Measuring the Quality of Life Before and After Bilateral Lung Transplantation in Patients With Cystic Fibrosis

Measuring the Quality of Life Before and After Bilateral Lung Transplantation in Patients With Cystic Fibrosis

preliminary study Measuring the Quality of Life Before and After Bilateral Lung Transplantation in Patients With Cystic Fibrosis* Jan]. \'. Busschbach...

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preliminary study Measuring the Quality of Life Before and After Bilateral Lung Transplantation in Patients With Cystic Fibrosis* Jan]. \'. Busschbach, M.Sc.: Paul E. Horikx, M.D. ; jules M. M. uan den Bosch , M .D., F.C .C .P.; Aart Bmtcl de Ia Ri viere, :\ I.D .. F.C .C.P. ; and Frank T. de Charm , Ph .D.

Lung transplantation is an important topic today in healthcare policy because the technique is new and costly. One of the important issues in the evaluation of lung transplantation is quality of life. The quality of life after lung transplantation must be relatively high compared with other forms of medical care to legitimize the high costs of transplantation. Quantifying the quality of life after lung transplantation and other medical therapies is possible with general measurements of quality of life. In a pilot study of six patients with cystic fibrosis, the quality of life, both before and after lung transplantation, was

measured by the following five instruments: (I) standard gamble, (2) time trade-off, (3) the Karnofsky performance status, (4) the EuroQol visual analog scale, and (5) the Nottingham health profile. This pilot study demonstrates that the introduced methodology is feasible. The preliminary results suggest that the improvement in quality of life for patients with cystic fibrosis after bilateral lung transplantation is comparable to the improvement in quality of life after heart transplantation.

In the Netherlands. healthcare policy-makers have particular interest in lun~ transplantation hecause it is a new and expensive treatment . \\'hen eYaluating a new therapy. healthcare policy-makers can use information about the number of vears of postsurgical surYi\·al. the quality of life. th e costs, ethics. and the opinion of the ~eneral puhlie . 1 This im·estigation tri es to estimate the quality of life before and after bilateral lung transplantation in patients with cystic fibrosis . The first section of this article giYes an introduction to the measurement of quality of life . Special attention is given to the measun' nwnts which can compare the ~ain in quality of life over different therapies. In the second section. a pilot stud~· of six patients with cystic fibrosis who were studied bpfore and after bilateral lung transplantation is presented to test the feasibility of the introduced techniques of measurement. This seems appropriate because some of the measurements of quality of life involve questions about life and death that may cause stress in patients facing transplantation . The pilot study is also meant

as an illustration of how to compare the gain in quality of life among different treatments . Comparisons based on six patients can only give tentative conclusions. Ne,·ertheless. the results of the pilot study can serve as first estimates in the early phase of the development of lung transplantation.

*From tlu· C<·ntre li >r lll'alth Polin· and Law. Erasmus Uniwrsil\· i \lr. Bnssehhaeh and Dr. 1fe Charro ). Rotterdam. and :\1itonim llospital ( Drs. llorikx . van de n Bosch. and BrutPI de Ia Hi,·ii·n •l. the 1\ i<•nw<'gl' in. :\dlwrlands . Ht'J>ri>lf rt'tjlll'sts: Dr. 1'011 dc11 Bosr h. St. A11toni11s Zit•kcnllllis . K.twkockslllflll I ..'J.J.].) C.\1 ,'Vit•tt rccgrill. till' !Vt·tlwrlmuls

(Chest 1994; 10.5: 911-17)

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Disease-Specific vs General Measu remcnts

Two different approach e s to evaluate the quality of life before and after lung transplantation are ( 1) disease-specific measurements and (2) general measurements.1 Physicians are most familiar with the disease-specific measurements . In the case of lung diseases , examples of disease-specific measurements are walking speed. the use of ox~·gen cylinders . and lung volume . Disease-specific measurements are very sensitive to small changes in quality of life . For this reason, the disease-specific measurements are important tools for deciding the best therapy for a specific disease. A disadvantage of disease-specific measurement is that they do not allow for comparisons among different diseases. Such comparisons can he important because they can help to formulate health policy. Therefore. general measurements of quality of life have been developed . Rather strai~htforward general measurements are the numCHEST I 105 I 3 I MARCH. 1994

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Table 1 -Different Forma of Meaaurement. of Quality of Life

Quality of life

Disease-specific measurement -Walking speed - Lung volume Objective general measurements - Lost work days - Days in hospital General measurement

Profiles - Nottingham health profile - Sickness impact profile Subjective general measurement Generic measurements - Quality of well-being -Time trade-off - Standard gamble - Visual analog scale

ber of days in the hospital, lost work days, mobility, etc. These measurements have to be supplemented by information about the subjective experience of the patient. Therefore, general-measurement instruments have been developed to measure the perception of quality of life by the patient. There are two groups of general measurements: (1) profiles and (2) generic unidimensional measurements (Table 1).

General Measurements of Quality of Life Profiles: The profiles distinguish different dimensions in the quality of life; for instance, the Nottingham health profile3 evaluates six dimensions: energy, pain, emotional reaction, sleep, social isolation, and physical mobility. This profile was used by O'Brien et al 4 in 1988 to assess the quality of life after a combined heart-lung transplantation. The questionnaire consists of two parts. Part 1 measures the subject!ve health status by asking for yes/no responses to a set of 38 simple statements relating to the six dimensions mentioned previously. Possible scores for each dimension range from 0 to 100. Part 2 contains seven statements referring to the consequences of health problems for occupations (paid employment, ability to perform tasks around the house, personal relationships, sex life, social life, hobbies, and holidays). The respondents answer "yes" if their present state of health is causing problems in any of these areas of life. The results are presented simply as a sum or percentage of the affirmative responses. 4 Generic Unidimensional Measurement: Profiles are consistent with the idea that quality of life is a multidimensional phenomenon; however, difficulties arise when one wants to compare the results of lung transplantation with other health care programs; for instance, it is hard to tell whether sleeping problems have a greater or lesser impact on the overall quality of life than difficulties with mobility. 912

Because of this, scientists have put a great deal of effort into developing a generic unidimensional scale for quality of life. Broadly speaking, a generic scale has a range from zero for death to one for perfect health. Often, for matters of convenience, the scale is transformed to a scale of 0 to 100. The values on the scale reflect utilities, and special interview techniques have been developed to measure these values. 1 A disadvantage of the expression of quality of life into one dimension is the reduction of information; however, reductions of complex phenomena into one scale have been proven to give acceptable solutions for many difficult problems of measurement in social science; for instance, cognitive function can be expressed as an intelligence quotient (IQ) and the prosperity of a country is measured by its gross national product. Pioneer work in the field of measuring generic quality of life in patients with cystic fibrosis has been done by Orenstein and Kaplan. 5 They worked out general principles 2·5 and applications. 6 ·7 For the applications, these investigators introduced the quality of well-being scale; however, the quality of wellbeing scale is only one of many possible alternatives. The different measurements of quality of life accentuate different aspects of the quality of life and may have specific advantages and disadvantages. Therefore, if the measurement is restricted to the quality of well-being scale, important information can be lost. In the following paragraphs, other frequently used generic measurements will be introduced, such as the Karnofsky performance status, the standard gamble, the time trade-off, and the EuroQol visual analog scale. The first measurement introduced here is the Karnofsky performance status. ~-9 The Karnofsky performance status is a list of 11 states of health. Each state of health has been assigned an index ranging from 0 for death to 100 for the health state without problems. The Karnofsky performance status was

Quality of Life Before and After Bilaeral Lung Transplantation in CF Patients (van Busschbach at a/)

Table 2- Standard Gamble

A choice between:

Operation with a chance (p ) of dying and a chance {1 -p ) of total cure or Living in the chronic health state until natural death

not originally designed as a utility measurement; however, its outcome seems to correlate on a high level with more sophisticated measurements like the quality of well-being scale . ~ The Karnofsky performance status is an old and well-known instrument in clinical practice. In its original form, the scale was written in the third person and was administered by the physician . In some studies, the scale was translated into the first person so that the patients could fill in the questionnaire themselves .10 Another utility measurement is the visual analog scale . An example of a visual analog scale is the one developed by the EuroQol group .11 The EuroQol visual analog scale is a calibrated line, sometimes called a "thermometer," numbered from 0 to 100. The bottom of the line is labeled the worse imaginable health state, and the top of the line is labeled the best imaginable health state. The patients are asked to mark the point on the line that best represents their present state of health. The third measurement introduced here is the standard gamble. The standard gamble is based directly on the fundamental axioms of utility theory. 1 The patients are asked to choose between living with the disease or having a risky operation that could result in either a complete cure or immediate death (Table 2) . The main principle of the standard gamble is that patients are willing to accept a higher risk of death (as a consequence of a hazardous therapy) if their health state is worse than if their health is relatively good. The amount of risk that patients are willing to take reveals information about the quality of life of the health state .

The last generic measurement introduced here is the time trade-off. Time trade-off is a technique derived from the standard gamble that avoids the difficult risk factor . Patients are asked to indicate the maximum number of years they are willing to give up in order to avoid a poor state of health; fornstance, patients are asked, ".. . if there was a medicine that could change your present health state to a normal state, but it would decrease your life by 10 years, would you take that medicine .. . ?" Patients in a very poor health state tend to accept a substantial decrease in their life span. The number of years of life that patients are willing to give up gives an indication of the quality of life in that particular health state.

Quality-Adjusted Life Years Unidimensional indices of the quality of life , as described previously, can be used to construct quality-adjusted life years (QALYs) . The years of life of a patient are multiplied by the health index (utility) involved; for instance, if a patient with cystic fibrosis lives for 8 years after transplantation with a health utility of 0.8, then the outcome of surgery is 8 x 0.8 = 6.4 QALYs. This idea has been described by Orenstein et aJS for the case of cystic fibrosis and lung transplantation, although these investigators use the term, "well-year," instead of the more current term, QALY. When the impact of a therapy is described in terms of QALYs, policy-makers have a powerful tool to compare the results of different healthcare programs. The two main effects of a therapy, survival and quality of life, are combined into one scale. Also, an estimation of the efficiency of the therapy can be made by calculating cost per QALY gained. In the literature, QALY analysis has been questioned;12. 14 however, besides the QALY analysis, there is still no generally accepted alternative to compare all effects and costs of different healthcare programs simultaneously. 1

Clinical Course Too early

Time

'

Toolate

FtGUIIE

1. Transplant window.

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Utility 1.0

Transplantation

0 FIGUHF. 2. Theoretical course of cystic fibrosis .

Applied to patients with cystic fibrosis, a QALY analysis could have the following shape. In the beginning, most patients are relatively well. With the aid of medical treatment, the patient can live a rather normal life. Then the patient's health progressively deteriorates. If no lung transplantation is performed, the patient will die within a few years. During this period of decreasing health, the decision for lung transplantation must be made. The exact timing depends on several different aspects of the condition of the patient. External factors also play a part, such as the expected waiting time before a donor organ is available. Because the interpretation of all of these factors is complex, the timing of surgery is not a point in time , but an interval, which is the so-called transplant window 15 (Fig 1). When the surgery is done too early, the risks of dying as a direct result of the transplantation may be too high compared to the possible life extension. When the transplantation is postponed, the condition of the patient may have declined too much for the operation. After successful surgery, health rapidly improves, followed by a stable period in which the patient is relatively well . This theoretical development of the disease is pictured in Figure 2. The area under the curve represents the number of QALYs (timex health utility). To determine the curve, the following three utilities are the most important: the utility of health before the transplant window, the utility of health during the transplant window, and the utility after recovery. THE PILOT STUDY

Methods A pilot study was set up in order to estimate the quality of life before and after bilateral lung transplantation in patients with cystic fibrosis . At the moment of measurement, eight patients with cystic fibrosis were participating in the lung transplantation program at the Antonius Hospital in Nieuwegein , the Netherlands. Before the pilot study started, 2 patients had died after transplantation; I died 6 days after transplantation and the other

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Time 96 days after transplantation. These two patients were not included in the investigation. Three of the 6 patients who were alive at the time of the investigation had undergone lung transplantations 12, 14, and 16 months earlier. These 3 patients left the hospital at 27, 31, and 40 days after transplantation . The other three patients were on the waiting list. During the investigation , no lung transplantations were performed. Therefore, it was not possible to make a longitudinal study. As an alternative, retrospective data were colleeted. In order to get these retrospective data, patients were asked to imagine that they were still in a previous state, for instance, in the transplant window. The patients with transplants gave "retrospective information " about the time before and during the transplant window and "actual information " about the period after transplantation. Patients on the waiting list gave retrospective information about the time before the transplant window and actual information about the time during the transplant window. The results obtained with this methodology are not straightforward and should be used prudently. On the other hand, retrospective data may have some special qualities. Patients with a low quality of life and an expected short life span seem to have difficulties in making trade-offs between quality of life and their short life span in the standard gamble and time trade-off. In these imaginary questions , such patients are often not willing to shorten their life span.'" Therefore, actual information on pat ients in the transplant window might estimate the quality of life too high . In that case, retrospective data might he a reasonable alternative. Five of the 6 patients with cystic fibrosis were between 20 and 30 years old (mean, 25 ± 4 years [SD)). The sixth patient was exceptionally old (52 years). She was one of the patients on the waiting list. Four of the six patients were women . Five measurement instruments were used: the Nottingham health profile. the standard gamble, the time trade-off, the EuroQol visual analog scale, and the Karnofsky performance status. In general, the methods were executed as described in section I. A spedfil· detail of the execution of the standard gamble and the time trade-off was that natural death , with or without the disease, was set at 75 years, so with the standard gamble and the time trade-off. all health states were seen as if they were chronic. It was stressed that the imaginary situations suggested in the standard gamble and the time trade-off did not exist in reality. This was done because emotional stress was expeeted when the patients would be confronted with the standard gamble and the time trade-off. There was also the risk that false hope would be given, because the patients would possibly think that the imaginary situations were real. In order to handle this delicate

Quality of Life Before and After Bilaeral Lung Transplantation in CF Patients (van Busschbach at a/)

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~10

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fibrosis.

.,.,_

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3. Quality of life before. during, and after the transplant window in six patients with cystic

Lung Transplantation

situation. the patients went through a comprehensive informed consent procedure. Also, in order to minimize and control stress, the first author, who is a psychologist, interviewed the patie nts in their own homes.

Results The patients did not demonstrate high emotional stress while they answered the questions about life and death . Figure 3 presents the individual data of the six patients for the four different general generic measurements. The Y-axis represents the utility of the health states. Here, the utility index has a value of 100 for a good health state and zero for death . In general, the utility of the health states decreases when one has entered the transplant window. After transplantation, the utility increases to a level above the health state before the transplant window. It was surprising to find that the older Karnofsky scale gave almost the same results as the more sophisticated methods. Figure 4 shows the overall means for these data. This figure shows that different measurements do not give exactly the same results. Because one does not know which method gives the "real utility," the estimated utility is not a point, but rather an interval. The results of the Nottingham health profile, part 1, in Figure 5 suggest two major areas of dysfunction during the transplant window: energy and physical mobility. After surgery, the problems in these areas disappeared. Before and after the transplant window, no major dysfunctions are present. In fact, the problems reported in part 1 before and

no

Kamofsky Standard Gamble EuroQol VAS *before

a during +.,..,

Heart Transplantation 80

~60

s40 20 0 O'Brien ~----------------------------~ & Furguson Six Point VAS (Bonsel) Kamofsky (Bonsel)

e

during+ after

4. General measures of quality of life before, during, and after the transplant window. FI<:UHF.

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Heart Transplantation

Lung Transplantation ~

100

!I c ·a

100

~

80

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80

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8

15.

60

60

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Emotional ,. .c. Soci81 isolat. Physical mobil. Slnp Pain

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Energy

Emotional n1ac. Social isotat. Physical mobil. Steep Pain

Fua·nE -5 . :>lottingham health profile , part 1. before. during, and after the transplant window. Heart transplantation data are from Bonsel et al. "'

after the transplant window seemed to be below the values of a normal healthy population . These normal values are between 3 and 10 for the different dimensions. The low values found in this study are in accordance with the clinical impression that the patients with crstic fibrosis have a tendency to deny their problems for reasons of coping. Discussion

The patients showed no signs of distress when they answered the standard gamble and time tradeoff questions. This is an indication that these questions im·olving matters of life and death can be asked if a proper introduction is given. The standard gamble seems to produce the highest values for the health states . This is due to the fact that most patients are averse of risk. Patients are more willing to give up an amount of time than they are willing to take a comparable amount of risk. 1 ~- 1 s For the better health states, the EuroQol visual analog scale produces relatively low values. This is probably due to the fact that the utility of LO is marked as the best imaginable health state while the other measurements define LO as the absence of disease . In general , values on a visual analog scale tend to be lower than values measured with other means of assessment. 1 ~· 19 · 2 " In the field of measuring quality of life, there is no "gold standard." Therefore, it is not clear which of the four general measurements produce the "real utilities;" however, estimates based on this study would suggest that the utility of the quality of life in patients with cystic fibrosis before the transplant window is about 0.8. In the transplant window, the health utility drops to 0.4. After transplantation, the quality of life increases to 0.9. It is important to understand that these numbers are the first estimates and not firm statements, due to the low number of patients involved and the risk of missing 916

worst cases in this early state of the diffusion of the technique of lung tra1;splantation. It was clear that the disease and the transplantation put a heavy load on the lives of the patients and their families . Everyone involved showed impressive fighting spirit, but, as said before, clear coping mechanisms were also apparent. Both within the transplant window and after transplantation, patients seemed to overestimate their possibilities and quality of life at that present time. This is visible in Figure 3, where the highest values for the quality of life before transplantation belong to the patients on the waiting list. During the interview, coping mechanisms were noticed when the patients in the transplant window filled in the Karnofsky performance status. Those patients found it hard to admit that they were dependent on the support of others and that they were frequently in need of hospital care . These observations and the results from McNeil et aJl 6 suggest that the assessment of the quality of life in seriously ill patients is heavily influenced by coping mechanisms. The collection of retrospective data could be a possibility to control these coping mechanisms. For reasons of comparison, the results of different studies about quality of life before and after heart transplantation are presented in Figures 4 and 5. 10·2 1.22 When one compares the results of this pilot study with the results of the studies of heart transplantations, the resemblances are remarkable. The improvement in general quality of life is about the same and manifests itself in the same dimensions (the visual analog scale used in the study of heart transplantation also produced lower values) . The similarity is relevant for Dutch healthcare policymakers, because heart transplantation is now funded by public health and private insurance companies , while lung transplantation is only paid for under special conditions and restrictions set by the

Quality of Life Before and After Bilaeral Lung Transplantation in CF Patients (van Busschbach eta/)

government. If both lung and heart transplantations produce the same quality of life, then the quality of life is no longer an argument to justify a difference in funding.

Conclusion The results of this pilot study are very preliminary due to the small number of patients; however, an important conclusion is that in patients undergoing lung transplantation, it is feasible to measure quality of life with the standard gamble, the time tradeoff, and the EuroQol-visual analog scale. Patients do not experience high levels of stress when the interviewer chooses appropriate interview settings. The first results of this pilot study justify the hypothesis that the improvement in the quality of life after lung transplantation is similar to the improvement in the quality of life after heart transplantation. ACKNOWLEDGMENT: We thank Gouke J. Bonsel, M.D., for his constructive criticism and Ms. Gretchen Vroege-McGrath for her linguistic assistance.

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