Validating the EQ-5D with time trade off for the German population

Transcription

1 Eur J Health Econom : DOI /s z Published on line: 22. De cem ber 2004 Springer Medi zin Ver lag 2004 W. Grein er 1 C. Claes 1 J. J. V. Buss chbach 2 J.-M. Graf von der Schu len burg 1 1 Cen tre for Health Eco nomics and Health Sys tem Re search, Uni ver si ty of Hanover, Hanover, Ger many 2 Institute for Medical Psychology and Psychotherapy, Erasmus Medical Center, Rotterdam, The Netherlands Validating the EQ-5D with time trade off for the German population Introduction Research question Cost-ef fec tive ness anal y ses in health care of ten use the Eu ro Qol EQ-5D to assess the out comes in terms of qual i ty-adjust ed life-years (QALYs). The val ues attached to the EQ-5D health states are usual ly those se lect ed in the Unit ed King dom by re searchers at the Uni ver si ty of York [7]. Al though the British study has been the largest and best doc u ment ed study of its kind, the use of British val ues abroad may not be jus ti fied if na tion al or cul tur al differences determine large differences in val ues [2]. Pre vi ous re search demon strates that val ues based on vi su al an a logue scales (VAS) do not dif fer sub stan tial ly be tween coun tries in west ern Eu rope [4]. Nev er theless, time trade-off (TTO) val ues ap pear less ro bust [1, 9, 12]. For this rea son there is a need for na tion al TTO val u a tion studies. This study at tempt ed to es ti mate German TTO val ues for the EQ-5D. Background Health care costs have in creased more rapid ly than the gross na tion al prod uct in almost all Western industrialized countries In re cent decades. While in mar ket sys tems the price is the cen tral in di ca tor for the scarci ty and the ap pre ci a tion of a good, mar ket sys tems reg u lar ly fail in 124 Eur J Health Econom health ser vices, for ex am ple, due to the special fea tures of the pro fi cient health care, ethical considerations, and urgency. Therefore, con sid er ing the fixed price and ne go tiation price systems, budgetings, managed care sys tems, among oth ers, are in clud ed to con trol health sys tems and to al lo cate (dis patch) health goods. The dif fer ent control sys tems (and com bi na tions of them) op er ate well on the whole, but fre quent dissat is fac tion is seen among the pa tients or oth er par tic i pants of the sys tem, and unwant ed ef fects re sult, such as in ra tioning. More of ten than not these sys tems have little con sid er a tion for the de sires and needs of the pa tients and the pop u la tion. This ex pe ri ence forces the health-polit i cal tar gets along side the cost sav ings in health ser vices to en sure an in crease in ef fi cien cy of the health sys tem to find or to justify decisions on allocation. The fun da men tal ques tions are in which areas and for what ther a pies in health care should the fi nan cial means be dis tributed? Thus, why must old and new ther a- pies and health programs continuously ensure a positive cost-effectiveness? While ther a py costs can still be suf fi cient ly expressed in mon e tary units, it is dif fi cult to evaluate the utility of therapies and to compare the utilities of different medical in ter ven tions. Health care can ex tend the pa tient s life (life years gained), im prove health-related quality of life, or decrease costs of fu ture health care. More over, it is re al ized that the per spec tive of the pop u- lation, with their characteristic as taxpayers and po ten tial pa tients, must also be taken into ac count when mak ing de ci sions about allocation. The population s perspective is ex pressed in the ap pre ci a tion of single health states, i.e., how good or how bad health states with dif fer ent re stric tions are judged. There is no gold stan dard for mea surement of qual i ty of life ef fects of med i cal benefits. Countless questionnaires, usually ill ness spe cif ic, have been de vel oped, with large ly dif fer ing ob jec tives. It is extremely difficult to evaluate the success or outcome of alternative therapies or to provide an ori en ta tion for de ci sion mak ing with illness-specific instruments, as only generic index instruments allow comparisons be tween health eco nom ic re sults in cost efficiency analyses of different studies or indications. Al though both tar get pa ram e ters health and health-re lat ed qual i ty of life are con tro ver sial con cepts, it is broad ly agreed that they con tain dif fer ent di mensions, for ex am ple, the emo tion al, so cial, physical, and psychosocial functioning of persons. Profile instruments such as the SF-36 and the Not ting ham Health pro files examine the health-related quality of life for each in di vid u al di men sion sep a rately. How ev er, a sin gle in dex which ex amines one out put for each pos si ble health state is necessary for cost-efficiency analyses. Otherwise, it is impossible to exam-

2 Abstract ine costs and utilities of alternative therapies or indications. Apart from the dif fi cul ty in quan ti fying such a com plex is sue as health-re lat ed qual i ty of life, a fur ther prob lem re sults from the fact that nu mer ous di men sions must be ag gre gat ed to a com mon scale in QALY anal y ses. In the pres ent study states are described using the terminology of the de scrip tive EQ-5D sys tem. The task is to find a pro ce dure which ag gre gates the population s appreciation of the EQ-5D health states in a pref er ence-based EQ-5D In dex. There are essentially two alternative methods: the bot tom-up ap proach and the topdown ap proach. In the for mer the re spondents are asked to eval u ate each re sponse lev el of the dif fer ent di men sions ce teris paribus (i.e., un der oth er wise iden ti cal con di tions), i.e., the lev els of the re maining di men sions are kept con stant. The topdown approach requires a valuation of health states as a whole from each re spondent in or der to gen er ate the in di vid u al response levels afterwards. Appreciation of health states can be de ter mined with the help of different valuation methods. The most com mon meth ods are the VAS, standard gam ble, and TTO. In the pres ent study val ues for the EQ-5D were de rived us ing the top-down VAS and TTO pro tocols as de vel oped by the MVH group at the York Uni ver si ty [7]. Method Sampling Be tween Oc to ber 1997 and March 1998, 18 trained students interviewed a representative sam ple of the Ger man pop u la tion in the north ern Ger man states of Low er Saxony and Bremen. The interviewers visited the re spon dents at home, as in the British study. The sam ple was se lect ed us ing a two-stage pro ce dure. First, a sam ple was randomly selected from the telephone directory. To represent urban and rural regions equal ly the se lec tion was based on postal zip code ar eas. Be cause the male name of a mixed house hold is pre ferred in the tele phone reg is ter, one-half of the per sons se lect ed were wom en to avoid a se lec tion bias. Those se lect ed for this sample were re quest ed in writ ing to par tic i- pate. Par tic i pants were of fered a cer tain cash re ward and could re spond us ing a reply card. In ter view dates were ar ranged by tele phone. If it was not pos si ble to es tablish a mu tu al ly ac cept able date for a meeting or af ter three failed at tempts to con tact the per son the in ter view was can celed. Of the 380 respondents who reacted positively on the writ ten in vi ta tion 339 could be interviewed. Subjective valuations of the quality of life have a high vari abil i ty. In that re spect it is help ful to ex clude ex treme val ues which are sub stan tial ly over or un der most oth er val ues in the anal y sis. The meth od used here was based on a box plot; ex treme scores in the box plot were re moved form the data. The ex treme val ues were char acter ized in the box plot by the dis tance of more than 1.5 of the draw ers away from the mid dle val ues. These ex treme val ues of both the VAS and TTO data were ex cluded from fur ther anal y sis. Note that this is a different procedure than that followed by the investigators in the United Kingdom, who elim i nat ed all re spons es of re spondents with no differentiation between respons es and large in con sis ten cies. Modeling A par tic u lar prob lem in val i da tion studies such as this is the im pos si bil i ty of obtaining direct empirical valuations for all (n=243) EQ-5D health states. Pi lot stud ies have shown that re spon dents are un able to eval u ate more than about 15 health states at one time. This num ber was con sid ered too low to ob tain a rep re sen ta tive se lection for interpolation of all 243 theoretically pos si ble EQ-5D health states. This consideration was based on experience with the mod el ing of VAS val ues us ing the 12 com mon core health states of the Eu ro- Qol group. Fur ther more, the se lec tion of the health states should cov er the complete span of the EQ-5D-health states and if pos si ble all ag gre ga tions of the di mensions or re sponse lev els [1]. This study select ed 36 health states, and each re spondent was asked to eval u ate a sam ple from these. These 36 states were se lect ed from the 42 val ued in the Unit ed King dom. The re duc tion in num ber from 42 to 36 was conducted in close consideration with the British investigators. Based on their experi ence with this ex trap o la tion, they felt Eur J Health Econom : DOI /s z Springer Medi zin Ver lag 2004 W. Grein er C. Claes J. J. V. Buss chbach J.-M. Graf von der Schu len burg Validating the EQ-5D with time trade off for the German population Abstract The aim of this sur vey study was to de rive the so ci etal val ues of the gen er al pub lic for the Eu ro Qol EQ-5D. Us ing the same pro to col as pre vi ous ly used in the Unit ed King dom, we com pared the Ger man val ues with the British. In face-to-face in ter views a sam ple of 339 in di vid u als in north ern Ger many valued 15 dif fer ent health states from a sam ple of 36 states. Val ues were de rived us ing the York MVH pro to col for time trade-off (TTO) and a visual analogue scale (VAS). Values for all 243 health states of the EQ-5D were estimated by a regression model. The VAS val ues re vealed close a re sem blance to the British VAS re sults. Ger man TTO val ues were higher than the British. This was especially the case for the worse health states. The results sug gest that the TTO val ues are more related to national variables than values derived by VAS. The use of the TTO val ues of this in ves ti ga tion makes it pos si ble to an tic i- pate these cul tur al dif fer ences in stud ies carried out in Ger many. Keywords Cost-effectiveness Utility measurement Quality-adjusted life-years Quality of life Population study Eur J Health Econom

3 that 42 health states may not be need ed to make valid interpolations. An obvious advan tage is that by re duc ing the num ber of states, the num ber of val u a tions (re sponses) per health states in creas es. This makes the av er age val ues per health state more reli able and makes it pos si ble to re duce the sam ple size of re spon dents. The ar gu ments were cod ed as fol lows: A vari able for each EQ-5D di men sion which il lus trates the mod i fi ca tion of response lev el 1 (no prob lems) to re sponse lev el 2 (some prob lems) or the mod i fi cation of re sponse lev el 2 (some prob lems) to re sponse lev el 3 (ex treme prob lems). Fur ther more we used a dum my vari able for each EQ-5D di men sion which rep resents the modification of response level 1 or 2 to re sponse lev el 3. Fi nal ly we in cluded a dum my vari able with the val ue 1 for health states with at least one di men sion with lev el 3 (ex treme prob lems), for ex ample, and This lat ter dum my variable is the fa mous N3 vari able.. Table 1 pro vides an overview of the vari ables in the mod el. Analysis To test the va lid i ty of the mod el we used the R 2 sta tis tic, which in di cates the suc cess of the mod el ing ex er cise but can not be inter pret ed in an ab so lute sense, as its size is a function not only of misspecification but also of the range of the health states [5]. Fur ther more, R 2 is an over all measure. This makes it dif fi cult to de ter mine whether the mis spec i fi ca tion is due to small generic misspecifications or to one or two large lo cal de vi a tions. For this reason an individual inspection of the specifica tion of the over all range of health states can be illuminating. The statistical significance of the coefficients indicates whether we have suc ceed ed in fit ting an ad e quate model. Interview protocol The interview followed the original MVH pro to col as close ly as pos si ble. Also, the visu al adds and in struc tions were copied precisely to allow comparison between the differ ent val u a tions stud ies. The in ter view comprises several sections. After the interview er in tro duced him self and de scribed 126 Eur J Health Econom briefly the back ground of the study the respon dents were first asked to give some information about their sociodemographic back ground and to an swer the five questions of the EQ-5D de scrip tive sys tem for their own health state. Af ter this in tro duc tion the in ter viewer pre sent ed the re spon dent with a sample of the se lect ed 36 cards and a card labeled death. Each re spon dent val ued between 13 and 15 health states per in ter view. On the cards are de scrip tions of health states ac cord ing to the EQ-5D sys tem. The re spon dent was asked to read these cards very care ful ly and rank them from good to worst health states. This rank ing rep re sents the val ues for a per son like themselves. The respondent was told to as sume that he or she would live in that health state would for 10 years, af ter which the sub ject would die. The next ex er cise for the re spon dent was to val ue the health states on a VAS: the EuroQol thermometer. The VAS was made twice as large (A3 for mat) as the one used in the Unit ed King dom (A4) to al low the re spon dent to place the cards next to the scale. Dur ing the VAS task the re spondent was al lowed to al ter the card se quence com pared to the rank ing ex er cise. At the end of this VAS task the re spon dents mark the val ue for their own cur rent health state on the VAS. In the last part of the in ter view the cards were evaluated unranked according to the TTO meth od. The same health states were used, ex cept for and death, which are an chor states in the TTO ex ercise. For this pur pose a dou ble-sid ed time board was used as a vi su al add. On the front and back side of the time board are two time axes, marked life A and life B. On the front of the time board the time axis of life A is the ref er ence health state (health state with out re stric tions). The cards that should be eval u at ed were pre sent ed as life B. While the time of life B is 10 years in ev ery case, the time of life A can be var ied be tween 0 and 10 years. Fol low ing this the re spon dent had to imag ine that he was cur rent ly in the health state de scribed on the card. As in the rank ing and VAS task, the re spon dent was told to imag ine that the health state would stop af ter 10 years, and that he or she would die. A con trol ques tion re quests the ver i fica tion that the re spon dent prefers the alter na tive to live 10 years in the health state with out re stric tions (life A) than in the health state with re stric tions (life B). If the respondent decided for life B instead, the in ter view er de scribed the pro ce dure once more. If the re spon dent still could not mas ter the task, the in ter view was end ed. Subsequently the interviewer asked whether the re spon dent would pre fer to die im me di ate ly rather than to sur vive in life B. The interviewer visualized this question by shift ing the time board nee dle of life A to 0 years. If the re spon dent pre ferred life B, the life time in life A was set to 5 years with the ques tion whether the re spon dent would pre fer 5 years in the health state with out re stric tions (life A) in stead of living 10 years in the health state as signed in life B. If the re spon dent de cid ed for life A, the period was subsequently shortened in year ly steps (suc ces sive ly 4, 3... years) until the per son de cid ed for life B. In the reverse case the pe ri od of life A was ex tended in year ly steps (6, 7... years) un til the respon dent pre ferred life A in stead of life B. As soon as this change took place or the respondent claimed to be indifferent between the val ue of the two health states, the in ter view er not ed the re sults and proceeded by introducing the next card. A spe cial sit u a tion oc curred when ever no change had been achieved at the val ue 9 years. In this case the in ter view er asked the re spon dent whether he or she was will ing at all to sac ri fice a cer tain peri od (weeks or months) in or der to avoid life B. If the re spon dent start ed the tradeoff pro ce dure by stat ing that 0 life years in life A were pre ferred over 10 years in life B, the interviewer proceeded with the reverse side of the time board. This side of the board was spe cial ly de signed to val ue health states con sid ered worse than death. Life B now represented immediate death. Life A was now di vid ed into two parts: the respondent should imagine living t years in the health state as de scribed on the card, fol lowed by 10 t years in the health state with out any health prob lems (11111). This situation is comparable to that of patients who are on a wait ing list for a cer tain ther a- py and ex pect to re gain com plete health after this ther a py. The start ing point for this part of the interview was a situation with

4 a 5-year wait ing pe ri od in the health state with re stric tions and 5-year life time without restrictions. If the respondent decided for life B (im me di ate death), the wait ing pe ri od was re duced to the point at which the re spon dent de cid ed for life A or con sidered the al ter na tive equal. In the re verse case the waiting period was extended. Calculation of the TTO value To cal cu late the TTO val ues the pro ce dure of the MVH pro to col was used. The first part of. Table 1 de scribes how the val u a tions of health states be tween good health and death are standardized to a value scale between 0 and 1. Val u a tions of health states worse than immediate death are standardized between 0 and 1. The jus ti fi ca tion for the bound ary of 1 is pro vid ed else where [7, 10, 11]. To facilitate comparison with the British data a small cor rec tion was made for the wider steps in the trade-off. In the orig i nal MVH pro to col the steps were re fined to 0.5 year; in the present investigation they were 1 year wide. The ad di tion or sub traction 0.5 year of the trade-off seemed ap propri ate. For ex am ple, if a change from life B to life A hap pened at 7 years, it was assumed that the re spon dent would al ready have de cid ed for a change with a re maining life time of 6.5 years. If the re spon dent was in dif fer ent be tween lives A and B or t was spec i fied in weeks, the 0.5-year cor rection of t was omit ted (. Table 2). Results Respondents Table 1 Model variables and values A MO SC UA PD AD M2 S2 U2 P2 A2 N3 Table 2 In ter cept 1, if mo bil i ty is on lev el 2 (some prob lems) 2, if mo bil i ty is on lev el 3 (ex treme prob lems) 1, if self care is on lev el 2 (some prob lems) 2, if self care is on lev el 3 (ex treme prob lems) 1, if usu al ac tiv i ties is on lev el 2 (some prob lems) 2, if usu al ac tiv i ties is on lev el 3 (ex treme prob lems) 1, if pain/dis com fort is on lev el 2 (some prob lems) 2, if pain/dis com fort is on lev el 3 (ex treme prob lems) 1, if anx i ety/de pres sion is on lev el 2 (some prob lems) 2, if anx i ety/de pres sion is on lev el 3 (ex treme prob lems) 1, if mo bil i ty is on lev el 3 (ex treme prob lems) 1, if self care is on lev el 3 (ex treme prob lems) 1, if usu al ac tiv i ties is on lev el 3 (ex treme prob lems) 1, if pain/dis com fort is on lev el 3 (ex treme prob lems) 1, if anx i ety/de pres sion is on lev el 3 (ex treme prob lems) 1, if any lev el is on 3 (ex treme prob lems) Conversion of raw TTO values Val ues greater than death: t=the num ber of health years in the-trade off Val ues t>5 TTO val ue=(t 0.5)/10 Val ues t<5 TTO val ue=(t+0.5)/10 If t was in di cat ed with n weeks TTO val ue=[9+(t/52)]/10 Val ues be low death: t=the num ber of dis abled years in the trade-off Val ues 0<t<5 Val ues 5<t<10 TTO val ue=[(t+0.5)/10] 1 TTO val ue=[(t 0.5)/10] 1 Exceptions Indifferences between life A and B If respondents were indifferent, the 0.5 cor rec tion was not nec es sary. Five of the 339 in ter views had to be terminated prematurely because the respondents could not mas ter the ex er cise. Vari ous in flu ences dis tort ed the struc ture of the sam ple, which had orig i nal ly been randomly selected. The return of the re ply cards showed ad dress es of wom en to be underrepresented. A possible explana tion is that wom en were re luc tant to conducting an interview at home. Anticipat ing on this re luc tance, al ter na tive neutral in ter view venues were of fered, but this op por tu ni ty was not used at all. In ad di tion, the age groups of em ployed persons were underrepresented. Due to employment these persons were restricted in find ing time to con duct the in terview, al though the stu dent in ter view ers did of fer dates on the week end if nec essary. The in ter view last ed 43 min on average. Older respondents generally needed some what more in ter view time than younger (P=0.01, Mann-Whit ney U test). The in ter view du ra tion also de pend ed on the in di vid u al in ter view er (P=0.01, Kruskal-Wal lis H test). Data qual i ty The pro por tion of ex treme val ues that were elim i nat ed from anal y sis amount ed to about 1% of VAS val ues, with a band- Eur J Health Econom

5 Table 3 Di rect TTO and VAS val u a tions of se lect ed EQ-5D health states VAS 1997 Mean ±SD VAS 1994 Germany width from 0% to 6%. The TTO val ues showed more ex treme val ues: 1.5% with a band width from 0 to 10.4%. Most statis ti cal mod el ing is based on the as sumption of a nor mal dis tri bu tion. The distri bu tion of the VAS and the TTO data TTO Ger many TTO UK Mean ±SD n Mean ±SD ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.41 was an a lyzed sep a rate ly. The nor mal distri bu tion was sta tis ti cal ly plau si ble (Kolmogrov-Smir nov tests, Lil liefors) in 9 of 36 VAS val ues and in 6 of 35 TTO values. While less se vere health states are rather neg a tive ly skewed (the me di an is high er than the mean), health states with se ri ous prob lems are rather pos i tively skewed. Valuation results As seen in. Table 3, the av er age val ues of VAS are par tic u lar ly even ly dis tribut ed and dif fer slight ly from the data of the German postal sur vey in Fur ther more, the VAS val ues are close ly re lat ed to the British VAS val ues us ing the same pro tocol (see [8]). Com par i son of the TTO results, on the oth er hand, shows clear dif ferences be tween the Ger man and the British stud ies. The TTO val ues of the Ger man study are high er in all health states, with 30 of 35 health states sta tis ti cal ly sig nif i- cantly higher (P<0.05, one-sam ple t test). Modeling The cal cu la tion with the ad di tive linear model resulted in installments for restric tions in di cat ed in the di men sions as shown in. Table 4. The re gres sion co effi cients of the vari ables UA, AD, S2, and U2 were not significantly different from 0. Ad di tion al ly, and against the log ic of the mod el, the re gres sion co ef fi cient of the vari able U2 showed a pos i tive val ue. Therefore a sec ond cal cu la tion was made without nonsignificant variables. The R 2 of this model (R 2 =0.51) was comparable to that in the British study (R 2= 0.46). None of the models which permitted interactions between the different dimensions improved the sig nif i cance of the mod el, and they even caused many in con sis ten cies. The result ing re gres sion equa tion be came (see also. Table 4): Y=a+β 1 MO+β 2 SC+β 4 PD+β 6 M2+β 9 P2 +β 10 A2+β 11 NE. Note that the con stant de vi ates sig nif i cantly from 0. That means that the val ue of full health (11111) is less than 1.00, due to less than per fect spec i fi ca tion of the model. As the the o ret i cal val ue of full health is known, should be as so ci at ed with the val ue of 1.00, as ad vised by the British in ves ti ga tors [7]. With the help of the re gres sion co ef fi cients all val ues of the EQ-5D can be es ti mat ed: the Ger man EQ-5D Index is than avail able. For ex am ple, 128 Eur J Health Econom

6 . Table 5 gives the cal cu la tion of the EQ- 5D Index for the health state Ta ble 6 shows the in di vid u al misspec i fi ca tion of the lean mod el over the full range of health states. Some dif ferences stand out: 11211, 11112, 11113, 12223, 11131, 11133, 21232, 22331, and Discussion Summary results Ad min is ter ing 334 face-to-face TTO in terviews produced societal values for 36 EQ- 5D health states. By re gres sion anal y sis we then estimated values for all 243 theoretical ly pos si ble EQ-5D health states and estab lished a Ger man EQ-5D Index based on TTO val ues. The TTO val ues in this study deviate from those in a similar investigation in the Unit ed King dom, which un derpins the need for a na tion al tar iff, such as the Ger man tar iff de vel oped in this in vestigation. Critical appreasel of conclusions We did not strat i fy the re sults for pos sible nonrepresentativeness of sex and age. In an oth er in ves ti ga tion we ex per i ment - ed with ad just ment on the ba sis of many back ground vari ables, but the re sults hardly dif fered [6]. Tsuchiya et al. [12] also found hard ly any dif fer ences (0.008 on av er age) when they weight ed the scores of so cio-de mo graph ic vari ables in their sam ple. The full mod el showed signs of misspec i fi ca tions, like ly due to skewedness of the data, heteroscedasticity, and multicollinear i ty. Us ing a lean mod el al lowed us to avoid il log i cal steps in the re sult ing in dex score. Bra zier et al. [3] used this strate gy in their ef forts to at tribute stan dard gam ble scores to the SF-36. There is of course a price to pay: if a pa tient s qual i- ty of life chang es from one lev el to an other, and the co ef fi cients for that step have been re moved, the in dex score does not change. By mak ing a lean and con sis tent mod el the in dex be comes in sen si tive to these chang es. In oth er words, re mov ing coefficients to improve the validity of the mod el must be bal anced by the sen si tiv i- ty of the in stru ment. We hoped to have found the right bal ance in this trade-off by removing only the statistically nonsignifi cant co ef fi cients. The test as to whether we have in deed suc ceed ed in find ing the right bal ance will fol low from clin i cal investigations in which the sensitivity of our Ger man tar iff is com pared to that of the British or oth er tar iffs. The individual misspecification of the lean mod el over the full range of health states, as shown in. Table 6, gives some ad di tion al in for ma tion about the va lid i- ty of the mod el. The dif fer ences in this investigation are greater than those in vali da tion stud ies car ried out with a larg er number of respondents. The obvious expla na tion is the low er num ber of re spondents and the omit ted co ef fi cients. As expect ed, large in di vid u al dif fer ences appear at and 11112, which are ful ly de ter mined by the omit ted co ef fi cients. Oth er de vi a tions are less easy to ex plain. It is re as sur ing that the great est de vi a tion takes place in health state 33333, one that in prac tice would be rare if not im pos sible to ad min is ter. Additional interpretation of results The VAS-data from the pres ent study devi at ed from the VAS-val ues found in the Ger man postal sur vey in This is consis tent with oth er find ings in which the postal VAS val ues dif fer from VAS values elicit ed with the MVH-pro to col [8]. A possible explanation is given by Busschbach et al. [5] who found that postal admin is tra tion in cludes fram ing ef fects because the states are on fixed po si tions on the postal ques tion naire. When the states are not fixed but pre sent ed on cards, as in the present investigation, these framing effects disappear. Implication for theory It is puz zling what could be the cause of the dif fer ences be tween the TTO val ues in the pres ent Ger man val i da tion study and those in the ear li er British study. In prepar ing for this study con sid er able effort was made to ex clude tech ni cal dif ferences be tween the pres ent study and the British. Small dif fer ences of course persist ed, but it is dif fi cult to see how these small dif fer ences can ex plain an up wards shift in the TTO val ues. Ob vi ous ly the in- Table 4 Regression coefficients Variable Germany UK Full model Lean model α 0.999* 0.999* MO 0.100* 0.099* SC 0.067* 0.087* UA PD 0.114* 0.112* AD M * 0.129* S U P * 0.091* A * 0.065* N * 0.323* R *P<0.01 Table 5 Calculation of the EQ-5D Index for the health state Deviation from full health, constant a Mobility At level 2 (1 MO) Self-care At lev el Usual activities At level Pain/discomfort At level 3 (2 PD+1 P2) Anxiety/ depression N3: if any lev el is on 3 Estimated value At lev el 3 (1 A2) tercultural differences are far more important for TTO valuations than previously assumed, while VAS val ues are rather ro bust against cultural differences. This stresses the need for na tion al ly based tar iffs with in stru ments such as the EQ-5D re gard ing TTO val ues. Conclusion: implication for practice To sum ma rize, the lean mod el pre sented here can be used to at tribute Ger man Eur J Health Econom

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