, Farez & Correale4 also did not find any significant change in risk of developing MS after BCG, hepatitis B, influenza, MMR, and typhoid fever vaccinations. In fact, they found decreased risk associated with diphtheria and tetanus vaccinations.4 Similarly, there was no effect of vaccination (all the major vaccines included) on ADEM or transverse myelitis.1,5 However, most of these studies along with the IOM review identified substantial limitations with the studies that precluded a conclusive weighing of the evidence. These limitations included lack of validation for self-reported vaccination, selection bias, and confounding. This emphasizes the continued need for gathering evidence and research for public health protection and reassurance. The rarity of disease and the complex interplay between genetic, environmental, and microbial factors should be taken into account among other factors while designing vaccine safety studies and evaluating the effect of vaccination on demyelinating diseases.5,6

References

1. Institute of Medicine. Adverse effects of vaccines: evidence and causality. Washington DC: National Academies Press, 2011

2. Rutschmann OT, McCrory DC, Matchar DB. Immunization and MS: a summary of published evidence and recommendations. Immunization panel of the Multiple Sclerosis Council for Clinical Practice Guidelines. Neurology 2002; 59(12): 1837-43

3. Gout O. Vaccinations and multiple sclerosis. Neuological Science 2001; 22: 151-4

4. Farez MF, Correale J. Immunizations and risk of multiple sclerosis: systematic review and meta-analysis. J Neurol 2011; 258 (7): 1197-206

5. Agmon-Levin N, Kivity S, Szyper-Kravitz M, Shoenfeld Y. Transverse myelitits and vaccines: a multi-analysis. Lupus 2009; 18: 1198-1204

6. Vial T, Descotes J. Autoimmune diseases and vaccinations. Eur J Dermatol 2004; 14: 86-90

6. PROJECT OBJECTIVE

The purpose of this task order is to develop a protocol for a population-based study to evaluate the risk of acute demyelinating events (e.g., multiple sclerosis, optic neuritis, transverse myelitis, ADEM) associated with specified vaccines in different age groups (e.g., children and adults) and to implement this protocol through a single-site pilot study. The objectives also include revision of the protocol based on findings and lessons learned from the pilot study.

7. SCOPE OF WORK

This task order is for a contractor to develop, pilot, and revise a scientifically sound research protocol to evaluate the association between acute demyelinating events and vaccination. This research protocol should build upon existing scientific knowledge regarding the association between acute demyelinating diseases and vaccination and clearly demonstrate novel and innovative approaches in research design and methods through which high quality new scientific information could potentially be obtained. The design should incorporate approaches to overcome the limitations of prior research as identified by the 2011 IOM review. The study will utilize VSD data files, and other data collection methods as needed (e.g. personal interviews, collection of records from outside the VSD MCO), to identify potential incident cases and complete vaccination histories, as well as validation of case status. The contractor will conduct case validation. The protocol will be implemented at the contractor’s site as a pilot study. Work will include data collection at the contractor’s health plan and the conduct of analyses as described in the protocol. The aim of the pilot study will be to evaluate the protocol-specified procedures and instruments to identify needed modifications to improve study performance. Based on the findings from the pilot study, a revised protocol will be developed for a multi-site epidemiologic study that may be conducted through a subsequent task order.

8. TECHNICAL REQUIREMENTS

A. The contractor shall write a draft protocol to assess the association between acute demyelinating events and childhood and adult vaccinations

B. The draft protocol shall include type of study design as well as methods for identifying patient care visits (inpatient, Emergency Room, and outpatient) as far back at least as 2007 (with a preference to go back to 2000) that may represent acute, incident demyelinating events, selection of comparison subjects (if indicated), documentation of vaccines received and dates of vaccination, and information on covariables. Study years will be dependent on vaccine, outcome, and sample size requirements. For identifying potential cases, contractors should begin with the most recent year for which automated data are available and search back in automated data as far back as necessary to identify the required number of potential incident cases or as far back as automated data are available at the health plan.

C. The methods included in the protocol should utilize the VSD data files to the fullest extent possible. The protocol shall identify other electronic data sources to be used for this study and procedures for documenting vaccinations received outside the MCO setting.

D. The draft protocol shall specify methods of verification of case status and incidence date

E. The draft protocol shall describe the study design and include an analysis plan which will specify a comparison group (if needed), statistical analyses, and sample size and power.

F. The contractor shall develop data collection instruments for case validation and collection of vaccination and covariable information.

G. The contractor shall participate on conference calls to discuss study protocol and pilot study progress.

H. The contractor shall work closely with CDC in finalizing the draft protocol and seek CDC approval of the final draft of the protocol.

I. The contractor shall obtain IRB approval from their local institution to implement the study protocol in a pilot study

J. The contractor shall conduct a pilot study implementing the IRB approved study protocol. The pilot study will be a single-site study and will utilize the contractor’s health plan’s data only.

K. As part of the pilot study, the contractor shall test and evaluate all study procedures and instruments and make revisions as needed. The main objectives of the pilot study should focus on optimizing operational aspects of study conduct and methods for identifying potential cases (including potential number of cases identified), available data from computerized files and essential data elements that may require in-person or medical chart abstraction efforts (including outside the MCO), the development and evaluation of data collection instruments, and estimates of participation rates in various phases of the study.

L. A sample of charts may be selected for estimation of positive predictive value of ICD9 codes, availability of data to reasonably specify incidence date, and availability of vaccination data, as well as information on important potential confounders. (in-person interviews and methods to obtain vaccination records outside the contractor’s health plan may also have to be tested in the pilot study.)

M. The contractor shall keep CDC updated on a regular basis on study progress and barriers.

N. The contractor shall conduct all analyses associated with the study

O. The findings from the pilot study and work conducted for the study shall be reported to the government in the form of a final report.

P. Based on the lessons learned from conducting the single site pilot study, the contractor shall modify the protocol, if needed, so that it can be conducted as a multi-site VSD study. It is anticipated that the contractor would lead the full-scale multi-site study under a subsequent task order.

2. DELIVERABLES

E= Electronic copy only

Contractors shall propose delivery schedule and any additional deliverables that will enhance the contractor’s ability to manage and successfully complete the work and/or facilitate oversight by the COTR and VSD Project staff.

3. ADDITIONAL INSTRUCTIONS

Methodology and technical approach:

A. The Contractor should provide a narrative describing their technical understanding of the work. Describe the contractor’s understanding of main limitations of previous research on the topic and the contractor’s proposed methods to successfully overcome these limitations.

B. Describe proposed approach to develop the study protocol and conduct the pilot study, including:

1. Describe the approach the contractor will undertake to write the protocol

2. Describe the contractor’s ability to utilize SAS in order to write a program to extract the analytical files to create a study cohort from the VSD population. The contractor will utilize data files that follow the VSD data dictionary

3. Describe the methods in which the contractor will conduct case validation and how this will be performed. This includes both medical chart abstraction and interviews with potential cases and controls (if applicable)

4. Describe process for reconciliation of discrepancies of automated data and other non-electronic data sources that may occur during pilot study

5. Describe the ability to conduct statistical analysis including proposed methods that would be included in protocol