Amra Uzicanin, MDAmra Uzicanin, MDLaura Zimmerman, MPHLaura Zimmerman, MPH

Global Immunization Division, CDC AtlantaGlobal Immunization Division, CDC Atlanta

Field Effectiveness of Measles-Containing Vaccines- Literature Review -

Meeting of the SAGE Working Group for MeaslesGeneva, Switzerland, January 29-30, 2009

Overview

• Study Objective• Methods

– Literature search– Data abstraction– Data analysis

• Results (prelim.)• Limitations• Conclusions (prelim.)

Study Objective• To provide additional information for the

discussion about the need for a routinely scheduled second dose of measles-containing vaccine (MCV2) by:

– Conducting a review published literature on effectiveness of live attenuated measles vaccines in field conditions (VE)

– Summarizing the available VE data by age of administration of the first dose of measles-containing vaccine (MCV1)

Methods (1)Literature Search

• Used Medline and PubMed to identify published English-language articles with estimates of MCV field effectiveness – Utilized the following search strategies:

• Searched titles for different combinations of following terms: measles, mumps rubella vaccine; measles vaccine; outbreak; effectiveness; efficacy; vaccine failure;

• Searched for key words: (measles-mumps-rubella vaccine ormeasles vaccine) + (efficacy or effectiveness)

• Reviewed article references and Vaccines (5th ed.) chapter references to identify any additional papers

• Included only the studies that evaluated the success of measles vaccinations performed under field conditions by estimating the vaccine effectiveness (VE) using one or more field methods described by Orenstein et al. (Bull WHO, 1985)

• Abstracted data from each article*– Key variables included (but not limited to):

• Study design• Country / WHO region• Ages under assessment and their birth cohorts• Scheduled age at 1st dose• Vaccine type / strain where available• Vaccine effectiveness point estimate (VE)• VE 95% confidence intervals where available

Methods (2)Data Abstraction

*An article may include several estimates (ie, different ages of vaccine receipt or types of studies [eg, cohort, case control, screening])

• Excluded speculated VE estimates which were presented in some studies as an attempt to address possible study biases (egmisclassifications based on vaccination/disease/susceptibility status, etc)

• Included VE estimated for the overall study sample (where provided), and stratified by age of receipt of 1st dose of MCV (9-11 months and 12+ months)

• Calculated summary statistics for the published VE point estimates globally and by WHO region

Methods (3)Data Analysis

Preliminary Results

MCV1: Overview of Included Papers

Earliest Most Recent

Overall: 69 1969 2006

By Study Design:Case control 10 1984 2006Cohort 56 1969 2006Screening 3 1990 2001

By WHO Region:AFR 17 1981 2000AMR 17 1969 2003EMR 2 1990 1995EUR 14 1988 2006SEAR 5 1989 2001WPR 14 1978 2004

By age of 1st dose*:9-11 m 39 1969 200612+ m 38 1972 2006

MCV1 VE studies included in the review

* A number of studies evaluated VE in more than one age group.

No. studiesRange of years when

studies conducted

MCV1: Vaccine Type(N=69 Studies)

• Unspecified – n= 50 (72%)• Live attenuated – n= 4 (6%)

– Unspecified – n=3 – Edmonston – n=1

• Live further attenuated – n=15 (22%)– Unspecified – n=2– Moraten – n=1– Schwarz – n=10– AIK-C – n=1– L-16– n=1

MCV1 by age of administration

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

1.10

MCV1 (9-11 m) MCV1 (12+ m) MCV1 (any age)

VE p

oint

est

imat

es

q1 min median max q3

MCV1 administered at 9-11m, by WHO Region

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

1.10

AFR AMR EMR EUR SEAR WPR

VE p

oint

est

imat

es

q1 min median max q3

MCV1 administered at 12+m, by WHO Region

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

1.10

AMR EMR EUR SEAR WPR

VE p

oint

est

imat

es

q1 min median max q3

MCV2: Overview of included papersEarliest Most Recent

Overall, 2 doses vs 0 doses: 8 1994 2006

By Study Design:Cohort 7 1994 2006

Case control 1 2006

By WHO Region:AMR 2 1995 2003EUR 4 1996 2006WPR 2 1994 2003

By Age of 1st dose*:9-11 m 3 1996 2006>=12 m 8 1994 2006

Overall, 2 doses vs 1 dose: 4 1988 1998(all cohort studies)

By WHO Region:AMR 3 1994 1998EUR 1 1988

By Age of 1st dose9-11 m 1 1988>=12 m 3 1994 1998

Summary Results

*A number of studies presented more than one VE point estimate.

No. studiesRange of years when

studies conducted

MCV2: Vaccine Type(N=12 Studies)

• Unspecified – n= 9 (75%)• Live further attenuated – n=3 (25%)

– Unspecified – n=1– Schwarz – n=1– L-16– n=1

2 doses vs 0(by age of MCV1 administration)

0.5

0.6

0.7

0.8

0.9

1

1.1

2 doses(MCV1 at 9-11 m) vs 0 2 doses(MCV1 at 12+ m) vs 0 2 doses(MCV1 at any age) vs 0

VE p

oint

est

imat

es

q1 min median max q3

2 doses vs 1(by age of MCV1 administration)

0.50

0.60

0.70

0.80

0.90

1.00

1.10

2 doses vs MCV1 (9-11m) 2 doses vs MCV1 (12+ m) 2 doses vs MCV1 (any age)

VE p

oint

est

imat

es

q1 min median max q3

Are two doses “better” than one?

MCV1 vs. MCV1+2 (MCV1 given at 9-11m)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

1.10

MCV1 (9-11 m) 2 doses (MCV1at 9-11 m) vs 0 2 doses vs MCV1 (9-11m)

VE p

oint

est

imat

es

q1 min median max q3

MCV1 vs. MCV1+2 (MCV1 given at 12+ m)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

1.10

MCV1 (12+ m) 2 doses (MCV1 at 12+ m) vs 0 2 doses vs MCV1 (12+ m)

VE p

oint

est

imat

es

q1 min median max q3

Limitations• Our search strategy may have missed some

publications relevant for this topic• Characteristics of the included papers

– Limitations inherent to the study design – Completeness and quality of the data at hand– Uneven distribution of studies between and within

geographic regions • Few published MCV1+2 VE estimates• Publication bias: unpublished VE studies with

possibly different results than published ones?• Data analysis still ongoing

Preliminary Conclusions• When MCV1 is administered at 9-11 months:

– Overall, MCV1 VE appears lower than the usually assumed value of 85%

– Summary estimates vary between the regions• VE IQR

Backup Slides

Two MCV doses vs. 0

Earliest Most Recent Min Max

Overall: 8 1994 2006 99% 94% 10% 67%** 99%

By Study Design:Cohort 7 1994 2006 99% 94% 10% 67%** 99%

Case control 1 2006

By WHO Region:AMR 2 1995 2003 83% 83% 23% 67%** 99%EUR 4 1996 2006 99% 98% 3% 92% 99%WPR 2 1994 2003 92% 92% 5% 88% 95%

By Age of 1st dose*:9-11 m 3 1996 2006 96% 97% 2% 95% 99%>=12 m 8 1994 2006 99% 93% 11% 67%** 99%

Summary Results

VE Point EstimateNo. studies

VE Point estimate = 92% (95% CI: 79% - 97%)

RangeMedian Mean SD

Range of years when studies conducted

Two MCV doses vs a single dose

Earliest Most Recent Min Max

Overall: 4 1988 1998 92% 93% 5% 89%** 100%(all cohort studies)

By WHO Region:AMR 3 1994 1998 94% 94% 6% 89%** 100%EUR 1 1988

By Age of 1st dose9-11 m 1 1988>=12 m 3 1994 1998 94% 94% 6% 89%** 100%

Median Mean SD Range

VE Point estimate = 90% (95% CI: 15% - 99%)

VE Point estimate = 90% (95% CI: 15% - 99%)

Summary Results

No. studies

Range of years when studies conducted

VE Point Estimate

Field Effectiveness of Measles-Containing Vaccines�- Literature Review -��Meeting of the SAGE Working Group for Measles�GenevaOverviewStudy ObjectiveMethods (1)�Literature SearchMethods (2)�Data AbstractionMethods (3)�Data AnalysisPreliminary ResultsMCV1: Overview of Included PapersMCV1: Vaccine Type�(N=69 Studies)MCV1 by age of administrationMCV1 administered at 9-11m, by WHO RegionMCV1 administered at 12+m, by WHO RegionMCV2: Overview of included papersMCV2: Vaccine Type�(N=12 Studies)2 doses vs 0�(by age of MCV1 administration)2 doses vs 1�(by age of MCV1 administration)Are two doses “better” than one?MCV1 vs. MCV1+2 (MCV1 given at 9-11m)MCV1 vs. MCV1+2 (MCV1 given at 12+ m)LimitationsPreliminary ConclusionsBackup Slides Two MCV doses vs. 0Two MCV doses vs a single dose