example of bias matched case-control study lakkana thaikruea md., cert of fetp, m.s., phd....
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Example of Bias Matched Case-Control Study
Lakkana Thaikruea
MD., Cert of FETP, M.S., PhD.Department of Community Medicine, Faculty of Medicine, CMU
Risk Factors for Hepatitis C Virus infection Risk Factors for Hepatitis C Virus infection among Blood Donors in Northern Thailandamong Blood Donors in Northern Thailand
Lakkana Thaikruea 1,
Satawat Thongsawat 1,
Niwat Maneekarn 1,
David L. Thomas 2,
Dale Netski 2,
Kenrad E. Nelson 2, 1 Departments of Community Medicine, Medicine, and Microbiology, Chiang Mai University, Chiang Mai, Thailand
2 Departments of Epidemiology & Medicine, Johns Hopkins University, Baltimore, USA
Rationale No effective program in Thailand to prevent HCV
infection Lack of information of majors route of
transmission Distribution of HCV genotypes are not well
understood Researchers from JHU and Chiang Mai
University have conducted study about epidemiology of HCV in northern Thailand
Blood donor is one of the study population besides drug users, patients, and commercial sex workers
This present study focuses on blood donor
Specific aimsSpecific aims
Blood donors in northern Thailand
1. To investigate the potential risk factors
for HCV infection
2. To determine HCV genotype distribution
3. To investigate relationship between HCV
genotype distribution and the routes of
transmission
Features of hepatitis C virus infection
Resolve 15--
Stable 68--
Stable 13---
M ortality 4
Cirrhosis 17
Chronic 85
100--
15% 85%
80% 20%
75% 25%
Background: Route of transmission USA:
IDU1, sex with an IDU,
blood transfusion among non-IDU REDS2:**
male, black, 30 to 49 years,
< high school diploma,
first /only time blood donor,
blood transfusion history1 Injection drug users ; 2 Retrovirus Epidemiology Donor Study
Specific aim 1Specific aim 1
To investigate the potential risk factors for HCV infection among blood donors in
northern Thailand
Study settingStudy setting
Faculty of Medicine, CMU The Blood Bank
- The Maharaj Nakorn Chiang Mai hospital- 1,800-bed capacity and the main referral center
Blood donors- January 2001 - June 2002- ≥ 18 years old at the time of donation/ recruitment- Reside in the north- Donation sites: walk-in and mobile unit
Methods (cont.)
Study design: Specific aim 1Study design: Specific aim 1
Single masked matched case- control Matched variables:
age, gender, donation date, donation sites
Mask: interviewers and physicians did not know HCV status of the participants
Methods (cont.)
Data collection
Invitation letters: 2nd letter in 2 weeks apart Non-participants: sent their participation forms
indicating their unwillingness Enrolment: explain, consent form Trained health personnel of the same gender: face-to-
face interview Physical examination Counseling Laboratory tests: 30 ml blood
– HCV antibodies; EIA-3, RIBA-3– HCV RNA: RT-PCR– HCV genotypes: direct sequencing– Serum ALT
Eligible Case: blood bank EIA-3 positive
Data collection (cont)
PCR positive, or PCR negative with RIBA-3 positive, or PCR negative with both
– positive high cut-off repeat EIA-3 (Abbot)– positive high cut-off repeat EIA-3 (Ortho)
Eligible cases were defined as “confirmed cases ”
If they were HCV EIA-3 positive in blood bank screening and had any of the following:
Data collection (cont.)
Randomly selection: – 1 – 4 eligible controls per case
Matched variables: – ± 15 days of case’s donation date – Age ± 5 years old– Same gender– Same donation sites
Enrolment: same Control:
– Negative to both screening EIA-3 and repeat EIA-3
Eligible Control: blood bank EIA-3 negative
Data collection (cont.)
Spouses of cases and matched controls– Regular sexual relations with the donor
for ≥ 3 months – ≥ 18 years old at the time of recruitment
Enrolment: same HCV infection:
– EIA-3 positive and– Either PCR or RIBA-3 positive
SPOUSES
Flow of matched case-control study Flow of matched case-control study
102 low cut-off EIA-3 positive28 not eligible EIA-3 positive
665 participants
411 matched controls
329 matched controls
254 eligible cases
175 confirmed cases
166 confirmed cases
38,340 donors
372 EIA-3 pos Eligible cases
372 eligible cases 1234 eligible matched controls 618 non-responders
85 returned letters 903 responders
238 non-participants
67 false positive cases12 RIBA-3 indeterminate
82 matched controls
9 cases without control
Participation
Compared between participants and non-participants
Cases: 254 participants (91.4%) versus 24 non-participants
– No statistically significant different Controls:411 participants (65.8%) versus
214 non-participants
– Participants: age in years 33.2 ( VS 31.0)* – Participants: ever donated 81.6 % (VS 61.3 %)*
* P value < 0.05
Data analysis: Specific aim 1 Univariate analysis
– Matched odds ratio (OR) with 95% confidence interval (95% CI) Multivariate analysis
– Conditional logistic regression – Step-wise selection:
• alpha levels of 0.05 for entry and 0.0501 for remove • to guide the selection of variables
– Either independent variables that were likely confounders or had biological importance were forced in to the preliminary model regardless of their statistical significance
Phylogenic analysis 1
– Tree was constructed from nucleic acid sequence alignments using Neighbor joining method
– Sequence alignments were randomly permuted 1,000 times• CONSENSE provided bootstrap values
– Reference sequences: GenBank 1 programs: Gofasta1.1, BioEdit 5.9, Tree View 1.6 , PHYLIP 3.572c package ( SEQBOOT, DNADIST,
NEIGHBOR, CONSENSE)
Limitations: Specific aim 1
Limitations:
- causal relationship; temporal ambiguity
- spouses; might not represent
Strengths: Specific aim 1- appropriate study design;
• sample size• matched case-control• confounding
- minimized selection bias;• asymptomatic nature• lacked HCV knowledge • available of HCV test only in some secondary or tertiary cares• self-deferral system
- minimized information bias;• masked• face-to-face interview• physical examination
- minimized misclassification of HCV status;• confirmatory tests
Publications
The risk factors for HCV infection among blood donors in northern Thailand: Matched case-control study.
Presenter: Lakkana Thaikruea (The XV International AIDS Conference. July 10-16, 2004.
Bangkok, Thailand)
Risk Factors for Hepatitis C Virus Infection Among Blood Donors in Northern Thailand
Lakkana Thaikruea1,6, Satawat Thongsawat3,6, Niwat Maneekarn4,6, Dale Netski 5, David L. Thomas ,5 Kenrad E. Nelson2 (Transfusion, 2004 - in process)
Other Related Publications
Epidemiology of hepatitis C virus infection among blood donors in northern Thailand
Presenter: Lakkana Thaikruea (International Centers for Tropical Disease Research
Network, 12th Annal Meeting, May 13-15, 2003, NIH, Bethesda, MD, USA)
Relationship between HIV and Hepatitis C Viral Genotypes and Routes of Transmission among Blood Donors in Northern Thailand.
Presenter: Lakkana Thaikruea) (11th CROI retrovirus and Opportunistic Infection
Conference, Feb 7-11, 2004, San Francisco, CA , USA)