Università degli Studi di Pisa
Scuola di Dottorato “G. Monasterio”
Programma: “Fisiopatologia medica e Farmacologia”
Decano Chiarisimma Prof.ssa Maria Cristina Breschi
La Qualità della vita come dimensione non ignorabile nelle valutazioni cliniche
ed economiche: un’applicazione nell’ambito della chirurgia bariatrica
(Quality of Life in clinical and economic evaluation: the case of bariatric surgery)
Relatore
Chiar.ma Dott.ssa Monica Nannipieri Tutor
Chiar.mo Prof. Giuseppe Turchetti
Dottorando
Chapter 1.
Quality of life: an overview and concepts
1.1 History of Quality of Life 5
1.2 The concept of Quality of Life 9
1.3 Health Related Quality of Life 15
1.4 Areas and dimensions of Health Related Quality of Life (HRQoL) 18 Chapter 2.
Health Related Quality of Life in research
2.1 Measuring Quality of Life and Health Related Quality of Life 21 2.1.1 Instruments for Quality of Life assessment 21 2.2 The process of developing Quality of Life instruments 24 2.3 Psychometric requirement of a Quality of Life instrument 27 Chapter 3.
Generic and disease-specific health related quality of life instruments
3.1 Generic Health Related Quality of Life Instruments 30
3.1.1 Valuing Health Related Quality of Life 30
3.1.2 The World Health Organization Quality of Life
Questionnaires: WHOQOL-100 and WHOQOL-BREF 33
3.1.3 The European Quality of Life Instrument: EuroQoL-EQ-5D 36
3.1.4 Health Utility Index: HUI 37
3.1.5 RAND/MOS SF-36 Item Health Survey 39
3.2 Disease specific Instruments 46 Chapter 4.
Obesity facts
4.1 Obesity: context and epidemiology 48
4.2 The economic impact of obesity 51
4.2.1 Direct Costs of Obesity 53
4.2.2 Indirect Costs of Obesity 53
4.3 How to manage obesity 55
4.3.1 Non-surgical treatments 56
4.3.2 Bariatric surgery 57
4.4 The economic impact of bariatric surgery 64
Chapter 5.
Health Related Quality of Life and obesity
5.1 Quality of life among the general obese population 66
5.2 HRQoL obesity-specific instruments 68
5.2.1 IWQOL/IWQOL-Lite 69
5.2.2 The Obesity-Related Problem Scale (OP) 71
5.2.3 The Obese Specific Quality of Life (OSQOL) 71 5.2.4 The Bariatric Analysis Reporting Outcome System (BAROS) 72 5.2.5 The Obesity and Weight-Loss Quality of Life (OWLQOL)
instrument 75
6.1 Introduction 80 6.2 Prospective evaluation of HRQoL following bariatric surgery:
a systematic review of the literature
6.2.1.Methods 81
6.2.2 Results 83
6.2.3 Conclusion 95
Chapter 7. A case study
7.1 Rationale and brief description of the study 99
7.2 Study Design 100
7.3 Subjects 102
7.4 Data collection 103
7.4.1 The questionnaire for data collection 104
7.4.2 Study database 110
7.5 Methods
7.5.1 Quality control of data collected 111
7.5.2 Statistical analysis 111
7.5.3 Path analysis for the identification of the determinants of
Quality of Life 112
7.5.4 Methods for the identification of subjects with poor outcome:
two steps cluster analysis and prediction tree model 115 7.5.4.1 Two-steps cluster analysis for the definition of outcome 115 7.5.4.2 Prediction tree models for outcome evaluation 116
7.6.2 Follow-up data 128
7.6.3 Costs 140
Table 3.1 Exemplification of the difficulties in using preference-based measures in health economic evaluation
Table 6.1 Main characteristics of studies involved in the analysis
Table 6.2 Factors associated with HRQoL post surgery using simple decsriptive analysis
Table 7.1. Clinical centres involved in the study by region Table 7.2. Distribution of subjects enrolled by centre
Table 7.3. Number of subjects (percentage) by bariatric procedures among the different centres
Table 7.4. Baseline characteristics of enrolled patients by surgical procedure Table 7.5. Baseline SF-36 scores by surgical procedure
Table 7.6. One-year change in SF-36 scores by surgical procedure
Table 7.7. Univariate regression analysis of %EWL, MCS and PCS changes at 12 months
Table 7.8. Outcomes variables according to clusters identified in the two-steps cluster analysis
Table 7.9. Prediction tree for the combined outcome
Table 7.10. Median [25-75 percentile] health direct costs (in Euro) for the different evaluation time by surgical procedure
Table 7.11. Results from the multivariable analysis of health direct costs (in Euro) for the different evaluation time; adjusted* coefficient (Std.Err.) and P-value for the different procedures
Figure 3.1 Sample page of the 15D questionnaire
Figure 3.2 Sample page of the Nottingham Health Profile (NHP) Part I Figure 3.3 Sample page of the Nottingham Health Profile (NHP) Part II Figure 4.1 Prevalence of overweight in 2008
Figure 4.2 Prevalence of obesity in 2008 Figure 4.3 Roux-en-Y-gastric bypass (RYGB) Figure 4.4 Adjustable Gastric Banding (AGB) Figure 4.5 Biliopancreatic diversion (BPD) Figure 4.6 Sleeve Gastrectomy (SG)
Figure 5.1 Sample page of the Impact of Weight on Quality of Life-Lite Questionnaire (IWQOL-Lite)
Figure 5.2 Sample page of the Bariatric Analysis Reporting Outcome System (BAROS) I instruments containing the M-A QoLQ
Figure 5.3 Sample page of the Bariatric Analysis Reporting Outcome System (BAROS) II instruments containing the M-A QoLQ II
Figure 5.4 Sample page of the Obesity and Weight-Loss Quality of Life (OWLQOL) instrument
Figure 6.1 Study selection process
Figure 7.1. Front page of the ad-hoc questionnaire used in the study
Figure 7.2 Demographic section of the ad-hoc questionnaire used in the study
Figure 7.3 Socio-economic section of the ad-hoc questionnaire used in the study (patient section)
Figure 7.4 Socio-economic section of the ad-hoc questionnaire used in the study (caregiver section)
Figure 7.8 Prediction tree of total health care costs (values in $ at each terminal nodes or leaves) according to the combination of disease classification (CCS) and demographic variables (age and geographic area)
Figure 7.9 Mean %EWL for different bariatric procedures
Figure 7.10 Mean PCS (a) and MCS (b) score over time by surgical procedure
Figure 7.11 Correlation between %EWL and SF-36 changes from baseline to 12 months
Figure 7.12 Path diagram
Figure 7.13 Classification tree for the Composite Outcome
Figure 7.14 Percentage of health direct costs associated to pre-surgery evaluation by cost components and surgical procedure
Figure 7.15 Percentage of health direct costs associated to surgery by cost components and surgical procedure
Figure 7.16 Percentage of health direct costs associated to the immediate post-surgery by cost components and surgical procedure
Figure 7.17. Direct health costs for the different evaluation times according to clusters identified in the two-step cluster analysis
Figure 7.18. Direct non-health and indirect costs for the different evaluation times according to clusters identified in the two-step cluster analysis
Quality of life (QoL) is a broad term used to generally define a situation of “happiness”, “well-being” or “liveability” intended in the more general view of the term. QoL is used in a wide range of fields (economy, sociology, psychology, medicine etc.) encompassing all the different concepts embedded in the term.
The term quality of life assumes particular relevance in the context of medicine where, usually called Health Related Quality of Life (HRQoL), it has gained increasing attention in the last decades being evaluated at the same time as an additional indicator of outcome/effectiveness but also as a possible determinant of it. The recent definition of quality of life given by the World Health Organization (WHO) is expressed as “a state of complete physical, mental and social well-being not limited to the sole absence of disease”.
This definition covers several dimensions related to the individual including, among the others, physical, mental and social domains.
The increasing relevant attention grew on quality of life during the last decades is due to the recognition that it strongly impact on the daily life of individuals; moreover and among patients it plays an important role in disease progression and recovery as well as in resource consumption.
Particularly several recent works i.e. People 2000, 2010, 2020 outlined that quality of life is not only related, and influenced, by chronic disease but it also represents a risky condition for development of unhealthy living.
Moreover as medicine and treatments progressed it became clear that the sole evaluation of life saved could not serve as whole measure of outcome or effectiveness, by adding quality of life it is possible to comprehensively evaluate interventions and treatment options also explaining possible differences among subgroups of people and target specific intervention tailored to improve effectiveness both in terms of health gain and on quality of life gained.
In a context in which new models of intervention and treatment, as well as the introduction of new technology in the health care sector, need to be based on proof
HRQoL as additional measure of outcome need to be incorporated in all the evaluation.
If this tendency began in the last decades, the theme of QoL has never been so crucial as it is now and this is confirmed by priorities launched by most European and international health policies.
Particularly among the key strategies identified by the European Commission in the context of health, QoL appears in quite all messages.
In summary four main reasons explained the reason why HRQoL represents a priority in the evaluation of intervention or treatment and they could be summarized as follows:
• Independently from the intervention, HRQoL gives unique and useful
information about the real impact of the disease on the patient;
• Success of a certain intervention could be evaluated by means of objective
physiological parameters but the real benefit of it could only be assessed measuring patient’s well-being and his/her ability to perform usual activity in daily life;
• The use of HRQoL as additional outcome measure in clinical and health
economic evaluations gives centrality to patients’ need;
• Finally the use of HRQoL in health economic evaluations guide the adoption
of strategies and the allocation of interventions trying to maximize the benefit for the all society.
Given these premises, in the present thesis the importance of HRQoL will be stressed and analysed with respect to a phenomena that has gained enormous attention in the last decades, representing one of the major public health problem in the world, obesity.
Obesity is a chronic condition with complete recover being highly unlikely and for such a reason measure such those related to QoL represent valid alternative health outcomes to be considered in the management of the disease.
Moreover given the proportion that the phenomena reaches in recent years and the recognized impact of obesity on quality of life, the use of HRQoL as a necessary end-point in the treatment of obesity need to be considered.
Anyway, despite a certain degree of consensus around the importance of HRQoL outcomes in the treatment of obesity still exists, efforts have been quite limited in the development of standardized methods for the systematic introduction of HRQoL as outcome measure in the treatment of obesity. As a consequence the effect of bariatric surgery is still not clear.
The primary objective of this thesis is thus to propose statistical methods to evaluate the determinants of HRQoL and to perform an integrated evaluation of outcome in bariatric surgery showing results of the adaptation of the above mentioned methods on real data, with the aim of offering instruments and evidence that could be easy translated into clinical practice but that could be also useful for health economic evaluation.
As secondary objectives this work aims at overviewing the available instruments for HRQoL assessment and perform a systematic review of the literature concerning the effect of bariatric surgery on HRQoL.
To do this the work is articulated in subsequent logical steps guiding the reader on the process of the development of the main objective and sub-objectives of the present work.
Particularly after offering a general overview of the concept of QoL and its measurements, to get the reader the necessary elements to understand the framework of QoL, HRQoL and the way they are assessed and used in research, the attention is then posed on the context of obesity in order to, after introducing general facts about epidemiology, economy and treatment of obesity:
• perform a recognition of the available generic and disease specific
instruments for HRQoL to offer clinicians, health economist and different researcher profiles interested in a range of instruments validated and currently used in general clinical research and in obesity to guide them in the use of these instruments into future study but also to plan the development of novel instruments overcoming limits of the present one (particularly in the case of disease specific instruments);
• perform a literature review concerning the effect of bariatric surgery on
• using real data and the background gathered from the literature review, to
examine the determinants of HRQoL, its relation with clinical outcome in a prospective multicentre study involving patients submitted to Gastric Bypass, Gastric Banding and Sleeve Gastrectomy thus allowing also for comparison among different procedures, identify a “combined outcome” including physiological parameters as well as HRQoL data to be used in further predictive model in order to identify characteristics of patients that could be predictive of good outcome;.
• and finally, offer an assessment of the economic impact of bariatric surgery
Chapter1
Quality of life: an overview and concepts
1.1 History of Quality of Life
Generally speaking when thinking about quality of life several concepts concerning different fields come into one's mind: good physical health, happiness, well-being, income, etc.
In fact quality of life is a multidimensional term involving, among the others, also the concepts above.
Anyway, giving a general definition of quality of life is still a challenge. As will be discussed in the next paragraph, a lot of debate still exists around an overall definition, with scientists in different fields giving various definitions accordingly to the complex evolution of the debate around the term.
An overview of the evolution of the concept of quality of live will give an idea of the complexity of reasoning around it and the fragmented course of its evolution will explain why, even after many years of reasoning, scientists have not yet reached a general consensus about a common definition of quality of life.
Although the concept of quality of life has gained centrality in the scientific and political discourse only in the middle of the last century, to track the origin of the concept it is necessary to go back to ancient Greek, in the B.C.E. era.
Some scientists track in the work of Humerus and in the theories of philosophers in the B.C.E. period the early notions of modern QoL.
The profile of humerus heroes, physically strong, able to adapt and to fight against all life obstacles, embody some of the concepts that are typically associated with the prerequisites of good quality of life today.
More commonly is in the work of Plato and his student Aristotle that scientists dated back the origin of the modern quality of life concept.
He considered harmony as the general prerequisite for both individuals and society. He argued that a society in which individuals were always in conflict with each other would be unliveable as opposed to a society in which individuals lived in harmony. Similarly he viewed the peace of a good life for an individual as harmony of reason and passions (Sirgy MJ et al. 2006).
Individual and society concepts of quality of life were further refined in the work of Aristotle that defined his view of “good life” and “living well” in the doctrine of social ethics and perfect society.
Indeed Aristotle postulated happiness as the proper intrinsically valuable end for humans and viewed the way to be happy in “living and doing well” embedding in this definition not only feelings, attitudes or belief, but also comprising all subjective and objective indicators commonly used today (Sirgy MJ et al. 2006)
Other precursors of the modern theories about quality of life are recognized in Aristippus and the Epicures that further elaborated the concept of happiness and are considered, together with Aristotle, as the first theorists of the subjective dimension of quality of life. It is in fact attributed to Aristippus the hedonic view that is the maximization of pleasure as the scope of life and the source of happiness.
Despite this ancient theorization of the quality of life concept, further evolutions and refinements that have led to the actual development and centrality of the concept in many fields are dated to the second half of the twenty-century. In this period the definition of quality of life evolved parallel in different disciplines, particularly economists and political scientists firstly conveyed their attention on quality of life being interested mainly in its material dimension.
In fact, following the rapid structural changes of societies, in this period there was a great interest in measuring the level of material wealth reached by individuals so that several efforts were made in finding measures able to capture the quantity of well-being.
The material level of living dominated this phase of development of the quality of life concept following the general belief that higher that level in a country and in individuals, the better the life was presumed to be. In such context the Gross National Product (GNP) and related indices, similar to the currently “real” Gross
Domestic Product (GDP) per head, were developed and used as measure of quality of life.
Although this material dimension is still embedded in the “overall” quality of life concept, after the initial enthusiasm in this view, soon the limit of a poor materialistic conception of quality of life emerged prominently.
Particularly in the 1960's, the limits of economic growth came in view and the implication “good level of material health-good level quality of life” became to be questioned.
In this climate thus developed the sociological view of quality of life.
With the social indicators movement sociology gave an important contribution in both the refinement of the term and consequently in the way of measuring and valuing quality of life using social indicators. The social indicators movement is dated approximately to the first half of the twenty-century and refers to the effort made to develop and produce statistical measures able to capture an objective definition of the condition of modern society going beyond the mere economic assessment. From its beginning, one of the aims of Social Indicators Research movement was to develop a social equivalent to the economist's GNP and several measures have been proposed since.
The principal inputs for the development of the movement could be found in the USA. and in north Europe. Following the relevant structural change that invested societies in those years both scientist and governments were interested in understanding how these changes impact on individuals and on the society in general, not only in economy.
In fact it was just an economist that pointed out the need for more general indicators able to inform public policy about social problems and offering “insight into how different measures of national well-being are changing” in order to offer a better understanding of the effects of public programs. The pure economic “conceptualization” of quality of life was thus enriched by means of social indicators such as occupation, race distribution, education, voting, fertility and so on and thus a set of more complex measures started to be considered.
exploring and defining the societal dimension of quality of life, so pertaining the environmental dimension, psychologists offer a deeper insight into what can be considered the pure subjective dimension of quality of life.
The subjective extent of quality of life rose around the theory of subjective well-being. This concept developed at the end of the last century and enriched the dimensions around which evolved until this time the concept of quality of life just by adding the individual sphere. Subjective well-being refers to personal of satisfaction with life in general or with a particular aspect or dimension of life (i.e. work, private relationship) and involves affective and cognitive components. These encompass the on-going evaluations of current life experience, positive experience as well as an overall assessment of individual's life. The subjective well being has often been linked to the concept of happiness as it was developed by the ancient philosophers, in fact it refers to the satisfaction of personal needs, to the way individuals perceive, adapt and cope with life experience.
This brief summary illustrates the fragmented evolution of the theory about the concept of quality of life and offers an idea of the multiple areas involved in the concept thus providing a minimal background for a deeper insight into the problem of the definition of quality of life that is the topic covered in the next paragraph. Before shifting to the definition of quality of life it is necessary to remark the fact that the brief historical excursus above do not mention extensively an important area of development that is the one related to health. Medicine and public health have and have had central role both on the development on the concept and on the increasing importance that quality of life has gained over years. This area that is also the centre of the present work will be more deeply discussed in a separate paragraph when covering the topic of health-related quality of life, before that it could be just sufficient to remark that in addition to the areas covered before the one of medicine and health in general also conveyed in the comprehensive evolution of the quality of life theory.
1.2 The concept of Quality of Life
Quality of life is frequently referred as a broad and multidimensional term. As could be easy understandable from the historical overview of the development of the QoL concept given in the previous paragraph, several definitions have been proposed in different disciplines but none of these seems to be completely satisfactory. Although generally speaking quality of life is often defined as a synonymous of happiness, well-being, wellness, liveability etc. in their more general idea, none of these terms is able to capture the whole concept embedded in the general definition of quality of life.
In particular, each of these terms could be able to describe a particular aspect of quality of life, that could be the hedonistic, economic and social dimension, but none of them capture the full core of dimensions and interrelationships involved in the whole concept. The multi-faced nature of quality of life is the result of its evolution in the context of different disciplines, each of which, as outlined in the previous paragraph, developed its own definition.
Given this premise, the best way to render the idea of what quality of life means in its general definition is to explore the multitude of definitions proposed over years in the different fields. Just to offer an example of the plethora of definitions developed over years, some of these - particularly those proposed in the recent decades and that have been more commonly used - are listed below:
• The social well-being enjoyed by people, communities and their society (Bach M et al. 1996);
• Is both objective and subjective, involving material well-being, health, productivity, intimacy, safety, community and emotional well-being (Cummins R. 1997);
• A multidimensional concept involving personal well-being. Is concerned with intimate relationships, family life, friendships, standard of living, work, neighbourhood, city or town of residence, the state of the nation, housing,
• Is experienced when a person's basic needs are met and when he or she has the opportunity to pursue and achieve goals in major life settings (Goode D. 1988);
• An emphasis on promoting general feelings or perceptions of well-being, opportunities to fulfil potential and feelings of positive social involvement (Goode D. 1997);
• The multidimensional evaluation, by both intrapersonal and social-normative criteria, of the person–environment system of the individual (Lawton MP 1991);
• The discrepancy between individual's unmet needs and desires. Referring to the subjective or perceived as well as objective assessment. Relates to all life domains. Recognizes interaction between individual and environment (MacFarlane C et al. 1989);
• The individual’s achievement of satisfactory social situation within the limits of perceived physical capacity (La Mendola WF et al. 1979);
• Represents the degree to which an individual has met his or her needs to create their own meanings so that they can establish and sustain a viable self in the social world (Parmenter T. 1988);
• The degree to which an individual enjoys the important possibilities of his her life (Renwick R et al. 1996; Rootman I et al. 1992);
• Person's desired condition of living (primarily related to home and community living, school or work, health and wellness (Schalock RL 1997); • The product of the interplay among the social, health quality, economic and
environmental conditions which affect human and social development (Ontario Social Development Council).
Further broader definitions have been recently developed in the context of the numerous emerging groups of research scientists dedicated to the field. As an example the centre of Toronto defines quality of life as “the degree to which a person enjoys the important possibilities of his or her life”, and the International society for Quality of Life research (ISQOL) defined “HRQOL as the functional effect of a medical condition and/or its consequent therapy upon a patient, HRQOL is thus subjective and multidimensional, encompassing physical and occupational function,
psychological state, social interaction and somatic sensation” (International society for Quality of Life research (ISQOL)).
Even if non-exhaustive, the examples of definitions given above outline that different point of view, and so different disciplines, gave rise to different definition of quality of life just by privileging one or more aspects rather that some others. This is the tricky point of becoming to a general comprehensive meaning of quality of life that is clearly explained by Farquhar (Farquhar M. 1995) that outline the problem related to the different point of view of the various disciplines and also the one, maybe even more complicated, related to the different point of view of different individuals. Particularly Farquhar argued (Farquhar M. 1995) that quality of life is a “problematic concept as different people value different things” and this statement applies both for the subjective point of view of the single individual, but also for the different disciplines. As individuals may attribute different value to the same thing, the same is for scientists with psychologists giving more importance to the subjective dimension of quality of life, sociologists to the environmental context and so on, giving rise to different conceptualization of the term quality of life.
Even depicting a more complicated situation, Farquhar outlined an important aspect of quality of life that has little been discussed until now, the individual dimension. Given the point of view of whatever discipline, what is central in the concept of quality of life is the point of view of the single individual and is just this dimension that elevate the concept of quality of life and that mainly contribute to the importance it has achieved over years in the political discourse and in many field of research. For example It is not uncommon that given a certain equal level of “material well-being” subjects valued differently their quality of life, this could be for past individual experience, for something related to affective life or whatever but it is just to outline that what matter in the definition of quality of life it is both objective and subjective valuation of life.
Quality of life refers to the overall nature of an individual or groups' lived environmental experience, it encompass the satisfaction of material and existential desires and needs (Byrne J. Encyclopaedia of Geography), it means the satisfaction of basic human needs and fulfilment of expectations and depends by personal ability
also by the environment where humans live, i.e. the possibility given in the society. In an ideal world everybody should be able to reach a good quality of life but this is not the case of real world. Subjects are very different each other and societies are not perfect so that both the individual and the policy makers need to put effort to reach a satisfactory quality of life and to give the possibility to individuals to make it available.
Following this reasoning and borrowing ideas developed by some scientists, despite various definitions and the different focus involved, some common point could be identified and extracted to offer a general “meta-definition”.
First of all, even though a comprehensive conceptualization has not been reached, at least scientists in the different fields all recognized the necessity to define a dual dimension of quality of life, one related to objective conditions that individual face with, the other concerning the subjective domain, so that quality of life is the result of the interplay of these conditions that need to be satisfied together to contribute to the objective and subjective existence of the humans.
Using an extreme simplification and adopting the schematization proposed by Venhoveen R. (Venhoveen R. 2000) we could refer to the general definition of quality of life by using two dichotomous dimensions producing the so-called “four quadrants approach”.
The rationale of this analytic tool relies on a classification based on two bi-partitions: between life “chances” and life “results”, and between “outer” and “inner” qualities.
Life chances refer to the possibilities and opportunities offered to the individuals in
their life that could be determined by environmental factors (i.e. the society) and by personal skills referred to the individual ability to take opportunities.
On the other hand life results represent the outcome of the interaction between the opportunity offered to the individuals and the outcome they are able to produce given the ability (individual) and the real possibilities (given by the society) individual actually have.
In fact opportunities and results do not necessarily coincide, chance can not be realized as a consequence of subjects inability or bad luck and, on the other hands, even in front of poor possibilities, individuals can appreciate their life much more of what it really is.
Inner and outer qualities refer indeed to the individual and environmental features
representing the ground on which opportunities may growth.
Table 1.1. The four qualities of life
Quality of life Outer qualities Inner qualities
Life Chances Liveability of environment Life ability of the person
Life Results Utility of life Satisfaction with life
As shown in Table 1.1 the cross-products of these two these dichotomies determines four qualities of life:
1) liveability of the environment, 2) life-ability of the individual, 3) external utility of life and 4) inner appreciation of life.
This fourfold matrix constitutes the umbrella embedding all possible definitions of quality of life, it encompass both the objective and the subjective dimension of quality of life and relates them to the “external” and “internal” possibilities giving rise to the four qualities of life.
Liveability of the environment generally represents the qualities of the environment
that are relevant for meeting human needs. It delineates the level of “possibilities” given by the “external” dimension and thus representing a sort of pre-condition in which good life could or couldn't be developed depending on individual's ability. Liveability refers to something that is independent from individual wishes but which could be fundamental in determining the possibilities to realize individual needs and wishes. It denotes the meaning of good living condition both denoting objective material condition of the environment but also higher-level concepts referred to a general habitability of the environment.
Trying to associate the concept of liveability with specific definition or measure the term could be conceptualized just by using the point of view of a particular
defined as welfare and measured by social security, economical development, etc., sociologists may decline liveability in terms of social equality, close social networks or conversely as deprivation, social exclusion, etc. and so on for all the other disciplines.
Life ability of the person is produced by the inner attributes of the individual and the
external chances. It refers to the degree to which the individual is able to cope to objective condition given by the environment or the society. It is not the adaptation to external conditions - that is essentially a passive acceptation - but rather the ability to deal with life experience and ability is intended both in term of physical ability (inability), that is health (disease), and in terms of mental and psychological potential, that is mainly referred to the personal skill and strength of making the best possible and develop ability to enjoy life.
The so-called utility of life refers to the concept of giving a meaning to life that became useful to the society. It represents the external utility of life; independently of the inner value individuals are able to attribute to their life. In fact, even without being aware of this, an individual may give relevant contribution to the society, an inventor could contribute to the development of the society producing some material or objective effect that is highly valued from both in present and in the forthcoming society, utility to the society could also be expressed in terms of moral value given by a particular example of “virtuous living”. Utility is also given by a familiar or a caregiver who takes care of a person, by mother or father to her/his son, etc..
The last quality, satisfaction with life is the dimension most frequently associated with the general concept of quality of life rather than being considered just one of its concepts. Life satisfaction is the “subjective well-being”, more in general “happiness”. Life satisfaction refers to the inner valuation of life, life appreciation. It encompass the affective and cognitive appraisal of life experience, and it is determined by objective and subjective conditions that individuals valued per-se or by comparing his/her situation with the one of other individuals in the society. Humans typically judge their life comparing their actual condition with what they expect. They compare their material condition that is income, occupation, private life, etc. by referring to the condition of other known individuals but they also
compare intangible aspect of the life by affective feelings. From this comparison of the whole-life it derives satisfaction or dissatisfaction with life.
The one proposed represents just one of the schematization proposed for quality of life. The importance of such a kind of scheme rely on the fact that this analytic construction can be used to place and exploit the four quadrants pertaining the main life qualities to define the specific concepts and dimensions relating to them in order to guide a comprehensive measurement of quality of life.
In fact, as will be discussed in the next paragraph the identification of relevant dimension pertaining to quality of life is one of the primary steps for the development of appropriate instruments for quality of life assessment.
1.3 Health Related Quality of Life
In public health, medicine and health economy quality of life is frequently used as a synonymous of health related quality of life (HRQoL).
To be rigorous health related quality of life represents just one of the quality of life concepts and although ranging from aspects related to the pure physical health to mental health, passing also from the social aspect of human life, its definition, even broadened over the last decades, is concerned with all the dimensions of life that interfere with health.
Health has been implicitly embedded in the concept of quality of life from its first conceptualizations. This is the case of Humerus viewpoints cited in the previous section, his heroes, despite of being able to cope with life experiences, were always
healthy and vigorous and being affected by whatever form of illness or weakness
meant failure. Achilles is just one of the more famous example, although honest and brave he died just because he was victim of his interior frailty and of the only weakness of his body, his foot. The importance of health was also recognized by Aristotle's theory of happiness that identified illness as a source of detrimental effect for the individual well-being.
health policy. Particularly, the end of Second World War constitutes the change point from which it is dated the enlargement of the concept of health and thus the origin of the notion of health related quality of life.
The events characterizing the Nazi-Fascism period, the Jews prosecution, the holocaust and the complete “demolition” of human rights following the Arian theory, then called the community and the whole academic world to rethink about individuals, their rights and needs. In this context of restoring the value of health and human life born also the need for a more comprehensive definition of health. As a result of this change of mind the World Health Organization (WHO) elaborated in 1948 a new definition of health, that is no more the sole absence of disease or infirmity, but also “a state of complete physical, mental and social well-being”. Following this definition it clearly appears that according the WHO's point of view the measurement of health and effects of health care necessary imply the evaluation of quality of life.
A first attempt to go beyond the mere physiologic outcome evaluation was done by Karnofsky (Karnofsky DA et al. 1947.) with the development of the Karnosfky Performance Scale for cancer therapy evaluation, an 11-level scale describing patients’ condition with respect to physical independence and decline.
Despite this exception, it has took some decades before clinicians and scientists began to believe that the sole evaluation of the objective clinical condition couldn't give the whole assessment of outcome but also patient's perspective needs to be included to obtain a full assessment.
In fact the “paradox of health” teaches that better health status according to objective traditional indicators doesn't necessary imply improved well-being or satisfaction for health gain. Several studies exist now demonstrating the usefulness and validity of quality of life assessment in clinical settings; moreover self-rated global health has recently been proved to be a more powerful predictor of mortality than traditional clinical measures such as diagnostic criteria or laboratory measurements.
Individual perception of health related quality of life is not only related to the satisfaction or effects of an intervention but also to the perceived risk of certain conditions so that its assessment have demonstrated ability also in the evaluation of disease burden, preventable disease, injury and disability.
From the point of view of policy makers, the assessment of health related quality of life could outline the need for intervention in specific subgroups in relation to specific risk perception and guide resource allocation based on unmet needs.
The centrality of quality of life in health over recent years that has characterized most of the modern societies has thus been testified also at institutional level by the constitution of the World Health Organization Quality of Life (WHOQOL) Group at the end of the twenty century and by the creation of the International Society of Quality of Life (ISQOL) Research in 1994.
The well-recognized interest of politicians and scientist on health related quality of life has represented the transition towards a holistic view of the individuals that has produced also a shift of the objective of health and health care. Rather than being focused on the mere treatment of disease to restore physical and physiological functioning, health and health care have indeed been oriented to a broader restoration of human subjective well-being and health perception.
Moreover in the last centuries the elevation of life expectancy has drew the attention on the quality of added years of life and thus on the issue of the trade-off between quantity and quality of life.
Accordingly, health related quality of life has fast became a standard measure of outcomes in clinical practice thus evaluated in clinical trials and health economic analysis thus guiding also the proper evaluation of newly developed intervention and new health technology.
1.4 Areas and dimensions of Health Related Quality of Life
Despite being a slightly less broaden concept than overall quality of life, also referring to health related quality of life, the gap between theory development and its translation into practice has been the result of conceptual disagreement with consequent difficulties in finding appropriate measurement methods. The last obstacle have been overcame by placing and defining the relevant dimensions into a general scheme of the HRQoL qualities and thus developing standardized questionnaire with the well-established psychometric properties defined in the previous paragraph.
Developed and actually used instruments for HRQoL assessment are based on a core of main dimensions defined over years as a results of a general consensus over aspects answering the question “What's worth to HRQoL?”.
Following the recognition that health covers not only physiological aspects but also psychological, social and economic well being, six main dimensions have generally been identified as representative of HRQoL (Sullivan M. 1992):
• Physical complaints/well-being; • Psychological distress/well-being; • Functional status;
• Role functioning;
• Social functioning/well-being; • Health/quality of life perception.
These constitute the main domains that a measure of HRQoL would cover, each of these could then be exploited in several sub-dimensions as illustrated in Figure 3.1 that may differ among the various instruments.
Figure 1.1. Puzzle of Health related Quality of Life Components
Considering an ideal condition of good life that implies the achievement and fulfilment of needs and expectations in physical functioning, social relations, affective condition, education, working status, etc. thus offering an overall level of satisfaction meaning a good life, measures of health related quality of life try to evaluate if this ideal condition is reached and if not they try to quantify the distance from that condition.
Measures of quality of life have been proved relevant for clinicians and health planner in order to evaluate the overall burden of disease, to estimate and compare treatments effect, identifying special needs and improving quality of care. The assessment of health related quality of life has thus became quite common in medicine and clinical research and also clinicians now are very often interested in evaluating a certain treatment or intervention not only on the base of the objective clinical outcome but also considering patients' perspective.
The first one is referred to the underlying theory and the distinction is between
needs-based and preference-based measurements.
The other distinction relies on the purpose the instruments have been developed for and in this case it is possible to identify generic instruments, that are used and built to assess HRQoL in general without referring to a particular condition or disease, and
disease-specific instruments developed to focus on dimensions and problems that are
typically involved in a certain disease.
The distinction between generic and disease specific instruments will be further discussed in the next paragraph, while with respect to the peculiarity of needs and preference-based questionnaire, it will be sufficient to say that the first are based on the evaluation of how a specific disease or condition may interfere with the fulfilment of needs and mainly reflects Maslow's theory of well being (Maslow AH. 1943)
On the other hand preference based instruments are based on the utility theory and imply a valuation of specific health states ordering them according to a certain level of preference, these kind of measures are generally used to calculated adjusted
Chapter 2
Health Related Quality of Life in research
2.1 Measuring Quality of Life and Health Related Quality
of Life
To explicit and show their importance in the economic, social and health field quality of life need to be appropriately measured.
Three major goals could be associated with the measurement of quality of life: 1. discriminate;
2. predict; 3. evaluate.
Referring this goals to the health field what matter is to distinguish subjects with respect to different level of QoL in the population or in specific group of interest, to differentiate subjects based on their level of QoL with respect to a given gold standard embedding also a clinical meaning and finally to evaluate changes in QoL associated with the development of a certain disease or as a consequences of treatment or intervention.
Given the premise and the motivation for the need of measuring quality of life this chapter will present the main issues involved in the development of QoL instruments.
2.1.1 Instruments for Quality of Life assessment
Accordingly to the evolution of theories and the development of the different definitions of quality of life, it followed also the effort in finding instruments to measure it. Particularly in the first half of the nineteen-century when the interest around quality of life was moved by the need to evaluate how society's changes
life into a measurable quantity. The difficulty in finding a universal and general definition of quality of life was thus reflected in the development of a multitude of measures for its assessment, or rather it was just the effort of translating the definition of quality of life into measurable concepts that forced the different disciplines to abandon the labour for finding a general immeasurable definition to focus on a more specific one that will allow for an easier assessment.
Several measures of quality of life have been developed over years and most of them have also been progressively abandoned because of the evolution of theories and society so that they became outmoded. Moreover, as will be further discussed, most of the measures developed in the first attempts do not satisfied properties that are now required for instrument to be considered as a valid method for quality of life assessment.
To briefly describe the evolution and the complexity relying on the development of instruments for quality of life assessment we will quickly give some examples of the first questionnaires and indices developed with a rapid overview of their evolution into “complex” and valid instruments for assessment.
Despite some objective indices derived from indirect measures most of the old and quite all the currently used instruments for quality of life assessment relies on questionnaires, interviewer administered or self-compiled.
Witnesses of the first efforts to measure quality of life are dated to the beginning of the twenty-century and are attributed to American sociologists. In fact in 1922, following the interest in investigating socio-economic conditions of American families, Chapin (Chapin FS. 1922) developed a scale based upon a checklist item of objective evaluation in a house to be used to rate the socio-economic status of families.
In Chapin scale points were given based on the presence of absence in the house of items that could be considered a proxy of the family situation and these were:
• large rug (6 points),
• electric (12 points) or kerosene (-3 points) light, • sewing machine (2 points),
• telephone (24 points), • alarm clock (-5 points).
Further points were then added or subtracted based on the interviewers opinion on the general condition of the house.
This is just one of the first example of questionnaire developed for quality of life assessment. Several other measurements were settled in the USA in the subsequent years with the aim of evaluating the level of living of social family (McKain WC. 1939; Cottam HR. 1941), both relying on questionnaires and “administrative” indices. Further instruments were also developed in the sociological domain both including subjective indicators (Campbell AC et al. 1976) and others domains such as health (Gerson EM. 1976).
The use of gross domestic product (GDP) or gross national product (GNP) as relevant measures of well being constituted a further attempt to measure quality of life but in the economic field. In the same domains other relevant efforts were done in order to develop alternative measures such as the one proposed by Osberg and Sharpe (Osberg L (2001); Osberg L et al. 1998). The Osberg-Sharpe Index of Economics Well-Being was developed including the measure of consumption, allowances for wealth accumulation and inequality, economic insecurity comprising the risk of unemployment, illness, single parent poverty and old age. It had represented one of the first efforts made to develop a multidimensional index including several domains, although all strongly related to an economic perspective of quality of life. In the same direction was the work made by the economist Oswald Andrew and Bruno Frey, a scholar in economic psychology. They focused their research on measure of subjective well-being thus introducing a subjective valuation of the dimension concerning well-being (Frey BS et al. 2002).
Similarly to the examples given in the field of economy, generally the evolution of measures related to quality of life in all the disciplines involved in - with the exception of psychology - was characterized by a progressive increasing level of complexity due to the effort of making the measurement of the different dimensions as general as possible and also by the introduction of a subjective evaluation thus valuing the “inner” dimension of quality of life.
Only psychology had quite a different story because it is naturally oriented to the valuation of the subjective dimension of quality of life rather than on the objective
one so that it was just this discipline that gave the input to the different fields to consider an individual self-evaluation of quality of life.
Since health is the major field of interest of this work and will occupy the discussion in the next paragraph only a brief trace of the development of health related quality of life measure will be given in this paragraph.
It will be sufficient to say that also in medicine the evaluation of quality of life was initially based on clinicians’ assessments rather than on patients’ perception, using objective disease evaluation as well as death as the only indicator of quality of life. This method has thus been recognized to be limited and unable to detect individuals’ perception of health so that it has been integrated with subjective health perception.
2.2 The process of developing Quality of Life instruments
While the few examples given above about indicators of quality of life are based on the identification of simple measurable characteristics that may represent quality of life dimensions, the approach used nowadays to develop valid indicators follows a structured process involving the work and expertise of scientists in the specific field the indicator will refer to, statisticians and psychometricians.
Particularly, quality of life assessment is now generally based on a structured evaluation made by self-administered or interviewer based questionnaires and the process of development of these instruments encompasses some necessary and logically connected steps.
When the aim is to measure a particular aspect of life, as was in the example of the Chapin indicator that focused on the measurement of the economic situation of US families, it is just necessary to choose some elements that could be measured and used as indicator of the phenomenon we are interested in. Even though, also when focusing on just one area or aspect, the process of developing proper indicator will be not so trivial, things became extremely complex when dealing with multiple areas. For such a reason as the concept of quality of live evolved, even in the context of a specific discipline, to account for a broad definition - for example just encompassing both the subjective perception rather than the objective material condition - as the
The development of instruments for quality of life assessment has thus been characterized by the intervention of complex statistical and psychometric procedures in addition to the work of experts in the specific field.
Such a process became necessary for the development of instruments such as the ones currently used that allow for the assessment of the multitude of aspects involved in quality of life by using easy administrable questionnaire consisting in few clear questions (items) that could be answered even without the presence of an expert interviewer.
Particularly, a valid measure of quality of life not only need to assess all the domains involved into its definition but, to be useful and valid for research purpose, all these domains needs to be evaluated multidimensionally and synthesized so that they have to satisfy conceptual and psychometric properties such as content validity, reliability and inter-test correlation.
Defining an instrument for quality of life assessment means determining the specific dimensions of quality of life being of interest and then trying to find a measure for each of them. Thus frequently a measure of quality of life could result in a single qualitative or quantitative value, or rather it could also be possible to have different “sub-measures” coming from the different dimensions involved.
Even if unidimensional measure has been defined, typically most of the instruments that have been developed over years, and particularly most of those actually used, are multidimensional so that, even when referring to a particular filed, quality of life is generally measured by using multiple dimensions.
Typically each single dimension is scored thus obtaining a “profile score” and then all these score as summed up to obtain an “overall quality of life score”.
The steps involved in the development of such kind of instruments could be briefly summarized as an analytic process described as follows:
• definition of the conceptual model, • identification of areas of interest,
• use of statistical procedure to derive latent variables, • construction of indicators,
• questionnaire validation.
The definition of a conceptual model consists in defining and identifying the theoretical framework that will clearly delimit the field of interest. This phase involves mainly an expertise of the specific field in which the model will be applied, sociologists if we aim at defining an instrument for quality of life assessment to be used in sociology, economists for an economic evaluation of quality of life, clinicians for the health field and so on.
The exploitation of a conceptual model is necessary to confine and guide the identification of the specific areas of interest in which then measurable elements will be chosen as representative of the concept that the area represents.
A conceptual model is thus the envelope in which the different dimensions - aspects (represented by areas) - of quality of life should be further identified.
In the phase of identification of the conceptual model there is also the specification of the target population the instrument will be developed for.
Once areas have been defined it is necessary to identify variables that could be used to represent them. This step involves the use of statistical procedures since both directly and indirectly observable variable (latent variables) should be used to represent a certain area.
Variables should be selected in order to capture the whole concepts we will represent and are also required to satisfy some constrain in order to assure some properties that will favour the development of an instrument satisfying psychometric properties. Variables selected need then to be translated into appropriate item. Different methods have been proposed and used for the selection of relevant items to be included into a questionnaire.
Particularly item choice could be based on:
• interview of subjects from the target population; • focus-group;
• literature review including the revision of previously validated questionnaire and
There is not a reference method to be used for item selection rather the choice mainly depends on the framework of interest and on practical issues anyway – when compared - the diverse methods have shown often superimposable results.
Once items have been selected it is necessary to define the scales on which they need to be measured. In this case the choice is mainly between the “yes”/”no”, the visual analogic (VAS) and the Likert scale. While the first scale has the advantage to be extremely easy and practice but it may fail to proper capture the true feeling of subjects, the exhaustiveness of the VAS scale has the disadvantage to be not very easy understandable so that the Likert scale is a good compromise and for such a reason is frequently used.
In the phase of questionnaire development particular attention is given to the proper use of words with also a critical assessment of eventual problematic questions.
Once the questionnaire has been developed a pre-test assessment is recommended to check is validity and explore the reaction of patients for eventual revision.
Pre-test assessment is usually performed on a sample of the target population and may require more than assessment with a consequent iterative process performing at each time a revision of the developed questionnaire.
The latter step in the process of questionnaire development is the validation, that is the ultimate check of the questionnaire that allow for the use of the questionnaire being confident that the instrument is able to measure the concepts it has been developed satisfying standard psychometric properties.
2.3 Psychometric requirement of a Quality of Life instrument
As mentioned in the previous paragraph instruments for quality of life measurement are required to have good psychometric properties to be considered as valid measurements useful for research pour pose. These properties are:
• validity, • reliability, • responsiveness.
There are many types of validity; some of which can be judged only subjectively and also for such a reason they are often referred as low-level form of validity, this is the case of face and content validity. Face validity is the extent to which an instrument appears to measure what it is intended to measure. On the other hand content validity is the degree to which a test includes all the items necessary to represent the concept being measured.
Criterion and construct validity are therefore considered as higher forms of validity
being objectively examined. Criterion validity is the most straightforward type of validity and it refers to the ability of the instruments to agree with the concept it aims to measure. Construct validity reflects the capability of a test to measure the underlying concept of interest to researcher.
Reliability is the degree to which an instrument can produce consistent results, that is
to produce similar results when no changes have occurred, and to notice change when they actually happened. Reliability is generally referred to a particular population the instrument has been developed for and also different reliability measures exist.
Particularly test-retest reliability is typically assessed for self-reported instruments and measured by administering the instruments to the same subjects on several occasion in which it is assumed that no changes have occurred. Test-retest reliability often depends to the way answers are formulated, the words used, so that if they are expressed in a non-ambiguously way they will be interpreted in the same manner by the responder even in different occasions.
This type of reliability is of particular interest when instruments developed and validated in a country are translated into different languages to be used into different countries.
Internal consistency is another type of reliability and it is referred to the extent to
which items constituting an instrument represent the same underlying concept. This kind of reliability is useful for instruments measuring just one concept while it is not required for those instruments aimed at measuring different concepts, that is for example the case of quality of life that, as discussed before, even in the context of a single discipline, typically involve several concepts.
Finally responsiveness is referred to the ability of an instrument to accurately detect change when it has occurred and could be distinguished into internal and external
responsiveness. Internal responsiveness is defined as the ability of a measure to
change during a pre-specified time frame while external responsiveness reflects the extent to which changes in a measure relate to changes in other measures.
Reliability is a critical component of responsiveness. Measures with poor reliability will have difficulty detecting real change because the noise introduced by measurement error will obscure any real change that has occurred, but the same will happen for measure with poor content validity.
For a measure to be responsive, it must be reliable and include multiple items dealing with aspects of the construct that are likely to change, and the scoring of the items must allow for improvement.
Chapter 3
Generic and disease-specific health related
quality of life instruments
3.1 Generic Health Related Quality of Life Instruments
A lot questionnaires have been developed to be used in different situations in order to assess the degree to which physical and psychological conditions are perceived by individuals and how they impact on their life in general, comprising the social and environmental dimension as well as usual activities.
Because of this overall purpose, generic instruments assess the main domains of health coherently to what outlined in the previous paragraph even if among the different generic instruments there is some degree of difference both in relation to the core domains considered and consequently in the eventual sub-domains covered. The main advantages of generic instruments are that they allow for comparisons across different populations or subgroups and that they could also be used to evaluate HRQoL according to different disease. As a consequence their use is widespread in research.
In the next sections some of the generic instruments now available will be presented. Due to the large amount of instruments developed during the last decades we will focus only on those instruments that are most used in current practice in adults population.
3.1.1 Valuing Health Related Quality of Life
The increasing interest in HRQoL in the context of public health and the consequent use for overall evaluation and policy programming has led to the widespread use of HRQoL measure in economic evaluation with the consequent need for the identification of appropriate quantity to be used in this context, thus
giving rise to utility measure. As explained before utility measurement for HRQoL assessment are preference based instruments that are characterized by the possibility to express subjects' preference with respect to a particular outcome or condition by just using a single number unequivocally meaningful and comparable across different diseases and conditions but also among different populations and countries. The development of such kind of instruments derives from a long debate between economists and other professionals such as psychometricians.
In fact the assessment of HRQoL using measure of health as determined by "need-based" instruments do not provide useful indication of efficacy to be used in the economic evaluation. Particularly need-based instruments typically generated different profile scores describing each a particular aspect of health related quality of life and a summary score giving an overall evaluation.
Although giving a general indication about the state of the subjects the summary score derived from need-based measure is not so useful in understanding particular aspect of HRQoL that may be of relevant interest for example when evaluating a treatment or intervention. Let say that referring to a particular instruments the same total score may indicate for example a relevant problem in just one profile score or rather little impairment in more than one profile score, what is better?
It may depend on the degree of impairment but also on the area in which impairment is detected. Also in different situation or referring to a different intervention it may be more relevant a change in one particular area rather than in another one.
All these evaluations became unfeasible when using a need-based derived summary score or the different profile scores.
When comparing situations, treatment or intervention health economists aim at establishing which situation or intervention is better with respect to another one or more both in terms of cost and effect. A useful example of the uninterpretativeness of need-based measure for health economic evaluation is given below referring to the exemplification illustrated in Brazier J. et al. 2007 (Brazier J et al. 2007) and reported in Table 3.1.
Let's suppose to be interested in comparing two treatment in terms of cost-effectiveness, that is, given a standard or reference treatment, we’d like to identify
