VSD.SampleTaskOrder 2.doc.docx

Attachment D

SAMPLE TASK ORDER # 2

TITLE OF PROJECT: Population-Based Evaluation of Anaphylaxis and Severe Allergic Reactions 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 contractor’s specified site in the United States.

5. BACKGROUND AND NEED

Vaccines, like all other drugs, have the potential to cause allergic reactions. Acute, severe allergic reactions to vaccines are infrequent, and seldom life threatening. However, the only contraindication applicable to all vaccines is a history of a severe allergic reaction (i.e., anaphylaxis) after a previous dose of vaccine or to a vaccine component (unless the recipient has been desensitized). Components that may be allergenic include the vaccine antigen(s), including proteins, carbohydrates, and complex conjugates, and additional components, such as adjuvants, preservatives, and residuals from the manufacturing process (preservatives, stabilizers, and residual media used in preparation of the vaccine). Individual vaccine components that have been implicated in acute vaccine reactions include egg protein, gelatin, and potentially other additives.

Although anaphylactic reactions are rare after vaccination, their immediate onset and life-threatening nature require that all personnel and facilities providing vaccinations have procedures in place for anaphylaxis management.1. Virtually all vaccines have the potential to trigger anaphylaxis. Anaphylaxis usually occurs within minutes of vaccine administration and rapid recognition and initiation of treatment with epinephrine is required to prevent possible progression to cardiovascular collapse. Anaphylaxis may be under-diagnosed even when the patient is seen in an emergency facility, particularly if it is the patient’s first episode, if the trigger is unknown/previously unrecognized, or if symptoms are mild or transient (or masked by first aid administration of epinephrine [EpiPen]). Also, the discharge diagnosis may only indicate an acute allergic or hypersensitivity reaction. Failure to diagnose anaphylaxis may result in inappropriate therapy (as a mild allergic reaction) in patients putting them at risk of life-threatening anaphylaxis after a second exposure to the same allergic trigger. Recently, the worldwide prevalence of allergy, especially IgE mediated atopic diseases, has increased dramatically and gender and age differences have been elucidated.2 However, despite advances in understanding the pathogenesis of anaphylaxis, risk assessment of individuals with anaphylaxis is hampered by lack of an optimal and readily available laboratory test to confirm the diagnosis and to identify allergen sensitized individuals who are increased risk of anaphylaxis.

The VSD project has published two key studies on anaphylaxis in children and adolescents following vaccination during 1991-1997 (Bohlke);3, 4 one of these reported that vaccine –associated anaphylaxis is extremely rare, with only 5 cases identified after administration of 7,644,049 vaccine doses (a risk of 0.65 cases per million doses). Since these published reports, there have been changes to the recommended child and adult immunization schedules with the introduction of several new vaccines/vaccine combinations. In 2007, the Brighton Collaboration published a standardized case definition for anaphylaxis following vaccinations.5 With a standardized definition for anaphylaxis as well as with additional vaccines included in the vaccination schedule; an updated rate of confirmed anaphylaxis and allergic reactions is needed.

References

1.CDC MMWR General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). 2011; 60:1-58.

2. Simons FE, Ardusso LRF, Bilo B, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. J Allergy Clin Immunol 2011; 127:593.e1-e22.

3. Bohlke K Davis RL, Marcy M, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003; 112:815-820.

4. Bohlke K, Davis RL, DeStefano F, et al. Vaccine Safety Datalink Team. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization. J Allergy Clin Immunol 2004; 43: 536-542.

5. Ruggeberg JU, Gold MS, Bayas JM, et al and The Brighton Collaboration Anaphylaxis Working Group. Anaphylaxis: Case definition and guidelines for data collection, analysis and presentation of immunization safety data. Vaccine 2007; 25:5675-5684.

6. PROJECT OBJECTIVE

The purpose of this project is to estimate the incidence rate and describe anaphylaxis and severe allergic reactions following vaccination.

7. SCOPE OF WORK

This task order is for the contractor in the VSD to participate and contribute automated electronic data as well as chart review data to the CDC in order for CDC to lead a population based evaluation of the incidence of anaphylaxis and severe allergic reactions following vaccination among all age groups, including children and adults.

8. TECHNICAL REQUIREMENTS

Working closely and collaboratively with CDC, the contractor shall accomplish the following:

A. Serve as a participating site on this study

B. Provide comments to the study protocol and the chart review instrument (see attached draft).

C. Seek IRB approval and DUA execution if needed for protocol

D. Allow CDC access to available VSD data files through the DDM in order to obtain results from programs

E. Allow CDC to run SAS programs created by the CDC, using a distributed data model (DDM) to establish a study population, in order to identify potential cases and provide descriptive statistics. Cases will be identified utilizing administrative/computerized data files and data linkages from outpatient, inpatient, and emergency room settings. Individual level data will be transferred to CDC in a SAS dataset thru the DDM.

F. Review and approve SAS DDM programs written by CDC. Multiple versions of the programs may need to be reviewed.

G. Correct any errors in the VSD Cycle/DDF data found through data quality checks related to the study

H. Participate on a medical chart abstraction training via conference call to understand medical chart abstraction process

I. Conduct chart review on potential cases identified through SAS programs for case validation

J. Participate on conference calls regarding the study

K. Ensure that the medical record data is linkable to the administrative/computerized data.

L. Provide additional automated information as an alternative to limit chart review for future studies

M. Provide a copy of completed chart abstraction forms and other documentation for the medical record to CDC.

N. Identify at least one individual who will take responsibility for the integrity of data contributed to the study and may be a co-author on a peer-reviewed publication of the study. The identified person will review and provide comments on CDC led manuscript.

9. Deliverables In order to verify deliverables relating to the creation of the DDM and the associated files, the CDC will run a SAS program to ensure that files are created and available for use.

Within 90days of contract award

On an as needed frequency. Response to government will be within 7 days of receipt of CDC program placed on contractor’s server

1 to PO (E) At the end of each quarter, after contract has been award

E= electronic version only P= paper version only

Contractors shall propose a 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.

10. SPECIFIC TASK ORDER INSTRUCTIONS (to be included as part of technical proposal response in Volume 2)

Methodology and technical approach.

The Contractor should provide a narrative describing their technical understanding of the work and describing their internal capabilities:

A. Description of IRB and DUA processes for this study

B. Describe the type of data that can be collected for this study and any limitations (i.e. specific data that might not be allowed to be transferred to CD or be contained in the analytic datafile (e.g. specific dates or individual level data)

C. Describe the process of reviewing and approving the SAS programs that will be utilized for necessary data extraction.

D. Describe population in which medical record abstraction is available (as compared to total population)

E. Description of how medical records will be abstracted at each medical setting (inpatient, outpatient, and ER). If any hospitals are not owned by health plan, describe the process in which medical records can be abstracted. Outline methods used for accessing charts for members who had an out-of network episode. Indicate the timeliness of completing the chart abstraction form for each scenario.

F. Describe the process of ensuring ensure data quality of medical record abstraction.

Draft VSD Sample Protocol

Risk of anaphylaxis following vaccination in children and adults

Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention

Investigators

(CDC)

(VSD sites) VSD site investigators

List of Acronyms

Summary

This is a study to be conducted within the Vaccine Safety Datalink (VSD) project. It will build upon the results of a previous VSD study which examined the risk of anaphylaxis following vaccination in children. The study will assess the risk of anaphylaxis among children, adolescents and adults following US licensed vaccines. Since the earlier published report, there have been changes to the recommended child and adult immunization schedules with the introduction of several new vaccines/vaccine combinations. In 2007, the Brighton Collaboration published a standardized case definition for anaphylaxis following vaccinations. With a standardized definition for anaphylaxis as well as with additional vaccines included in the vaccination schedule, an updated rate of confirmed anaphylaxis and allergic reactions is needed. This study will require individual level data (e.g., date of birth, date of vaccination, date of healthcare visit) and review of medical records.

1. Background

1.1. The Vaccine Safety Datalink

The Vaccine Safety Datalink (VSD) project was created by the Centers for Disease Control and Prevention (CDC) in 1990 to conduct post-marketing evaluations of vaccine safety. VSD is part of the CDC’s Immunization Safety Office and serves as the primary mechanism for population-based evaluations of vaccine safety in the United States. Historically, the VSD has been a collaboration between CDC and several managed care organizations (MCO). As described by Baggs, et al, in ‘The Vaccine Safety Datalink: A Model for Monitoring Immunization Safety’, “Since inception of the VSD, each MCO has prepared annual data files, called cycle files, that contain member information obtained from administrative files maintained by the individual MCOs. The cycle files include demographic and medical services information on their members, such as age and gender, health plan enrollment, vaccinations, hospitalizations, outpatient clinic visits, emergency department visits, urgent care visits, mortality data, and additional birth information (e.g., birth weight) when available. To ensure confidentiality and comply with federal regulations, each person within the VSD is assigned a unique, randomized VSD study identification number that is not linked to their MCO member identification number (however, the site is responsible for maintaining the linkage which will not be shared with CDC). VSD study identification numbers can be used to link data on demographics and medical services. A standardized data dictionary, which ensures data consistency across sites, is updated each year by the CDC and the VSD MCOs.”1 Since 2005, most VSD data files are updated weekly. Each MCO is able to link the VSD study identification number to personal identifiers for its health plan members only. This link cannot be made by CDC or the other MCOs.

1.2. Anaphylaxis and Vaccinations

Anaphylaxis is an acute severe and potentially lethal, generalized or systemic hypersensitivity reaction that occurs with simultaneous involvement of two or more organ systems (mucocutaneous, respiratory, cardiovascular, gastrointestinal and/or neurologic signs and symptoms). Signs and symptoms generally develop within minutes to a few hours after exposure to a precipitating factor.2 Common triggers of anaphylaxis include food, drugs (rarely including vaccines) and venom,3,4 as well as latex2 and exercise.3 Death, if it occurs, usually results from airway obstruction caused by laryngeal edema or bronchospasm and may be associated with cardiovascular collapse. Other significant clinical signs and symptoms may include: cyanosis, hypotension, bradycardia, tachycardia, arrhythmia, edema of the pharynx and/or trachea and/or larynx with stridor and dyspnea. Anaphylaxis does not produce pathognomonic post-mortem findings.

Case definition of anaphylaxis varies across previously published reports, but most utilize a combination of symptoms and, in some cases, treatment. The diagnosis is considered to be highly likely when one of three clinical criteria is met: (1) acute onset of an illness with involvement of the skin, mucosal tissue, or both AND respiratory compromise and/or hypotension; (2) exposure to a likely antigen AND rapid development of two or more skin-mucosal involvement, respiratory compromise, hypotension, or persistent GI symptoms; or (3) exposure to a known allergen and rapid development of hypotension. 5 Cutaneous involvement-mainly angioneurotic edema (angioedema) or urticarial (hives) is the most frequent manifestation of anaphylaxis (reported in 80-90% episodes), 6 other manifestations may include respiratory tract involvement (up to 70% of cases), gastrointestinal tract involvement (45%), and central nervous system involvement (15%). 6,7 Laboratory tests for serum tryptase, plasma or urine histamine may help establish the diagnosis of anaphylaxis.6 The lifetime prevalence of anaphylaxis from all triggers is estimated to range from 0.05% to 2.0%, with the largest number of incident cases occurring in children and adolescents. 8 Epinephrine is universally recommended as the primary treatment for acute anaphylaxis, and can be administered SQ, IM or IV; however, IV route is only indicated in cases of severe hypotension, cardiovascular arrest, or failure to respond after administration by other routes. 6,7

A study from the Vaccine Safety Datalink (VSD) published in 2003 quantified the risk of anaphylaxis following vaccination in children and adolescents.13 This study used an algorithm (Bohlke algorithm) to identify anaphylaxis cases (see below). The calculated incidence rate from this study (0.65 cases per million doses) has been used as reference for other vaccine related safety studies and investigations, however this study used data from 1991-1997. Since these published reports, there have been changes to the recommended child and adult immunization schedules with the introduction of several new vaccines/vaccine combinations. In 2007, the Brighton Collaboration published a standardized case definition for anaphylaxis following vaccinations.14 With a standardized definition for anaphylaxis as well as with additional vaccines included in the vaccination schedule, an updated rate of confirmed anaphylaxis and allergic reactions is needed. Recently, a committee of the Institute of Medicine (IOM) concluded that epidemiologic and mechanistic evidence convincingly supports a causal relationship for anaphylaxis and several vaccines (MMR, varicella, influenza, hepatitis B, DT- and TT- and aP-containing, meningococcal), favors acceptance of a causal relationship for the HPV (mechanistic evidence only) and was inadequate for hepatitis A vaccine.15 The life-threatening nature of anaphylaxis and the acceptance of a causal relationship with certain vaccines make estimation of the magnitude of the risk following vaccination an important priority for vaccine-safety research. However, given the infrequency with which anaphylaxis occurs large study populations are necessary to study this exposure-disease relationship. The VSD project offers such a population and has conducted similar studies of rare vaccine safety outcomes by preliminary screening for potential cases using the automated database which is then supplemented by medical record confirmation.

2. Objectives

2.1 To estimate the incidence rate of anaphylaxis following all vaccines (and if there are sufficient numbers by separate vaccine type) in the VSD population vaccinated between January 1, 2005 and December 31, 2011.

2.2 To assess the extent to which ICD-9-CM codes represent true cases of anaphylaxis and the proportion of cases identified by ICD-9-CM code that are chart confirmed by each setting ER, outpatient clinic, and hospital inpatient

2.3 To describe the confirmed cases of anaphylaxis (age and sex, symptoms, treatment, time interval between exposure and onset of symptoms, and setting in which the episode occurred and the person was treated). Also, if there is evidence of under-coding of anaphylaxis, whether it is possible to distinguish anaphylaxis cases diagnosed as other allergic reactions from anaphylaxis cases diagnosed as anaphylaxis. The use of procedure codes or concomitant diagnoses to identify true cases of anaphylaxis using only automated data will also be explored.

2.4 To compare the relative performance of the Bohlke algorithm13 and the Brighton Collaboration (BC) criteria14 in identifying anaphylaxis cases.

3. Methods

3.1. Study Population

All children and adults enrolled in participating sites’ automated databases with a vaccination record during the specified period will be included in the study population.

3.2. Study Period

January 1, 2005 to December 31, 2011

3.3. Outcome-Anaphylaxis

3.3.1. Case Finding

Case finding will initially involve screening automated data for all ICD-9-CM codes for outpatient and emergency department visits and inpatient/hospitalizations specific for anaphylaxis following vaccination. The ICD-9-CM codes specific for anaphylaxis are: 995.0, anaphylactic shock; 995.6 anaphylactic shock due to adverse food reaction; 999.4, anaphylactic shock caused by serum; and 995.4 shock due to anesthesia, E948.0 through E948.9 (any adverse reaction from bacterial vaccines), and E949.0 through E949.9 (any adverse reaction from other vaccines and biological substances).

Since previous studies have suggested that some anaphylaxis cases are coded as other allergic reactions, a secondary screen of the automated data will be conducted to identify all vaccine-exposed persons with severe allergic episodes (restricted to diagnoses occurring on day 0). The ICD-9-CM codes included are 708.0 (allergic urticaria), 708.9 (urticaria NOS), 995.1 (angioneurotic edema), 995.2 (unspecified adverse effect of drug), 995.3 (allergy, unspecified), and 695.1 (erythema multiforme). Algorithms that supplement these less specific ICD-9-CM codes will be explored to try to improve the specificity of the codes (e.g., pharmacy codes indicating administration of epinephrine or other drugs commonly used to treat anaphylaxis).

3.3.2. Medical Chart Review

Medical chart review will be conducted by individual VSD participating sites on all potential anaphylaxis cases identified by the initial automated data screen using a standardized chart abstraction tool (see attached). The purpose is to obtain additional clinical information to document a clinical diagnosis of anaphylaxis including whether the diagnosis was recorded in the chart by the treating provider. To enable direct comparison with the results of the published VSD study this medical chart review will be restricted to diagnoses occurring on days 0 to 2 after vaccination (day 0 defined as the same day as vaccination) for the specific anaphylaxis ICD-9-CM code 995.0 and day 0 for ICD-9 codes E948.0 through E948.9 and E949.0 through E949.9. Initially and to the extent possible, both the Bohlke algorithm and Brighton Collaboration criteria will be applied to every potential anaphylaxis case identified by the specified anaphylaxis ICD-9-CM codes. Depending on available medical record data, however, one of the criteria or some modification of the two may be determined to be more suitable for purposes of this study. Initially, medical chart abstractions will also be performed on a random sample of vaccine-exposed persons identified by the secondary screen of the automated data with selected allergic episodes (codes as specified above). If a de novo algorithm that uses supplemental electronic data along with the secondary screening codes can be developed, all potential cases identified using this algorithm will also be chart abstracted. All chart abstraction forms will be sent to CDC in hard copy.

3.3.3. Case Validation

All completed chart abstraction forms will be reviewed by a CDC medical officer and the Brighton Collaboration (BC) criteria (level 1, 2, 3; definite, probable, possible) for anaphylaxis will be applied (see attached). A physician’s written diagnosis of anaphylaxis in the chart will be sufficient to confirm the diagnosis if there is not enough information to meet the criteria. To enable direct comparison with the results of the published VSD study,13 the Bohlke algorithm (based on case’s symptoms, timeframe from exposure to symptom onset, treatment and if applicable a physician’s diagnosis) will be used to identify probable and possible anaphylaxis cases (see attached). Per the algorithm, at least two of the following will be required based on chart review to establish a diagnosis of anaphylaxis: mucocutaneous, respiratory, cardiovascular or gastrointestinal (GI) symptoms. One difference between the BC criteria and the algorithm is in the significance placed upon GI symptoms. Neurologic symptoms may be present with anaphylaxis, but occur less frequently than the other symptoms; however, we will collect information about the complete constellation of symptoms. Time interval between exposure and symptoms will also be considered. Although the BC criteria specify a “sudden onset and rapid progression” of signs and symptoms of anaphylaxis, an exact timeframe is not specified. Per the algorithm, if the interval is long (>4 hours) or unknown, medical treatment suggestive of anaphylaxis will be required to confirm the diagnosis. Anaphylactoid reactions, which are not IgE mediated, are clinically indistinguishable from anaphylaxis will be included as anaphylaxis.13,14 Information about the cause of anaphylaxis (e.g., egg allergy, medication allergy) will also be collected by chart review in order to describe more fully our case series.

3.4. Exposures

Vaccines will be classified according to the HL7 Table 0292 vaccine administered standard code set. Vaccine exposure will be defined using the automated data. Review of medical records will be undertaken for all cases identified with ICD-9 codes for anaphylaxis and a sampling of cases with other related allergy diagnoses to confirm the diagnosis (see below) and to determine if the anaphylaxis event occurred after the vaccination.

3.5. Other Variables

Other variables that will be collected from the electronic records are sex, date of birth, VSD site and MCO enrollment dates. The incidence of anaphylaxis has previously been shown to vary with age.8 Other ICD-9-CM codes listed on the date of the outcome will also be collected to determine if patients had conditions or were using medications that could have contributed to the anaphylaxis or severe allergic outcome diagnosis. In addition, medical chart abstraction will specifically inquire for any past history of anaphylaxis, asthma, atopic dermatitis, allergic bronchitis, rhinitis, bronchiolitis and specific allergies (e.g., to egg or medications). The dose number of a vaccine in a series will be calculated in order to assess dose specific effects on the risk of anaphylaxis. Seasonality of the outcome will be assessed by evaluating the date of outcome by time periods such as quarter and month.

3.6. Analyses

For this cohort study, we anticipate treating the outcome as a dichotomous variable, i.e., an individual either did or did not have anaphylaxis during the study period. We will ascertain the number of visits with the code for each outcome per person in the automated data. This data will be used for descriptive purposes, and if multiple occurrences of the outcome per person occurred during the study period, secondary analysis will be performed taking into account multiple events per person. The main objective will be to calculate rates of anaphylaxis following each vaccine type and following all vaccination events combined (where a vaccination event represents any occasion when one or more vaccines were administered to an individual.) Analysis will be done using modeling and will stratify for age, sex, VSD site, and seasonality.

4. Human Subjects Protection

This protocol will require IRB approval as required by each individual VSD site. Data use agreements will be signed with participating sites as needed. CDC staff will help coordinate obtaining IRB approvals and data use agreements (where applicable) from each site.

5. Privacy and Confidentiality Provisions

The privacy and confidentiality of all study subjects will be strictly protected according to standard VSD procedures. This study will utilize a limited data set containing individual level records of protected health information (PHI). The personal identifiers to be included are elements of dates that include date of birth and dates of health care visits. Information associated with each health care visit date will include the type of visit (inpatient or outpatient), the medical diagnoses recorded for the visit, and receipt of vaccines during the visit.

6. Data Security

Data required for this study will be transferred from the VSD sites to CDC using two secure methods known as the ‘indirect’ and ‘direct’ methods. The indirect method uses a secure server known as the ‘hub’, to which sites and CDC researchers send SAS computer programs and on which data files are stored. Each site can retrieve and use its own SAS programs but cannot access programs or information that belongs to other sites. Each site sends its SAS logs, output, and analytical data subsets back to the hub for retrieval by CDC researchers. The direct method allows CDC researchers to submit SAS programs interactively through a secure SAS remote session using SAS Connect, an internet communication protocol. All data transfers are conducted securely by using encrypted methods. CDC computer accounts used to access the data are password protected. CDC investigators and data managers employed by the Immunization Safety Office to work on the VSD will be the only individuals with access to the data. VSD site personnel will complete chart abstraction forms and send hard copies to CDC for review, adjudication and merging into an analytic database.

7. VSD Site Responsibilities

CDC will oversee the conduct of the study and have primary responsibility for obtaining IRB review, analysis of data, interpretation of results, and preparation of reports for presentation or publication. CDC programmers will write and test SAS programs to extract electronic data using the distributed data model (DDM) from standard VSD files. Those files that are used to produce the final results will be saved. The data set to be analyzed and stored at CDC will consist of individual records for each person in the study cohort. CDC staff will not perform medical record abstraction. Medical chart abstraction will be performed by staff at VSD sites and may require considerable chart abstraction resources. VSD site investigators may participate in interpretation of results and preparation of reports. Participating VSD sites will be responsible for obtaining IRB review in accordance with their institution’s procedures. The study will use automated data and chart validation. Participating sites are responsible for site specific IRB approvals and data use agreements when applicable. Sites will be invited to provide feedback on the draft protocol and manuscript as they develop. Since the study uses only standard cycle data and will use the DDM to obtain data extractions, none to very minimal programming resources would be required from the sites.

8. Data Management

CDC will oversee study documentation and archival. All project related electronic documents, data sets, and files will be stored on CDC computers, which have restricted access. Data exchange will use methods that will assure security, primarily through the VSD DDM. The archive will include updated study protocol, SAS programs, IRB documents, SAS output, analytical data sets, and manuscripts; it will clearly identify and permanently save those files.

9. Timeline

10. References

1. Baggs J, Gee J, Lewis E, Fowler G, Benson P, Lieu T, et al. The Vaccine Safety Datalink: A model for monitoring vaccine safety. Pediatrics 2011; 127:S45-S53.

2. Austen KF. Disease of immediate type hypersensitivity. In: Harrison’s Principles of Internal Medicine, 13th edition. Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL (eds). McGraw-Hill, New York, 1994: 1630-38.

3. Dibs SD, Baker MD. Anaphylaxis in children: a 5-year experience. Pediatrics 1997;99(1):E7.

4. Novembre E, Cianferoni A, Bernardini R, Mugnaini L, Caffarelli C, Cavagni G, Giovane A, Vierucci A. Anaphylaxis in children: clinical and allergologic features. Pediatrics 1998;101(4):E8.

5. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and a management of anaphylaxis: summary report-Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis network symposium. J Allerggy Clin Immunol 2006; 117:391-397.

6. Lieberman P, Nicklas RA, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter. 2010 update. J Allergy Clin Immunol 2010; 126:477-480, e471-442.

7. Simmons FE. Anaphylaxis. J Allergy Immunol 2010; 125:S161-181.

8. Lieberman P, Carmago CA, Jr., Bohlke K, et al. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol 2006; 97:596-602.

9. Institute of Medicine. Adverse events associated with childhood vaccines: evidence bearing on causality. Stratton KR, Howe CJ, Johnston RB (eds). National Academy Press, Washington DC, 1994.

10. CDC MMWR General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). 2011; 60:1-58.

11. Simons FE, Ardusso LRF, Bilo B, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. J Allergy Clin Immunol 2011; 127:593.e1-e22.

12. Simons FE. Anaphylaxis: recent advances in assessment and treatment. J Allergy Clin Immunol 2009; 124:625-636.

13. Bohlke K Davis RL, Marcy M, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003; 112:815-820.

14. Ruggeberg JU, Gold MS, Bayas JM, et al and The Brighton Collaboration Anaphylaxis Working Group. Anaphylaxis: Case definition and guidelines for data collection, analysis and presentation of immunization safety data. Vaccine 2007; 25:5675-5684.

15. Stratton K, Ford A, Rusch E, Clayton EW (eds). Adverse effects of vaccines: evidence and causality. Institute of Medicine. 2011 National Academies Press, Washington DC.

11. Anaphylaxis Chart Abstraction Form

VSD ANAPHYLAXIS STUDY

ANAPHYLAXIS CHART ABSTRACTION FORM

DRAFT

FACE SHEET

AUTOMATED DATA:

VSD ID: ____________________

HMO ID: ___________________

Reference diagnosis date: ____/____/____

Reference diagnosis code: ________________________________

TO BE COMPLETED BY ABSTRACTOR:

Charts reviewed:

[ ] All charts [ ] Partially (explain) _______________________ [ ] None (explain) _________________________

Abstractor ID: __________________

DIAGNOSIS VALIDATION & PATIENT DISPOSITION

1. Anaphylaxis diagnosis in chart on or near reference date?

2. Date of anaphylaxis diagnosis: ____/____/____ (as noted in the medical record and if different than reference date)

3. Encounter type (as noted in the chart):

4. Was this episode of anaphylaxis felt by the provider to be result of any of the following exposures:

a. Food

b. Drugs (other than vaccines) [ ] Yes stop abstraction [ ] No/Unknown

c. Exercise [ ] Yes stop abstraction [ ] No/Unknown

d. Latex (other than in vaccine stopper) [ ] Yes stop abstraction [ ] No/Unknown

e. Insect sting (bee, fire ants, etc.)

[ ] Yes stop abstraction [ ] No/Unknown

f. Other (not vaccine-related) [ ] Yes stop abstraction [ ] No/Unknown

g. Unknown (Provider notes in chart that cause is unknown) [ ] Yes go to question 5 [ ] No/Unknown

h. Vaccine(s) [ ] Yes List vaccines received within 3 days of date of anaphylaxis diagnosis:

1)_______________ Date of vaccination: ____/____/_____

2)_______________ Date of vaccination: ____/____/_____

3)_______________ Date of vaccination: ____/____/_____

[ ] No/Unknown

5. What was the time interval between the exposure and the onset of symptoms?

SIGNS AND SYMPTOMS

Please record signs and symptoms noted by the clinician during the reference visit

6. Dermatologic and Mucocutaneous

7. Respiratory

8. Cardiovascular

10. Neurologic (please note any neurologic symptoms, but do not use this when deciding to accept or reject a case)

TREATMENTS

12. Were any of the following treatments used during the anaphylaxis episode? (check all that apply)

[ ] Epinephrine (adrenalin) [ ] Parenterally administered antihistamines (Diphenhydramine (benadryl), Cimetidine, ranitidine)

HISTORY

13. Did the patient have a history of any of the following conditions or medications?

[ ] Atopic dermatitis [ ] Contact dermatitis

[ ] Albuterol or other inhaler (e.g. cromolyn or steroid-containing inhaler)

COMMENTS

TO BE COMPLETED BY ADJUDICATOR:

Final Disposition:

If accepted, does this case meet the Brighton Collaboration Definition for anaphylaxis?

[ ] Yes [ ] Level 1 of diagnostic certainty [ ] No [ ] Level 2 of diagnostic certainty [ ] Level 3 of diagnostic certainty

12.1 Brighton Collaboration Case definition of anaphylaxis14

For all levels of diagnostic certainty Anaphylaxis is a clinical syndrome characterized by

· sudden onset AND

· rapid progression of signs and symptoms, AND

· involving multiple (> 2) organ systems, as follows

Level 1 of diagnostic certainty

· > 1 major dermatological AND

· > 1 major cardiovascular AND/OR > 1 major respiratory criterion

Level 2 of diagnostic certainty

· > 1 major cardiovascular AND > 1 major respiratory criterion

OR

· > 1 major cardiovascular OR respiratory criterion AND

· > 1 minor criterion involving > 1 different system (other than cardiovascular or respiratory systems) OR

· (> 1 major dermatologic) AND (> 1 minor cardiovascular AND/OR minor respiratory criterion)

Level 3 of diagnostic certainty

· > 1 minor cardiovascular OR respiratory criterion AND

· > 1 minor criterion from each of > 2 different systems /categories

12.2 Major and minor criteria used in the case definition of anaphylaxis: Brighton Collaboration Criteria

Major criteria

Minor criteria

· angioedema*, localized or generalized

· generalized pruritus with skin rash

· generalized pruritus without skin rash

· generalized prickle sensation

· localized injection site urticaria

· red and itchy eyes

· clinical diagnosis of uncompensated shock, indicated by the combination of at least 3 of the following:

· tachycardia

· capillary refill time > 3s

· reduced central pulse volume

· decreased level of consciousness or loss of consciousness

· reduced peripheral circulation as indicated by the combination of at least 2 of

· tachycardia and

· a capillary refill time > 3s without hypotension

· a decreased level of consciousness

· stridor

· upper airway swelling (lip, tongue, throat, uvula or larynx)

· respiratory distress-2 or more of the following:

· tachypnea

· increased use of accessory muscles (sternocleidomastoid, intercostals, etc.)

· recession

· cyanosis

· grunting

· persistent dry cough

· hoarse voice

· difficulty breathing without wheeze or stridor

· sensation of throat closure

· sneezing, rhinorrhea

Gastrointestinal

· diarrhea

· abdominal pain

· nausea

· vomiting

Laboratory

· mast cell tryptase elevation >upper normal limit

*Not hereditary angioedema

13. Algorithm for assessing anaphylaxis: from Bohlke et al.13 image1.jpeg