preferences for seasonal influenza vaccine for working adultsin ho chi minhcity a discrete choice experiment

UNIVERSITY OF ECONOMICS HO CHI MINH CITY MINH HAI, PHAN PREFERENCES FOR SEASONAL INFLUENZA VACCINE FOR WORKING ADULTS IN HO CHI MINH CITY: A DISCRETE CHOICE EXPERIMENT THESIS FOR MAST

UNIVERSITY OF ECONOMICS HO CHI MINH CITY

MINH HAI, PHAN

PREFERENCES FOR SEASONAL INFLUENZA VACCINE FOR WORKING ADULTS IN HO CHI MINH CITY: A DISCRETE CHOICE

EXPERIMENT

THESIS FOR MASTER OF HEALTH ECONOMIC MANAGEMENT

Ho Chi Minh, City – 2015

UNIVERSITY OF ECONOMICS HO CHI MINH CITY

MINH HAI, PHAN

PREFERENCES FOR SEASONAL INFLUENZA VACCINE FOR WORKING ADULT IN HO CHI MINH CITY: A DISCRETE CHOICE

EXPERIMENT

Faculty: Development Economic Code: 60310105

THESIS FOR MASTER OF HEALTH ECONOMIC MANAGEMENT

INSTRUCTOR: DR DANG THUY, TRUONG

Ho Chi Minh, City – 2015

Introduction: Seasonal influenza is viral infection which affects 5%–10% in adults and 20%–30% in children, and the influenza vaccine, also known as flu shot, is an annual vaccination using a vaccine that is specific for a given year There is increasing interest in benefit of vaccination coverage in health working adults which reduced work loss From 2005, the vaccine manufacturing capacity are increasing globally and especially

in Viet Nam, that would support in price and number of doses in broadening the vaccination We conduct the study to assess the influencing factors for vaccination in working adults and how to increase the vaccination in population via the willingness to pay model

Method: We conducted a discrete choice experiment, a quantitative approach which often used in health economic studies In which, the questionnaire with socio-economic and discrete choice experiment questions was collected for 172 respondents The conditional logit model was used to estimate the relative importance of influenza vaccine attributes: effectiveness (50%, 70%, 90%); adverse event (0%, 5%,10%), time of vaccination process (45 minutes, 60 minutes, 90 minutes); place of vaccination (working place, healthcare center); cost (150,000 VND 200,000 VND 250,000 VND and 300,000 VND) Based on the utility functions, the willingness to pay and potential vaccination coverage was estimated for different vaccine scenarios and price support strategy

Result: The results indicated the effectiveness and adverse event are two valuable influence (p value<0.1), and the cost dose not impact significantly to the decision of vaccination Meanwhile, the coefficient of place of vaccination is too high which is suspected as implausible value

Conclusion: Respondent would choose the high effectiveness and low adverse event for vaccination, by contrast, it will reduce the preference if high cost, long time for vaccination, and working place The availability of more than 1 vaccine can increase the number of vaccination cases, then the well-fare were also increased It could be explained

the statistical number could help us to predict the trend of vaccination, but the education to community is very important

Keywords: Working adults, influenza vaccination, and discrete choice experiment, utility, conditional logit model

I would like to deeply express my gratitude and appreciation to Dr Truong Dang Thuy, who provided the intensive, supportive, valuable and vital supervision for thesis completion I had a great opportunity to access the econometric method and how to apply

in Viet Nam which has very a few application in health sectors I was inspired by his knowledge, enthusiasm and professionalism

Throughout my thesis process, he was always patient, supportive in the right directions, encouraged me to pursue my own research ideas and provided a great amount

of valuable suggestions and guidance I appreciate all his contributions of time, advice to make me successfully complete the thesis

I would like to express my appreciation and respect for teachers of master of health economic management program, who have delivered the useful and practical knowledge

in health economic, which I had perceived at the first time

I would also like to thank all the faculty, staff and students for their friendships and collaboration during last 2 years

I would like to be grateful to my colleges, friend and especial my bother in supporting me for business, life and activities of data collection

Thanks for my family always as my support overcomes all the difficulties and pursue the real goal in my life

With all appreciation, HCM, Aug 2015

ABSTRACT 2

ACKNOWLEDGEMENT 4

TABLE OF CONTENT 5

ABBREVIATION 9

CHAPTER 1: INTRODUCTION AND RESEARCH ISSUE 1

1 Introduction 1

1.1 Introduction of Influenza 2

1.2 Burden of influenza 3

1.3 Influenza vaccination 4

2 Research objectives 4

2.1 Problem issue 4

2.2 Research objective 5

2.3 Research methodology and organization of thesis 6

CHAPTER 2: LITTERATURE REVIEW 7

1 Random utility Theory (RUT) 7

2 Lancaster's New Approach to Consumer 8

3 Data collection method 9

3.1 Contingent valuation method 9

3.2 Discrete choice experiment 10

4 Applications of discrete choice experiments in health care 11

Relevant attributes 12

Levels of attribute 13

Discrete choice experiments design 13

Model estimation 15

Validity issues 16

5 Discrete choice experiment application in healthcare, Viet Nam 17

6 Discrete choice experiment application in seasonal influenza vaccine 18

CHAPTER 3: RESEARCH METHODOLOGY 21

2 Discrete choice experiment construction 22

2.1 Identification of relevant attributes 22

2.2 Selection of attributes 26

2.3 Definition of levels 28

3 Discrete choice experiment design 33

3.1 Discrete choice experiment design 33

3.2 Design evaluation and modification 34

3.3 Questionnaire design 36

3.4 Data collection 36

CHAPTER 4: RESULT 38

1 Demographic and history 38

1.1 Socio-economic 38

1.2 Influenza and vaccination 40

2 Model estimation 40

2.1 Conditional logit model result 40

2.2 Model interpretation: 43

2.3 Willingness to pay for vaccine 44

2.4 Predicting influenza vaccination uptake rate for existing vaccine 45

2.5 Assess the feasibility of new vaccine 47

2.6 Compensating Variation (CV) 48

2.7 Vaccination up-take 50

2.8 Interaction between “non-vaccination” and socio-economic 51

CHAPTER 5: DISCUSSION AND CONCLUSION 53

Reference

APPENDIX 1 Short survey for importance of attributes relating to influenza vaccination

APPENDIX 2 (Questionnarie#1: Survey for the factors of influenza vaccination)

Table 1: Example of choice set of discrete choice experiment design 11

Table 2: Attributes and levels of influenza vaccine in Japan 18

Table 3: Willingness to pay for influenza vaccine in Japan 20

Table 4: Primary list of characteristics and attributes influencing choice of influenza vaccination 23

Table 5: Secondary list of attributes influencing influenza vaccination up-take 25

Table 6: Result of survey for influencing attributes 27

Table 7: Level of vaccinating time 32

Table 8: Levels of unacceptable cost 32

Table 9: T-test of level of unacceptable cost 33

Table 10: Attributes and levels 33

Table 11: Orthogonality design 34

Table 12: 16 choice sets of discrete choice experiment design 37

Table 13: Socio-economic summary 39

Table 14: Influenza infection and vaccination history 40

Table 15: Marginal willingness to pay 44

Table 16: Willingness to pay for vaccine 45

Table 17: An example of predicting influenza vaccination uptake for existing vaccine 46

Table 18: New vaccine versus existing vaccine and non-vaccination 47

Table 19: CV for price support program versus new vaccine introduction 49

Table 20: The probability of vaccination for the 16 hypothetical vaccines: 51

Table 21: interaction with “non-vaccination” 52

Figure 1: The percentage of specimens (ILI or SARI) positive for influenza (average:

20.37% for Viet Nam (from week 1-2014 to week 18 – 2015)) 3

Figure 2: Average of health-related DCE studies/year 12

Figure 4: Number of attributes 26

Figure 5: Example of effectiveness explanation 29

ABBREVIATION

AE: Adverse Event

CV: Compensating Variation

CVM: Contingent Valuation Method

DCE: Discrete Choice Experiments

LIV: Live attenuated influenza vaccine

MNL: The MultiNomial Logit

MWTP: Marginal willingness to pay

RP: Revealed Preference

SP: Stated Preference

TIV: Trivalent inactivated influenza vaccine

WTP: Willingness To Pay

CHAPTER 1: INTRODUCTION AND RESEARCH ISSUE

1 Introduction

The finite health care resources (including capital, medical treatment capacity) and rising costs requests the government to determine which health service/treatment to be provided and the appropriate level at which to provide them By providing information of benefit valuation to assess alternative health care solution to matters, the health economics has been developing and playing the key role in health policy The application of health economics is to obtain the maximum value for money with evaluation techniques including cost minimization analysis, cost effectiveness analysis, cost utility analysis and cost benefit analysis By starting to identify the important health issue, the health economists will explore the appropriate method to assess the alternatives

Seasonal influenza is the virus infection, which caused the respiratory disease, with most mild cases but widely impacted It is the major economic burden and potential pandemic The World Health Organization cites studies from developed countries that suggest the total annual cost of influenza is between U$1 million to U$6 million per 100,000 population

Influenza infection can result in increased healthcare costs (direct cost) and workplace absences and reduced productivity (indirect cost) Studies shows the indirect cost occupies over 50% of total cost of influenza cases With 48.4% population in age group of 25-54 years, the indirect cost of influenza could contribute the high proportion of health cost in Viet Nam

Vaccination is the most effective measure at preventing influenza and its severe outcomes But the vaccination rate is low for Southeast Asia including Viet Nam, with less than 1% vaccination in total population The vaccine manufacturing program is expected

to supply 500 millions of influenza vaccine in 2016, which is enough to cover the vaccination for all Southeast Asia countries

This thesis is to answer how to increase the vaccination rate in working adults to provide the policy-makers information to assess the alternatives

1.1 Introduction of Influenza

Seasonal influenza infection

Influenza is a viral infection (including influenza A and influenza B strains) that affects mainly the nose, throat, bronchi and, occasionally, lungs Infection usually lasts for about a week, and is characterized by sudden onset of high fever, aching muscles, headache and severe malaise, non-productive cough, sore throat and rhinitis

The virus is transmitted easily from person to person via droplets and small particles produced when infected people cough or sneeze Influenza tends to spread rapidly in seasonal epidemics

Most infected people recover within one to two weeks without requiring medical treatment But, the high-risk persons (age below 2 or above 65 years old, pregnant women and people of any age with certain medical conditions) are vulnerable to the complications

of influenza that cause the hospitalizations, deaths and high healthcare costs Meanwhile,

in health working adult group, the major impact of influenza is related to work absenteeism, impaired working performance and daily activities

Influenza prevalence (WHO, 2013)

The Global Influenza Surveillance and Response System (GISRS) consists of over

140 National Influenza Centers around the world that collect and test clinical specimens, submitting a sample of these to WHO Collaborating Centers and Essential Regulatory Laboratories The Influenza-Like Illness or Severe Acute Respiratory Infection cases could

be caused by a variety of microbial agents other than influenza viruses

ILI case definition: an acute respiratory infection with measured fever of >=38oC, and cough, with onset within the last 10 days

SARI case definition: an acute respiratory infection with history of fever >= 38oC, and cough, with onset within the last 10 days, and requires hospitalization

As the primary goal of influenza surveillance is to recognize trends, describe patterns of risk, and estimate impact, it is not necessary to identify every cases So the case definition of ILI and SARI was used for doing the influenza surveillance and integrating with virological laboratory test (the most common method is: Real-time reverse transcription polymerase chain reaction) for data

The patients who attended outpatient department or admitted a sentinel hospital, will be collected for specimen if meeting the clinical case definition for SAR or ILI, and the onset of symptoms falls within 10 days of sample collection

The data of Viet Nam from 1st week of 2014 to 18th week of 2015 was extracted from GISRS to show the average of 20.37% positive influenza among ILI/ SARI

Figure 1: The percentage of specimens (ILI or SARI) positive for influenza (average:

20.37% for Viet Nam (from week 1-2014 to week 18 – 2015))

1.2 Burden of influenza

According to WHO, influenza occurs globally with an annual attack rate estimated

at 5%–10% in adults and 20%–30% in children result, with about 3 to 5 million cases of severe illness, and about 250 000 to 500 000 deaths In tropic coutries, influenza-related

deaths are estimated to range from 4 to 20 deaths per 100,000 persons (Sophia Ng and Aubree Gordon, 2015 Apr) A national surveillance from 2006-2010 in 15 hospital sentinels of Viet Nam, the 19% of hospitalization with ILI is positive with influenza viruses In another literature review for South-East Aisa from 1980 to 2006, 11-26 % of outpatient febrile illness and 6-14% of hospitalized pneumonia cases had laboratory confirmed influenza infection (James M Simmerman and Timothy M Uyeki, 2008)

A systemtic review study (includes 140 articles, before 2010) estimated for the per capita cost (indirect and direct cost) of case of influenza illness ranged from 27-52 USD (or 0.04-0.13%GDP) in European countries, 45-63 USD (or 0.14%GDP) in US, 3 USD (or 0.01%GDP) in Hong Kong, and 01 USD (or 0.02%GDP) in Thailand The percentage of total cost for productivity losses (indirect cost) was more than 80% in European countries (except Spain), 38% in US, 12.5% in Hong Kong and 55.3% in Thailand

1.3 Influenza vaccination

The influenza vaccine, also known as flu shot, is an annual vaccination using a vaccine that is specific for a given year to protect against the highly variable influenza virus (Couch, 2008)

Generally, the influenza vaccines included the common trivalent strains (mixture of Influenza A (H1N1; H3N2) and influenza B strains) were produced into two kinds of form: the trivalent inactivated influenza vaccine (TIV) and the live attenuated influenza vaccine (LAIV) In Viet Nam, the TIV is the most popular and being circulated in market, so the data of TIV was used for model

The antigenic properties of influenza viruses are highly variable, so the annual vaccination is required to have the effective immunogenicity

2 Research objectives

2.1 Problem issue

The cost-effectiveness of influenza vaccination in risk group was widely accepted and high recommended by WHO However, there is increasing interest in benefit of

vaccination coverage in health working adults which reduced work loss In cost-saving annalysis, when the indirect costs included, the vaccination in adults under age 65 is still highly cost effective With over fifty millions of employed persons, the benefit of vaccination in working adults should be considered for Viet Nam

Moreover, the anaylysis of genome sequences by Nelson et al found evidence compatible with either northern-to-southern hemisphere migration or migration from tropical regions, including Southeast Asia (Russell CA et al., 2008) For this point of view,

a relatively high vaccination coverage which creates the strong community immunity to be achieved, that would prevent the transmission and mutation (Anon., 2015) The study in USA, France and Australia suggests that interrupting transmission of seasonal influenza would require a relatively high vaccination coverage (>60%) in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and warning population immunity (G CHOWELL1, 2008)

The vaccine sale during 2010-1011 is less than 1000 per 100,000 population in South-East countries, it implies that vaccination is very low (Gupta V et al., 2012) It could

be caused by vaccine capacity or the policy of influenza vaccine programme in that countries

From 2005, the vaccine manufacturing capacity are increasing globally and especially in Viet Nam, that would support in price and number of doses in broadening the vaccination (Anon., 2013) Once the vaccine capacity addressed, the question on how to increase the vaccination in population will be an issue to be addressed, especially for majority of working adults in Viet Nam

- The vaccination strategy for achieving the community immunity

2.3 Research methodology and organization of thesis

This thesis is based on the random utility theory, and the stated preference choice experiment is used to collect the choice from respondents for influenza vaccination Discrete choice experiment was chosen as the approach of stated preference which is advantage in evaluating the different features of vaccination

Chapter 2 provide the overview of customer theory, random utility maximization (RUM) and the literature review

Chapter 3 describes choice discrete choice experiment and the design of survey

Chapter 4 presents the empirical estimation results of vaccination choice

Chapter 5 provides conclusions and discussions on the limitation of study as well as the suggestions for future research

CHAPTER 2: LITTERATURE REVIEW

1 Random utility Theory (RUT)

Random utility models, a subset of the class of probabilistic choice models, were firstly developed by psychologists in the attempt to characterize observed inconsistencies

in pattern of individual behavior In 1927, Thurstone identified the comparison process (known as Thursone’s Law) with below assumptions:

 Assumption one is that choice is a discrete event Customer cannot leave market with 0.3432 cans of Coke and 0.6568 cans of Pepsi, but need to leave with 1 cans of their chosen brand, and 0 cans of their not chosen brand

 Assumption two is that the attraction or utility towards a brand varies across individuals

With is an alternative-specific constant captures the mean effect of the unobserved factors in the error term for each of the alternative

The individual choice probability is given by: (Ben-Akiva, M and Lerman, S., 1985)

Most commonly, welfare analysis refers to the estimation of WTP for policy changes And if there is no income effect (i.e no change in purchasing power), the compensated demand curve can be considered to be equivalent to customer surplus Customer surplus can be defined as the maximum utility, in monetary terms, an individual receives by choosing the alternative in a choice situation A general formula to estimate mean aggregate Willingness To Pay (WTP) (compensating variation or CV) for a determined change is (Small, K.A and Rosen, H.S., 1981) (Williams, H.W.C.L, 1977):

2 Lancaster's New Approach to Consumer

The traditional approach sates that goods are the direct objects of utility and goods are consumed not because they have intrinsic value but because they are goods The new approach supposes that it is the properties or characteristics of the goods from which utility is derived

It assumes that consumption, singly or in combination, are inputs and the output that we get is a combination of characteristic A product does not have only one

characteristic but may have numerous characteristics which may other products may share A product does not have to be a close substitute to share the same properties but may vary to the extent of a diamond to bread

The essence of the new approach can be summarized in the following three points:

1 The goods, per se, do not give utility to the consumer It possesses

characteristics which gives rise to utility

2 In general, a good may possess more than one characteristic, and many

characteristics will be shared my more than one good

3 Goods in combination may possess characteristics different from those

pertaining to the goods separately

3 Data collection method

There are two fundamental pathways in data collection for monetary benefit

valuation including “stated preference” (SP), and “revealed preference” (RP) SP relies on what customers say they will do, and RP relies on what they actually do RP is market

data, used for product/service which had been launched

The monetary terms in health care is a remarkable issue to policy decision-maker including government and pharmaceutical companies, and the health services/products are usually not traded or characters can be changed (such as efficacy, safety, consequence, or administration) There are a number of compelling reasons why health economists should

be interested in SP data The most importance in the health sector is that it may not be possible to infer consumer preferences or values from RP The two best-known SP

approaches for providing estimates of monetary valuation are the contingent valuation method (CVM) and discrete choice experiments (DCE)

The choice of SP method depends, in part, on how much detail is required on the

characteristics of the health care intervention being valued A CVM is appropriate for answering questions only about the good or service as a whole (e.g what is the monetary value placed on a screening test) In other contexts, what matters is the importance of different characteristics of the programme being valued In these cases, DCEs are more useful To the extent that DCEs also allow estimating total values, they provide more information than a single (CVM) experiment (Ryan M et al., 2008)

3.1 Contingent valuation method

Contingent valuation method is a choice-based approach to ask the individual how much they are willing to pay for specific good with certain set of attributes and levels In

some cases, they are also asked the amount they will accept in compensation to give up a specific one It is called “Contingent” valuation, because people are asked to state their willingness to pay, contingent on a particular hypothetical scenario and description of the commodity being valued The CVM approach estimates the good for a whole

The survey was created with the hypothetical good constructed by the relevant attributes and levels, and this was presented with different prices The range of price was chosen with assumptions that most people agree to pay at the lowest price and that most everyone would reject the highest price

The survey will be started with average price to be offered to respondent, if it is was rejected, then the lower price will be offered until respondent agree with that price or until the lowest price was rejected Otherwise, the higher price will be offered until the highest price or respondents reject the offer

The CVM has been applied with varying degrees of success in health care both for benefit valuation and for elicitation of public view As monetary benefit valuation is increasingly advocated in health care and many methodological issues become better understood, the use of CVM for valuing the multiple-dimension of health care benefits can

be expected to grow (Ryan M et al., 2008)

3.2 Discrete choice experiment

The DCE is an attribute-based survey method for measuring benefits (utility) which respondents are presented with the samples of hypothetical choice sets The choice sets comprise two or more alternatives which contain the combination of attributes of goods/service with various levels Respondents will make the trade-offs between attributes levels by choosing the alternative with high utility in the choice sets of the survey

The DCE assumes that individuals derive utility from the underlying attributes of the commodity under valuation (rather than the commodity per se) and that individuals’ preferences (as summarized by their utility function) are revealed through their choices

The results from the experiment are used to model preferences within a random utility maximization (RUM) framework (McFadden, 1974)

As with consumer theory, the respondents in DCE are assumed that they are rational decision makers and they seek to maximize innate, stable preferences However, in DCE there are there important extensions:

 Attributes of goods/services determines the utility

 Participants deal with a choice among a set of finite and mutually exclusive alternatives (choose one and only one alternative from this choice set)

 Individual choice behavior is intrinsically probabilistic, hence random

Table 1: Example of choice set of discrete choice experiment design

vaccination

Option 2: Influenza vaccination Effectiveness of influenza

Cost of vaccination (by

Which option you would

choose?

4 Applications of discrete choice experiments in health care

Discrete choice experiments (DCEs) are increasingly used in health economics to address a wide range of health policy-related concerns in figure 2 (Michael D., 2014)

Within 3 years from 2009 – 2012, there are 179 studies, nearly five times more than duration of 10 years from 1990-2000

Figure 2: Average of health-related DCE studies/year DCE in healthcare mostly conducted in UK at the beginning, then it was extended

to USA, AUS, and other countries

Relevant attributes

It is acceptable reality that researchers cannot observer all the factors affecting individual preference, and the more factored included the more complexity required The correct specification of relevant attributes along with their levels are vital role for successful elicitation

Attributes can be quantitative (e.g cost, number of injection) or qualitative (e.g type of healthcare, healthcare service grade), and be generally derived from published literature, textbook, regulatory documents Or new attributes can be collected throughout

a discussion with expert or pilot testing with targeted subject pool

The main domain of attributes in health economic includes money, time, risk, health care, health status For the vaccination preference, the attributes of vaccination derived from literature are: effectiveness, adverse event, cost, number of injection, time, allocation, physician’s recommendation

There is no rule for the number of attributes to be used, but the multiplying increase

of choice sets by number of attributes requires capture the main attribute for majority of respondents Almost studies recruit 4-6 attributes for DEC design

In case the number of possible attributes exceeds which could lead to the potential large design, then rating or ranking exercise could be help for maintaining the important attributes

A sufficiently difference between level should be used to avoid respondents ignoring attributes because the little difference in levels, especially for the choice set designed with two comparing alternatives Unless special required, it does not need span the full spectrum of levels For example, we may not use the longest time of waiting in describing the level for attribute of waiting time Instead, the interquartile range or at plus and minus one standard deviation from the mean can help Number of level is usually limited to three or four per attribute and the same pace between levels is not required

Discrete choice experiments design

The experimental design is the combination of the attributes with levels used to construct the alternatives included in the choice sets

A full factorial design includes all possible combinations of the levels of the attributes and allows for estimation of main effects and interaction effects

A main effect refers to the direct effect of each independent variable (the difference

in attribute in attribute levels) on the dependent variable (choice variable) An interaction

effect is the effect of the interaction between two or more independent variables (by varying two or more attribute levels together) on the dependent variable

For an experiment with k attributes and each attribute q (q = 1, 2 k) defined by lq levels, the total number of possible combinations, L, is given by the product of the number

of levels for each attribute For example, with five attributes (k = 5), two at four levels and three at five levels (often denoted 4253), there are 4*4*5*5*5 = 2,000 combinations

in the full factorial A fractional design was chosen to reduce the complexity of full factorial design which includes the main effects and sometime plus the significant interaction effects

For the construction of choice sets, if a binary choice DCE is used (e.g would you use this service, yes/no) then the scenarios derived from the full factorial or fractional factorial design are the choice If two or more alternatives are employed the scenarios must

be properly placed into choice sets

And to minimize the number of choice sets required for each respondent, the choice sets could be blocked into parts and randomly assigned when implementing

The main objectives of design are identification and efficiency, while the identification is priority before constructing the design The identification is referred to the effects included in the indirect utility function, which requires the chosen relevant attributes and levels, with the model of main effects and/or interactive effects The identification cannot be changed once a design is constructed, while the efficiency could be improved by increasing the sample size

Efficiency is related to the precision with which the effects are estimated In this respect, proposed desirable design criteria that are orthogonally (attribute level appear with equal frequency with each level of each other attribute in all the included alternatives), level balance (the levels of each attribute in appear with equal frequency in all the included alternatives), minimal overlap (there are as few overlaps of levels as possible for each attribute in each choice set) and utility balance (the options in each choice set should have

similar probabilities of being chosen) The orthogonality is most important character for design

The variance-covariance matrix (i.e det(C-1)) was used to compare different design,

in which the optimal design will have the smallest value of det(C-1) or largest value of det(C), we called it as det(Copt) With the comparing design of Cd, the D-efficiency of design

is given by:

D-efficiency= with p is parameters to be estimated

The researcher could use the orthogonal main arrays, or software package (such as: SPSS, SPEED, SAS) to get the design with D-efficiency score

Model estimation

If the choice set includes binary choice (yes/no) or only two alternatives, then binary probit or logit model are appropriate Both models, binary probit and logit, lead to equivalent parameter estimates up to scale

If the study collects multinomial rather than binary choice data, the alternative model estimation was developed with start using the McFacdden’s multinomial logit (MNL) The MNL has four important assumptions: (i) identically distributed errors (i.e., constant error variance or homoscedasticity); (ii) independent errors (i.e., independence of irrelevant alternatives (IIA); thus assuming that all options are equal substitutes); (iii) no panel data (i.e., no correlation allowed for within responses); and (iv) no taste variation (i.e homogenous preferences across respondents)

Three alternative families of models which were developed to relax the restrictions of the McFadden’s MNL model (Ryan, M et al., 2008): (i) the heteroscedastic model, which relax the assumption of identically distributed errors; (ii) the generalized extreme value (GEV) models, which relax the assumptions of independent errors and allow for random taste variation (MNL, GEV, and heteroscedastic models allow for heterogeneous preferences using sub-group analysis; the key contribution of the flexible models is that

sub-goups do not have to be identified in advance, the data does this) and for multiple observations as well (e.g., mixed logit model (MXL) and latent class model (LCM)

Validity issues The validity tests for respondents’ responses are stability, transitivity, monotnocity and compensatory decision making, among those, transitivity and stability are most important

Transitivity requires that if treatment A was preferred to Treatment B and treatment

B was preferred to treatment C, then treatment A should also be preferred to treatment C for same respondent This validity to assure the logical preference through the perception

of alternatives

The monotonocity refers to the validity of attribute levels, it requires the advantage

of attribute level should be remained (e.g.: if treatment A and treatment B are identical in all attributes but cost attribute level of treatment A is lower than treatment B, then treatment

A will be chosen)

The stability requires the same response for the repeated choice set (i.e if respondent chose treatment A than B previously, then it should be remains if that task was asked again in the survey)

Compensatory decision making assumes that the respondents can be compensated for a decrease in one attribute with an increase in the other attribute, involving that the respondent is willing to trade off the attributes This validity is depended on the individual perception, and also the priority of attributes, so it is quite difficult to assess

In cases of failure for axioms, the argument was raised to remain or remove from the analysis San Miguel et al (2005) and Ryan et al (2009), both using qualitative research techniques, found that individuals who had been defined as failing non-satiation from quantitative tests, had ‘rational’ reasons for doing so Lancsar and Louviere (2006) also noted that random utility models are robust to both violations of compensatory decision making and errors made by individual in forming and revealing preferences Deleting such respondents may therefore result in the removal of valid preferences, which in turn may reduce statistical efficiency and/or result in sample selection bias Furthermore, even if respondents are not trading, and marginal rates of substitution cannot be estimated, these preferences are still important from a policy perspective (Lancsar and Louviere, 2006)

5 Discrete choice experiment application in healthcare, Viet Nam

Until now, there are 2 of DCE studies conducted in Viet Nam for healthcare was identified Both of them was preference for vaccine, including HPV, typhoid, cholera

Domain of DCE attributes mainly focus on money, time, risk, health status Among that, monetary is interesting topic in healthcare policy, but it is still too high as the common issue of DCE

In 2002 – 2003, JOSEPH C et al has conducted the DCE in two sub-samples for cholera, typhoid vaccine in Hue province, Viet Nam Both subsamples answered the same questions, but one subsamples was given more time to review and answer (having time to think), other subsample was asked to completed choice tasks (no time to think) Respondents who were given extra time made fewer choices that violated internal validity tests of utility theory, and had lower average willingness to pay (WTP) And in 2009, Christine Poulos a, et al has conducted for HPV vaccine in Vinh Long, Viet Nam, and the

highest price was considered to be set a bit too low, which may cause the tails of the distribution of estimated WTP are larger and WTP estimates are inflated

The validity test was included in the HPV vaccine study to examine the quality of respondents’ response to choice question Firstly, choice set with superior vaccine in all of attributes to other primarily evaluates the awareness of attributes and levels The majority

of respondents (84%) chose the superior vaccine in this section Secondly, to assess the consistency, the one choice set was repeated The 19% of sample failed this consistency test Finally, study also examined whether respondents had dominant preferences for one

or more attributes Sixty-three respondents (21%) had dominant preferences for risk reduction, 14 respondents (5%) had dominant preferences for duration of protection, and

105 respondents (35%) had dominant preferences for vaccine cost

6 Discrete choice experiment application in seasonal influenza vaccine

Shono A and Kondo M have used the DCE to investigate the parent’s preferences for seasonal influenza vaccine for their children in Japan

In Japan, trivalent inactivated influenza vaccine which administrated by hypodermic injection, and children under 13 years of age, and new live-attenuated influenza vaccine which is administrated by a thimerosal-free nasal spray Seasonal influenza vaccine for children is voluntary

The refined list of attributes and levels:

Table 2: Attributes and levels of influenza vaccine in Japan

Vaccination price for one winter

season

0; 2000 yen; 3500 yen; 5000 yen

6500 yen; 8000 yen; 10,000 yen

Times of vaccination for one winter

season

One time Two time

Vaccine effectiveness in decreasing

risk of influenza infection

25%; 50%; 75%; 99%

Risk of adverse events 10%; 5%; 1%; 0%

Injection avoid Yes (Nasal spray); No (Injection)

The Thimerosal is a mercury-based preservative and has been used in some vaccines

to prevent the growth of bacteria and fungi contamination Beside the international discussion about thimerosal-containing vaccine, it was considered the Japanese background, which includes Minamata disease, caused by catastrophic environment pollution due to methylmercury passion in Japan

It was used a library of orthogonal arrays to generate 36 combinations, and each choice sets including two random combinations and opt-out option The questionnaire also includes the respondents’ demographic: age, gender, education, marital status, number of children, annual household income, history of seasonal influenza, and adverse event The description of the attributes and their levels were described, with sample images Each respondent will answer 5 choice sets for DCE part The pilot test was done to check the understanding and refine the questionnaire The respondents were recruited online to complete the questionnaire

Results derived from DCE were analyzed using a conditional logit model, with and without interaction For interaction effects, a dummy variable was used for “neither vaccination” for each DCE question

Respondents were significantly more likely to choose profiles with fewer times of vaccination for each winter season, higher vaccine effectiveness, lower risk of adverse events, thimerosal-free vaccines, and lower vaccine price There was no significant preference for injection avoided (nasal spray versus injection) For interaction between

“opt-out” option and attributes and demographic, it shows the older and women are more likely to prefer no vaccination

The willingness to pay for an improvement in an attribute of seasonal influenza vaccination

Table 3: Willingness to pay for influenza vaccine in Japan

CHAPTER 3: RESEARCH METHODOLOGY

This chapter is to present the construction of survey and the data collection As mention, the discrete choice experiment was chosen as the approach for data collection beside the individual characteristics

To construct the survey, the list of all influencing factor derived from literature review was used for reviewing and shorting into the priority list From this selected lists, the socio-economic and history were designed as the question list for data collection Otherwise, the attributes of vaccine was reviewed and advised by vaccine expert for relevant levels, before it was designed by SPSS software with orthogonal method

The survey consist there parts: socio-economic and history of respondent, introduction of influenza and vaccine, discrete choice experiment

The survey will be sent to respondents who is working adults, by hard copies and self-completed one to be returned

1 Discrete choice experiment methodology

It starts as the research objectives to identify the relevant and targeted attributes and levels The attributes and levels are derived from literature review, expert’s advice and survey if needed The discrete choice experiment construction was conducted by different method to create alternatives The construction plays the key role for quality of data collection, requires more effort and attention to generate the discrete choice experiment, it could be combined with other section to be final questionnaire The questionnaire will be used for survey to collect data before analysis

Attributes and levels Discrete choice

Pilot survey

Final questionnaire Research objectives

Survey/data collection Model estimation

2 Discrete choice experiment construction

2.1 Identification of relevant attributes

The selection of attributes along with their levels which influence choice, determines the ability of model to capture the systematic component of utility The long list of attributes was identified by starting with literature review

The list of factors which impacts the acceptance of influenza vaccine includes seasonal or pandemic influenza among ages was identified from reviewing the published articles (Vasilevska M et al., 2014) (Wheelock A et al., 2013) (Stephanie B et al., 2012) (Bonfiglioli R et al., 2013) (Castell A et al., 2009) (Ganczak M et al., 2013) (Porter CK

et al., 2013) (Stafford KA et al, 2013) (Frew PM et al., 2011) (Lu PJ et al., 2011) (Middleman AB et al., 2012) (Abu-Gharbieh E et al., 2010) (Blank PR et al., 2009) (Blank

PR et al., 2008) (Li Z, Doan Q and BobSon S., 2010) (Marentte T, El-masri MM., 2011) (Wiese-Posselt M et al., 2006) (Liu S et al., 2011) (Kee SY et al., 2007) (Nagata JM et al., 2013)

The list attributes was discussed with experts to identify or revise the term for investigation further

Table 4: Primary list of characteristics and attributes influencing choice of influenza

vaccination

Category Descriptions

Socio-economic

Age Having child Being a doctor Education High income Health insurance coverage Lack of time

Immigrant History of influenza infection Healthy enough not to be in need for vaccination Vaccination in prior seasons

Respiratory chronic illness

Vaccine

attributes

Adverse event Vaccine effectiveness Awareness of vaccination Self-protection

Preventing both influenza and common cold Avoid the spread of influenza to others Availability of vaccine

Convenience of vaccination (time and avenue) Cost of vaccine

Disease

Risk of infection Seasonal influenza time Complication of influenza infection

Others Working absenteeism

Reference from friend

The list attributes was discussed with experts to identify or revise the term for investigation further:

Socio-economic

For “being doctor” was extended to “working in the health-relating company or not”, to be more feasible to targeted participants Currently, the influenza vaccination is not covered by insurance, and it could be paid by individual or by company So, the insurance factor will replaced by “paid by pocket or company”

“Lack of time” should be addressed by “Convenience of vaccination (time and avenue)”

The attributes of “immigrant” is very small proportion of Vietnamese, it was considered to remove from model

“Healthy enough not to be in need for vaccination” is ambiguous term and not directly to the influenza infection’s characteristics than respiratory chronic ill So, the inclusion of this term could increase the complexity of questionnaire rather than the benefit

Otherwise, experts recommend to include the marital status However, other reports have found no relationship of marital status with vaccine uptake (Nagata JM et al., 2013)

Vaccine attributes

“Self-protection” and “preventing both influenza and common cold” are the general effectiveness of vaccine, were covered by “vaccine effectiveness”

“Availability of vaccine” was not applicable for this model, in which it is assumed

to ensure the supply of vaccine

Disease

Generally, the risk of infection in working adult is 5-10%, but the perception of influenza infection risk is depended on the individual So, these characters can be covered by: history of influenza

Others

Patient who are at the high-risk of influenza and recommended by doctor nurse will mostly accept the vaccination, so this population is significant different from other population, and highly correlate to vaccination up-take Instead of the reference from friend could be replaced

Table 5: Secondary list of attributes influencing influenza vaccination up-take

Category Descriptions

Socio-economic

Age Having child Working in the health-relating company or not Education

High income History of influenza infection Vaccination in prior seasons Respiratory chronic illness

Vaccine

attributes

Adverse event Vaccine effectiveness Awareness of vaccination Avoid the spread of influenza to others Convenience of vaccination (time and avenue) Cost of vaccine

Disease Seasonal influenza time

Complication of influenza infection

Others Working absenteeism

Reference from friend

The questionnaire consists of two parts, one is demographic, and other is actual discrete choice experiments (or choice sets)

The number of attributes and level will define how many choice set will be created for design, but the size of experimental design increases by multipliable with number of attributes and exponentially with the number of levels Even for a small factorial design (e.g three attributes at four levels, i.e 4*4*4 = 64) this can amount to a much larger

2.2 Selection of attributes

From above secondary list, the factors were considered to be used for first part or for DCE model The literature review for the DCE in health-care reports the number of attributes are mostly from 4 to 6 as figure 4 (Michael D et al., 2014)

Figure 3: Number of attributes The list of ten attributes which was retrieved from above list was tested for the influence to the vaccination decision A survey with 41 respondents were collected (Appendix 1) The results from survey was analyzed by t-test

The scale of importance/influence is range from 1 to 5: 1-Totally not impact; 2- Very low impact; 3-Neutral; 4-Significant impact; 5-Definitely impact

Table 6: Result of survey for influencing attributes

Ha:

mean

!= 3 (Pr (T<t))

Ha: mean >

3 (Pr (T<t)) Adverse event 40 3.325 0.210 1.328 2.900 3.750 0.9351 0.1297 0.0649 * Effectiveness of

vaccine 41 3.951 0.171 1.094 3.606 4.297 1 0 0*** Awareness of

vaccine 41 3.366 0.184 1.178 2.994 3.738 0.9732 0.0536

0.0268

** Avoid the spread

of influenza to

others 41 3.878 0.145 0.927 3.585 4.171 1 0 0*** Convenience 41 3.220 0.183 1.173 2.849 3.590 0.8811 0.2378 0.1189 Cost of

vaccination 39 3.128 0.181 1.128 2.763 3.494 0.7589 0.4822 0.2411

Seasonal disease 39 3.692 0.165 1.030 3.358 4.026 0.9999 0.0002

0.0001

*** Complication of

influenza

infection 41 3.268 0.156 1.001 2.952 3.584 0.9531 0.0937

0.0469

** Working

absenteeism 41 3.195 0.168 1.077 2.855 3.535 0.8734 0.2531 0.1266 Reference from

friend 37 2.946 0.160 0.970 2.622 3.269 0.3683 0.7367 0.6317

***: p<0.01, **: p<0.05, *: p<0.1

The “reference from friend” and “working absenteeism” with lowest p (0.1266 and 0.6317) were not included in model For the “cost”, the p=0.2411, it suggest that cost does not impact on the vaccination decision, it was proved in the final result of this model (find

in chapter 3) The rest of attributes were considered to add in the model

There are many studies to indicate the efficacy/effectiveness vary arrange from 70%–90% of healthy adults aged <65 years Because the variation from season to season and the circulating strains, so the systematic review of studies cross-over some season will

be used Osterholm and colleagues meta-analysis (across consecutive seasons 2004-2008) estimated a pooled inactivated vaccine effectiveness against influenza infection in adults

of 59% [95%, CL 51-67], compared with estimated effectiveness of 62% [95%, CL 56-67] (20 studies included from 1969-2011) reviewed by Cochrane Collaboration (Demicheli V

In this thesis, the mild AE was used with definition from the vaccine information statement (2014-2015) from Center for Disease Control: (Anon., 2014)

Mild problems following inactivated flu vaccine:

 soreness, redness, or swelling where the shot was given

 aches

 headache

 itching

 fatigue

If these problems occur, they usually begin soon after the shot and last 1 or 2 days

Note: The adverse events caused by the quality of vaccination (such as health care

staff’s qualification, the violated storage condition, or impaired process) was not included

Placebo-controlled trials demonstrated that the administration of TIV is not associated with the higher rates for systemic symptom compared with placebo injection (35.2% of placebo and 34.1% of vaccine recipients reported at least 1 of systemic symptoms) (CDC, 2010 ) In another observational study in Russian healthy working adults (O Yu At’kov et al., 2011), the systemic symptoms are a general feeling of being unwell (4.3%), headache (3.3%), runny nose (3%) and tiredness (2.9%) In double-blind, randomized study, with 7611 adults (18-49 year-old) participants, the adverse events report for the TIV injection versus placebo injection: pain at the injection (51% versus 14%), tiredness (20% versus 18%), and myalgia and/or arthralgia (18% versus 10%), fever (Oral temperatures of >=37.5oC) (3% versus 1%), and pharyngolaryngeal pain (both 3%), headache (both 3%), fatigue (both 3%) ( Jackson et al., 2010)

The risk of adverse event of influenza vaccination was used from 0-10% in the discrete choice experiment study titled “Parents' preferences for seasonal influenza vaccine for their children in Japan” (Shono A, Kondo M, 2014) The range of 0-10% AE was also accepted by vaccine expert as well The levels of “adverse event” attributes was used as: 0%, 5% and 10%

Complication of influenza infection, awareness of vaccine, communicability of influenza, seasonal disease

The study used a test-negative approach to estimate influenza vaccine effectiveness (IVE) of 33% [95%, CL 11-49%] against hospitalization with laboratory-confirmed influenza based on data collected from the Global Influenza Hospital Surveillance Network