Martin Nikolaus Dichter 1,2*, Eva-Maria Wolschon 3, Christian G. G. Schwab 1,2, Gabriele Meyer 4 and Sascha Köpke 3

Transcription

1 Dihter et al. BMC Geriatris (2018) 18:145 RESEARCH ARTICLE Item distribution and inter-rater reliability of the German version of the quality of life in Alzheimer s disease sale (QoL-AD) proxy for people with dementia living in nursing homes Open Aess Martin Nikolaus Dihter 1,2*, Eva-Maria Wolshon 3, Christian G. G. Shwab 1,2, Gabriele Meyer 4 and Sasha Köpke 3 Abstrat Bakground: The Quality of Life in Alzheimer s disease sale (QoL-AD) is a widely used Health Related Quality of Life (HRQoL) instrument. However, studies investigating the instrument s inter-rater reliability (IRR) are missing. This study aimed to determine the item distribution and IRR of the German proxy version of the QoL-AD (13 Items) and a nursing home-speifi instrument version (QoL-AD NH, 15 Items). Methods: The instruments were applied to 73 people with dementia living in eight nursing homes in Germany. Individuals with dementia were assessed two times by blinded proxy raters. The IRR analyses were based on methodologial riteria of the quality appraisal tool for studies of diagnosti reliability (QAREL), the COSMIN group and the single-measure Intra-Class Correlation Coeffiient (ICC) for absolute agreement Results: All items for both instrument versions demonstrated aeptable item diffiulty, with the exeption of one item (QoL-AD proxy). The IRR was moderate for the QoL-AD (ICC: 0.65) and insuffiient for the QoL-AD NH (ICC: 0.18). The additional omputation of the average measure ICC for two proxy-raters demonstrated a strong IRR (ICC: 0.79) for the QoL-AD and a weak IRR for the QoL-AD NH (ICC: 0.31). The detailed analysis of the IRR for eah item underpinned the need for the further development of both instruments. Conlusions: The unsatisfatory IRRs for both instruments highlight the need for the development of a user guide inluding general instrutions for instrument appliation as well as definitions and examples refleting item meaning. Priority should be given to the development of reliable proxy-person versions of both instruments. Trial registration: ClinialTrials.gov: NCT , Dateofregistration: Keywords: Quality of life, Nursing homes, Dementia, Psyhometri properties, Reliability Bakground Health Related Quality of Life (HRQoL) has beome an important outome in dementia researh [1, 2]. HRQoL is defined as a multidimensional onept that reflets the individual s subjetive pereption of the impat of a health * Correspondene: Martin.Dihter@dzne.de 1 German Center for Neurodegenerative Diseases (DZNE), Stokumer Straße 12, Witten, Germany 2 Shool of Nursing Siene, Witten/Herdeke University, Stokumer Straße 12, Witten, Germany Full list of author information is available at the end of the artile ondition on everyday living [3]. The Quality of life in Alzheimer s Disease (QoL-AD) sale has been widely used to measure HRQoL in people with dementia [4 7]. The QoL-AD has been developed in the US [4] andisbasedon the oneptual work by Lawton [8] who defines the QoL onept as multidimensional, inluding subjetive (e.g., pereived QoL and psyhologial well-being) and objetive omponents (e.g., behavioral ompetene and environment). The instrument had originally been developed as self-rating version for ommunity-dwelling people with The Author(s) Open Aess This artile is distributed under the terms of the Creative Commons Attribution 4.0 International Liense ( whih permits unrestrited use, distribution, and reprodution in any medium, provided you give appropriate redit to the original author(s) and the soure, provide a link to the Creative Commons liense, and indiate if hanges were made. The Creative Commons Publi Domain Dediation waiver ( applies to the data made available in this artile, unless otherwise stated.

2 Dihter et al. BMC Geriatris (2018) 18:145 Page 2 of 11 dementia but has also been used frequently as proxy-instrument in the nursing home setting [9 11]. In addition to the self- and proxy version of the QoL-AD, Edelman et al. [5] have developed the QoL-AD NH, an adapted version of the original instrument partiularly for people living in nursing homes. Whereas self-rating means that the QoL of a person with dementia is rated by herself/himself, a proxy-rating is defined as the QoL rating of a partiular person with dementia by a proxy e.g. relative or aregiver of the person with dementia. Aording to Pikard & Knight [12] the proxy-rating perspetives proxy-proxy and proxy-person have been distinguished. While in the former perspetive the proxy rates the HRQoL of a person with dementia from his/her proxy perspetive, in the latter perspetive a proxy assesses the QoL of a person with dementia as he/she thinks the person with dementia would rate him or herself [12]. Both proxy perspetives are appropriate for the assessment of HRQoL. Unfortunately, the applied proxy perspetive mostly remains unlear in the literature [13]. One reent study investigated both perspetives (proxy-proxy and proxy-person), omparing them to self-reports of people with and without dementia in nursing homes. The three perspetives were assessed with different versions of the EuroQol-5D [13]. The results show that both proxy-perspetives overestimate low self-reports and underestimate high self-reports. The tendeny to attenuate self-ratings existed for both proxy-perspetives with a smaller perspetive gap between self-ratings and the proxy-person perspetive [13]. These results highlight the need for a lear definition and desription and the psyhometri investigation of both proxy perspetives. In general, there is little information on the psyhometri properties of the proxy versions of the QoL-AD and QoL-AD NH [1, 2]. In partiular, there is a lak of information about the inter-rater reliability (IRR) of the QoL-AD proxy and QoL-AD NH proxy sales [2]. This lak of information is often negleted in the literature [1, 14 18] and its impat on the validity of the QoL-AD proxy and QoL-AD NH proxy sales is unlear [19]. A detailed user guide with instrutions for the instrument appliation is available for the self-rating versions, but not for proxy-rating versions. It is partiularly unlear whether the items of both proxy versions have to be rated from a proxy-proxy or a proxy-person perspetive. QoL-AD proxy and QoL-AD NH proxy are frequently applied whih is most likely due to the instruments antiipated feasibility. Thus, the low number of items (QoL-AD proxy = 13 Items, QoL-AD NH proxy = 15 Items) and the fat that no omprehensive training is neessary (instrutions for the proxy versions are not available) allows a resoure-saving data olletion in ontrast to other QoL measures for people with dementia (e.g. QUALIDEM, Dementia Care Mapping instrument). The number of missing values has been desribed as low [9, 11, 20]. The disrepany between this lak of knowledge and the unontrolled usage of the QoL-AD proxy and QoL-AD NH proxy emphasizes the relevane of a omprehensive evaluation of the IRR of both measures. While the German version of the QoL-AD proxy has been available for some years, we have only reently onduted a ross-ultural adaption of the QoL-AD NH proxy to the German ontext [21]. Based on the international lak of knowledge onerning the IRR of the QoL-AD proxy and QoL-AD NH proxy as well as different perspetive gaps between self-ratings and proxy perspetives the objetive of the present study was to evaluate item distribution and IRR of both instruments, based on a proxy-proxy perspetive for the QoL-AD proxy and a proxy-person perspetive for the QoL-AD NH proxy. Methods Study design This study was onduted between June 2015 and Marh 2016 as a nested ohort study within the randomized ontrolled trial EPCentCare [22], whih aimed to redue antipsyhoti mediation in nursing home residents. EPCentCare was arried out in three German regions, whereas the present evaluation took plae in Northern Germany only. The study sample onsisted of people with dementia from eight nursing homes loated in Shleswig-Holstein and Hamburg. The investigation of the IRR of the QoL-AD proxy and QoL-AD NH proxy was based on the riteria of the quality appraisal tool for studies of diagnosti reliability (QAREL) [23] and the COSMIN group [24] (e.g. sample size alulation, desription of blinding of raters, desription of raters). Sample size alulation The sample size alulation was based on an estimated intra-lass orrelation oeffiient (ICC) of 0.75, ratings of two independent raters (registered nurses and nursing assistants) and a width of 0.20 for the 95% Confidene Interval (CI). This resulted in a alulated sample of 75 residents with dementia [25]. Proedures Aording to the inlusion riteria of the EPCentCare trial, nursing homes with at least 50 residents were eligible for partiipation in the study. For this IRR evaluation the predefined inlusion riteria for residents with dementia was a Dementia Sreening Sale sore 3[26]. Exlusion riteria were a temporary stay in respite are or a primary diagnosis of shizophrenia or bipolar disorders.

3 Dihter et al. BMC Geriatris (2018) 18:145 Page 3 of 11 Inlusion riteria for aregivers were at least half-time work and at least one year nursing training ( nursing assistant qualifiation). Qualifiation levels of proxy-raters depended on organizational onditions and staffing levels at the time of data olletion in the partiipating nursing homes. Additionally, aregivers had to have been at work on at least seven days within the last two weeks prior to data olletion and had to have a lose relationship with the assessed resident. Based on these riteria, aregivers were identified and assigned to the assessed residents by the management staff (head nurse) of eah partiipating nursing home. The lose relationship with the assessed resident enabled the aregivers to rate the HRQoL based on a proxy-person and proxy-proxy perspetive. The IRR evaluation was based on independent proxy-ratings from registered nurses or nursing assistants referring to the preeding two weeks. Both independent ratings for one measure and one resident took plae in the same shift and under the same irumstanes. Eah aregiver was blinded to the ratings of the other rater. To ensure blinding of raters and standardized data olletion, appliation of QoL-AD proxy and QoL-AD NH proxy was supervised by researhers of the EPentCare trial, who had been trained in applying QoL instruments, prior to the data olletion. The supervision inluded a short instrution about the assessed onstrut (e.g. HRQoL, agitated behavior), the underlying time frame (preeding two weeks) and the perspetive (e.g. proxy-person). Based on different organizational onditions and staffing levels at the time of data olletion, independent ratings by different qualified aregivers (registered nurses and nursing assistants) were possible. During the data olletion oasion one aregiver assessed one QoL-AD proxy version at the beginning and one at the end of the data olletion. The order of the QoL-AD proxy appliation was randomly applied. Instruments The QoL-AD proxy onsists of 13 items whih an be answered by self-rating (person with dementia) or proxy-rating (e.g. aregiver). Response options for all items are poor, fair, good and exellent resulting in item sores between 1 to 4 and total sores between 13 and 52, with higher sores indiate higher HRQoL. In 2005 the QoL-AD was translated into German language [27]. For this investigation the German version provided by Mapi Researh Trust, Lyon was used [28]. Although information related to the linguisti validation of the German version is not available, in two reent studies, the German QoL-AD proxy demonstrated suffiient internal onsisteny and strutural validity [6, 29]. For the nursing home version (QoL-AD NH proxy), two items of the original version onerning finanial and marital status (Money, Marriage) were removed and four items added (People who work here, Ability to take are of oneself, Ability to live with others, and Ability to make hoies in one s life) [5]. The response options for the QoL-AD NH orrespond to the original version, resulting in total sores from 15 to 60. In 2016 the nursing home version was translated into German and linguistially validated [21]. While no information on psyhometri properties are available for the German version, the original US proxy-proxy version showed suffiient internal onsisteny in three studies [5, 30, 31] and a nearly perfet IRR [31]. Cognitive impairment of partiipating residents was assessed by nursing staff using the Dementia Sreening Sale (DSS) [26], a seven item measure with a three point response sale (0, 1, 2) resulting in sores between 0 and 14, with higher sores indiating more ognitive impairment. Agitated behavior was assessed by nursing staff using a adapted German version [32] of the Cohen-Mansfield Agitation Inventory (CMAI) [33, 34], a proxy-measurement onsisting of 25 items rated on a seven-point sale of frequeny of ourrene resulting in sores between 25 and 175 [35], with higher sores indiating higher frequenies of agitation. Age, gender, length of stay in nursing home in months, and are dependeny level (0, I, II, or III) as defined by the German long-term are insurane, were taken from the residents ase files. In addition, proxy-rater harateristis were assessed with single items. Data analysis Sample harateristis and item distribution were omputed using desriptive statistis. Based on the item distribution the item diffiulty was proven. An item mean in the first 20% of the sale was defined as floor effet and in the last 20% as eiling effet. To gain omprehensive information on the degree of IRR for the QoL-AD proxy and QoL-AD NH proxy, a reliability oeffiient was alulated for eah measurement item and all measurement items in total. This proedure was based on earlier IRR studies and allowed a detailed interpretation and omparison of the IRR of eah item [36, 37]. The IRR for eah item was based on a alulation of the overall proportion of agreement (p o ). Moreover, we omputed the linear weighted κ statistis for ordinal data (κ w ) [38, 39], beause p o ignores the possibility that agreement ould our only by hane and instead onsiders only rude agreement. The two paradoxial properties of κ statistis were onsidered during the interpretation of the results [40]. The interpretation of κ w values was based on the following ranges: , slight; , fair; , moderate; , substantial; and , nearly perfet [41]. The IRR of the QoL-AD proxy and QoL-AD NH proxy in total

4 Dihter et al. BMC Geriatris (2018) 18:145 Page 4 of 11 were evaluated using Intralass Correlation Coeffiients (ICC) based on a two-way random-effets model for absolute agreement. Additionally, the average-measure ICC for two raters was alulated. This oeffiient estimates the IRR of a ollaborative QoL-AD proxy respetively QoL-AD NH proxy rating by two raters. Based on the reommendation by Terwee et al. [24], we targeted κ w and ICC values 0.7. To analyze the level of unertainty, 95% CIs for ICCs and κ w values were examined. The 95% CI for κ w values was based on 10,000 bootstrapped samples and determined using the perentile method [42], whih inluded using the and perentile levels of the estimated Kappa distributions as interval limits. Statistial analysis was performed using R Version [43] and the software pakages irr Version 0.84 [44] and boot Version [45, 46]. Results Charateristis of the sample The sample onsisted of 73 residents with dementia and 21 aregivers from eight nursing homes (Table 1). Item distribution The desriptive investigation of the QoL-AD proxy items (proxy-proxy perspetive) demonstrated a balaned distribution (Table 2). The response option good was used most frequently whereas the response ategory exellent was used least often. Distributions of the other response options were balaned. Only one item showed a floor effet (item 10, ability to do hores around the house). Analyses for the QoL-AD NH proxy (proxy-person perspetive) yielded similar results. However, no item showed floor or eiling effets. Missing value analyses demonstrated low perentages of missing values in general. Only item 12 (Money) of the QoL-AD proxy showed a high perentage of missing values (29%). The main reason for this was nurses refusal to rate or a lak of knowledge to assess residents finanial situation. A desriptive omparison of the elven omparable items shows no lear pattern that one perspetive or QoL sale lead to higher QoL ratings. Inter-rater reliability The results of the IRR evaluation for the QoL-AD proxy and the QoL-AD NH proxy are displayed in Table 3. Based on the high perentage of missing values for item 12 of the QoL-AD proxy two ICC values based on different sample were omputed. Both resulting ICC values (ICC: 0.65 = 13 items, ICC: 0.63 = 12 items) demonstrated a moderate IRR for the QoL-AD proxy. The average-measure ICC for two proxy-raters demonstrated a strong IRR of 0.79 (13 items) or 0.77 (12 items) for the QoL-AD proxy. In ontrast, the IRR results for the Table 1 Charateristis of the sample Charateristis People with dementia n = 73 Age in years a (±7.71) Female a 38 (71.7%) Length of stay in nursing home in months a (±31.14) Care dependeny levels a, b None 0 (0.0%) onsiderable (= I) 9 (17.0%) severe (= II) 25 (47.2%) most severe ( III) 19 (35.8%) Dementia Sreening Sale (DSS) 9.01 (±3.14) mild or moderate dementia (3 7) 28 (38.4%) severe dementia (8 14) 45 (61.6%) Challenging behaviour (CMAI) a (±10.48) Caregivers (proxy-raters) n = 8 Age in years (±13.76) Female 8 (100.0%) Registered nurses 5 (62.5%) Working experiene in years 9.38 (±5.63) Working hours per week (±3.54) Experiene in proxy-ratings no 6 (75.0%) yes, at least one 1 (12.5%) yes, regularly ( twie a month) 1 (12.5%) Data are reported as means (±SD) or absolute number (%) a These results were based on n = 53 people with dementia, beause these harateristis were missing for n = 20 people of the total sample b As determined by expert raters of the medial servie of the statutory longterm are insurane system The analyzed data inludes answers of 21 raters. For 13 proxy-raters there are no data available Qol-AD NH proxy were weak: (0.18 or 0.31 for the average-measure ICC). For the QoL-AD proxy, κ w values ranged from 0.07 (item 12: money) to 0.55 (item 6: family). The p o ranged between 0.33 (item 12: money) and 0.63 (item 13: life as a whole). IRR results for the QoL-AD NH proxy items ranged between 0.03 (item 4: living situation) to 0.38 (item 15: live overall) for the κ w and between 0.29 (item 4: living situation) to 0.55 (item 15: live overall) for the p o. Disussion Item distribution This study desribes a omprehensive evaluation of the item distribution and inter-rater reliability of the German QoL-AD proxy and QoL-AD NH proxy. The investigation of the item distribution of the QoL-AD proxy demonstrated a balaned distribution of the four response options. Twelve out of 13 items showed an aeptable item diffiulty. Only one item

5 Dihter et al. BMC Geriatris (2018) 18:145 Page 5 of 11 Table 2 Item distribution based on two observations for eah ase German version of the QoL-AD proxy and QoL-AD NH proxy QoL-AD proxy (proxy-proxy perspetive), n = 73 QoL-AD NH proxy (proxy-person perspetive), n = 73 No. Item response options desriptive No. Item response options desriptive How do you judge poor fair good exellent missing mean (±SD) How do you think the resident would poor fair good exellent missing mean (±SD) judge his/her the physial health of the (±0.88) 1. physial health? (±0.92) 2. the energy of the (±0.90) 2. energy? (±0.81) 3. the mood of the (±0.77) 3. mood? (±0.86) 4. the living situation of the (±0.61) 4. living situation? (±0.83) 5. the memory of the (±0.74) 5. memory? (±0.90) 6. the family of the (±1.12) 6. family? (±1.01) 7. the marriage of the (±1.23) 8. the friends of the (±0.95) 7. friends? (±1.06) 9. his /herself as a whole? (±0.63) 8. -self overall? (±0.79) 10. the ability of the resident to do hores around the house? a (±0.65) 9. ability to keep busy? (±0.82) 11. the ability of the resident to do things for fun? (±0.86) 10. ability to do things for fun? (±0.77) 12. the money of the (±0.92) 11. b people who work here? (±0.75) 12. ability to take are of him /herself? (±0.96) 13. ability to live with others? (±0.77)

6 Dihter et al. BMC Geriatris (2018) 18:145 Page 6 of 11 Table 2 Item distribution based on two observations for eah ase German version of the QoL-AD proxy and QoL-AD NH proxy (Continued) QoL-AD proxy (proxy-proxy perspetive), n = 73 QoL-AD NH proxy (proxy-person perspetive), n = ability to make (±0.92) hoies in his/ her life? 13. life as a whole? (±0.61) 15. life as a whole? (±0.72) Frequenies of the response options and missing s in total n Frequenies of the n % response options and missing s in % total Qol-AD proxy sore 1 Rating (±5.72) Qol-AD NH proxy sore 1 Rating (±7.84) 2 Rating (±5.76) 2 Rating (±7.11) a Item with floor effet, i.e. mean in the first 20% of the sale (< 1.6) b The question begins with: How satisfied do you think the residents feels about the Only observations without any missing value were inluded (Qol-AD proxy: n = 39; Qol-AD NH proxy: n = 62)

7 Dihter et al. BMC Geriatris (2018) 18:145 Page 7 of 11 Table 3 Inter-rater reliability results for the German version of the QoL-AD proxy (proxy-proxy perspetive) and QoL-AD NH proxy (proxy-person perspetive) QoL-AD poxy (n = 39) f ICC (95% CI): 0.65 [0.79 ( ) a QoL-AD NH ( )] b proxy (without item 12, n = 65) ICC (95% CI): 0.63 [0.77 ( ) a ( )] b (n =62) f ICC (95% CI): 0.18 [0.31 ( ) a ( )] b No. How do you judge p o κ w (95% CI) d No. How do you think the resident would judge his/her p o κ w (95% CI) d 1. the physial health of the ( ) 1. physial health? ( ) 2. the energy of the ( ) 2. energy? ( ) 3. the mood of the ( ) 3. mood? ( ) 4. the living situation of the ( ) 4. living situation? ( ) 5. the memory of the ( ) 5. memory? ( ) 6. the family of the ( ) 6. family? ( ) 7. the marriage of the ( ) 8. the friends of the ( ) 7. friends? ( ) 9. his /herself as a whole? ( ) 8. -self overall? ( ) 10. the ability of the resident to do hores around the house? ( ) 9. ability to keep busy? ( ) 11. the ability of the resident to do things for fun? ( ) 10. ability to do things for fun? ( ) 12. the money of the ( ) 11. f people who work here? ( ) 12. ability to take are of him /herself? ( ) 13. ability to live with others? ( ) 14. ability to make hoies in his/her life? ( ) 13. life as a whole? ( ) 15. life as a whole? ( ) a Intra-lass orrelation oeffiient and orresponding 95% CI b Average-measure ICC for two raters in parentheses and orresponding 95% CI Overall proportion of agreement (the ratio of exat agreement between raters) d Linear weighted Kappa values. CIs were based on 10,000 bootstrapped samples e Item with floor effet, the mean is in the first 20% of the sale (< 1.6), see Table 2 f Complete ase analysis

8 Dihter et al. BMC Geriatris (2018) 18:145 Page 8 of 11 (item 10: ability to do hores around the house) showed a floor effet and item 12 (Money) showed a high perentage of missing values (29%). One reason for these results for item 10 and 12 might be a missing ross-ultural adaption of the QoL-AD proxy for the German ontext and in partiular for German nursing homes. The analysis for the QoL-AD NH proxy yielded similar results with an aeptable item diffiulty for all 15 items. With the exeption of the identified floor effet for item 10 of the QoL-AD proxy, these desriptive results are in the line with previous results [4, 5, 21, 47]. Given the relatively small sample size, the identified floor effet for the item 10 of the QoL-AD proxy must be interpreted with aution. A desriptive omparison of the eleven omparable items shows no lear pattern that one perspetive leads to higher QoL ratings. Thus, ompared to the omparable items rated in both perspetives, we identified higher mean values for the items 1, 2 and 4 of the QoL-AD (proxy-proxy) and for the items 3, 5, 6, 7, 8, 9, 10 and 15 of the QoL-AD NH (proxy-person). We assumed systematially higher QoL ratings based on a proxy-person perspetive ompared to a proxy-proxy perspetive. This assumption was based on previous studies, whih demonstrated systematially lower proxy-based QoL ratings ompared to self-ratings [48, 49], and on one reent study, whih showed a smaller perspetive gap between self-ratings and the proxy-person perspetive [13]. The major reason for the missing differene between both perspetives might be the only moderate to weak IRR of the applied sales and perspetives. Inter-rater reliability The IRR results demonstrate a moderate IRR for the QoL-AD proxy (ICC: 0.65, 13 items, ICC: 0.63, 12 items) and an insuffiient IRR for the QOL-AD NH (ICC: 0.18). The additional omputation of the average measure ICC for two proxy-raters demonstrated a strong IRR of 0.79 (13 items) or 0.77 (12 items) for the Qol-AD proxy and a weak ICC for the QoL-AD NH proxy (0.31). The detailed analysis of the IRR of eah item yielded heterogeneous results. Based on κ w and p o, only item 6 (family) of the QoL-AD proxy demonstrated a moderate IRR. All other QoL-AD proxy items showed fair (items 1: physial health, 2: energy, 3: mood, 5: memory, 7: marriage, 10: ability to do hores around the house, 13: life as a whole) or slight IRR (items: 4: living situation, 8: friends, 9: his /herself as a whole, 11: ability to do things for fun, 12: money). Based on the high number of missing values and the slight IRR of item 12 (money of the resident) we reommend the exlusion of this item for the QoL-AD proxy appliation in nursing homes. For the QoL-AD NH proxy only items 1 (physial health) and 15 (life overall) yielded a fair IRR. All other items demonstrated a slight IRR. The in-depth analysis of the IRR indiates the need for improvement of both instruments for their appliation in researh and pratie. An improvement of the IRR might be reahed through a strutured instrument user guide inluding lear definitions and examples related to the meaning of eah QoL-AD proxy and QoL-AD NH proxy item. The positive effet of suh a user guide has been demonstrated in a reent IRR study on the dementia-speifi QoL instrument QUALIDEM [37]. This study is the first IRR study dealing with the proxy version of the QoL-AD. Therefore, study results an only be ompared to the IRR results of other dementia-speifi QoL and HRQoL instruments [2]. The IRR of the Alzheimer Disease-Related Quality of Life (ADRQL) instrument was evaluated in two studies showing different results. While the US version of the ADRQL demonstrated exellent IRR with ICC values between 0.90 and 1.0 [31], a Swiss study identified slight to moderate ICC values depending on ADRQL subsales (Soial interation: ICC = 0.36, Awareness of self, ICC: 0.61, Feelings and mood, ICC: Enjoyment of ativities, ICC: 0.02, Response to surrounding,: ICC: 0.17) [50]. Both study results have to be interpreted with aution beause of several methodologial limitations [2]. The Quality of Life in Late stage Dementia sale (QUA- LID) demonstrated good IRR with an ICC value of 0.83 [51]. For the instrument QUALIDEM a reent study yielded a good IRR for all subsales for people with mild to very severe dementia (ICC = ) with the exeption of the subsale negative affet (ICC = 0.64) [37]. These three instruments reflet overall QoL. One frequently used instrument for the assessment of dementia-speifi HRQoL is the DEMQOL [17]. Unfortunately, no information were available on IRR of the DEMQOL proxy-version whih would have allowed a omparison to our study results [2]. Due to the heterogeneous range of QoL domains assessed with different QoL and HRQoL instruments, a omparison of IRR results between different instruments is limited. However, IRR results of instruments like QUALIDEM and QUALID demonstrate that good IRR values are ahievable for proxy-rated dementia-speifi QoL. Our IRR results for the QoL-AD NH proxy an be ompared to one previous US study whih demonstrated a high IRR with a ICC value of 0.99 [31]. In ontrast, our IRR results seem low. However, the study by Sloane et al. [31] had several methodologial limitations and a proxy-proxy perspetive. In ontrast, our results are based on a proxy-person perspetive. The different perspetives also explain the differenes between the Qol-AD proxy and the QoL-AD NH proxy in our study.

9 Dihter et al. BMC Geriatris (2018) 18:145 Page 9 of 11 A omparison of equal items (item 1 6 and 7 10) from the QoL-AD proxy and QoL-AD NH proxy show lower p o. and κ w for the items assessed with the proxy-person perspetive (QoL-AD-NH proxy). The QoL-AD proxy data were based on a proxy-proxy perspetive whih means that proxies rate the HRQoL of are reipients from their proxy perspetive. This might be an easier perspetive ompared to the so-alled proxy-person perspetive as there is no need for a perspetive shift by the proxy rater. Nevertheless, proxy-proxy ratings an also be influened by attitudes [52], life satisfation, the assessment irumstanes and hallenging behaviors of people with dementia living in nursing homes [53]. Moreover, HRQoL ratings based on proxy-proxy ratings might not be partiularly valid due to the partial loss of subjetivity of the HRQoL assessment [54]. In ontrast, the proxy-person perspetive requires a hange of perspetives. Here, a proxy assesses the HRQoL of a person with dementia as he/she thinks the person with dementia would rate him or herself. It an be assumed that this perspetive is more diffiult for proxies, thus the required level of individuality for eah HRQoL rating is high. The results of a reent study [13], whih showed a smaller perspetive gap between self-ratings and the proxy-person perspetive, underpin the need for the further development of the proxy-versions of the QoL-AD and QoL-AD NH to enable the assessment of an IRR proxy-person perspetive for both instruments. Limitations This study is the first investigation of IRR of the QoL-AD based on a proxy-proxy perspetive and the QoL-AD NH based on a proxy-person perspetive. The strengths of this IRR study are the in-depth analysis of the IRR of eah instrument item, the inlusion of people at all stages of dementia and the methodologial rigor based on the riteria of the quality appraisal tool for studies of diagnosti reliability (QAREL) as well as the COSMIN group [24]. The following limitations should be onsidered when interpreting the results. First, although the preplanned sample sizes were almost ahieved, the identified width of CIs of the omputed ICC values range between 0.29 and Espeially when interpreting the IRR of the QoL-AD NH this statistial unertainty has to be taken into aount. Our results provide a good basis for sample size alulations of further IRR studies. Seond, the applied data olletion proedure led to a QoL-AD proxy and a QoL-AD NH proxy assessment for a resident with dementia by one aregiver on one oasion. Despite the random order of the ratings a possible influene of the rating of one measure on the rating of the seond measure annot be exluded. Third, proxy-raters harateristis have to be interpreted with aution due to the high rate of missing values. Fourth, a lose relationship between the proxy and the assessed person with dementia will help proxy raters to reah this required level of individuality. Usually primary models of nursing are are used in German nursing homes. The head nurse was instruted to assign a primary nurse to the assessed residents. Unfortunately, the shortage of nurses in German nursing homes may have influened the assignment of the head nurses. A varying understanding of this riterion by the assigning head nurse may be jointly responsible for the IRR results. Conlusions This IRR study demonstrated a moderate IRR for the QoL-AD based on a proxy-proxy perspetive and an insuffiient IRR for the QoL-AD NH (proxy-person perspetive). Aording to established ut off points for the interpretation of IRR values there is a need for the improvement of both instruments. We reommend the development of a user guide inluding general instrutions for the appliation of both instruments as well as definitions and examples refleting the meaning of eah item. Priority should be given to the development of reliable proxy-person versions of both instruments. Until a user guide is available, the QoL-AD proxy might be onduted as a ollaborative rating by at least two proxy-raters. However, this approah is limited to a proxy-proxy perspetive whih means partial loss of the subjetivity of the HRQoL assessment and as a result, a redution in validity. Additionally, we reommend the exlusion of item 12 (money of the resident) for the QoL-AD proxy appliation in nursing homes. The QoL-AD NH based on a proxy-person perspetive should not be used until a user guide is available and further IRR studies have demonstrated an improved IRR. Abbreviations 95% CI: 95% Confidene Interval; ADRQL: Alzheimer Disease-Related Quality of Life; CMAI: Cohen-Mansfield Agitation Inventory; COSMIN: COnsensusbased Standards for the seletion of health Measurement Instruments; DSS: Dementia Sreening Sale; EPCentCare: Effet of person-entred are on antipsyhoti drug use in nursing homes; HRQoL: Health Related Quality of Life; ICC: Intra-lass orrelation oeffiient; IRR: Inter-rater reliability; p o : proportion of agreement; QAREL: Quality Appraisal tool for studies of diagnosti RELiability; QoL-AD NH: Quality of life in Alzheimer s Disease Nursing Home; QoL: Quality of Life; QoL-AD: Quality of life in Alzheimer s Disease; QUALID: Quality of Life in Late stage Dementia sale; κ w : weighted kappa statistis Aknowledgements We would like to thank the aregivers and the people with dementia for their partiipation in our investigation. Funding German Federal Ministry of Eduation and Researh (BMBF grant 01GY1335B). The funding body. The funders had no role in the design of the study, data olletion, analysis or interpretation of the data.

10 Dihter et al. BMC Geriatris (2018) 18:145 Page 10 of 11 Availability of data and materials All of the data neessary for a meta-analysis of inter-rater reliability of QoL- AD items are ontained within the manusript and its supplementary files. The datasets used and/or analyzed during the urrent study are available from the orresponding author on reasonable request. Authors ontributions MND, EMW, GM, and SK designed the study and developed the researh question. EMW and SK performed the data olletion. CGGS and MND arried out the data analysis. MND was responsible for the preparation of a first manusript draft; all authors (MND, EMW, CGGS, SK, and GM) ontributed to the manusript preparation. All authors have read and approved the final version of the manusript. Ethis approval and onsent to partiipate Ethial approval was obtained from the ethis ommittee of the University of Lübek (Ref ). Written information about the study was given to residents and residents legal representatives, and written informed onsent was obtained from residents or their legal representatives. Caregivers reeived written and oral information about the study before data olletion. Voluntary partiipation in the data olletion was onsidered as informed onsent from aregivers. A written onsent from the aregivers was waived by the ethis ommittee. Consent for publiation Not appliable. Competing interests All authors delare that they have no ompeting interests. GM is a member of the BMC Geriatris editorial board, but was not involved in the review proess. Publisher s Note Springer Nature remains neutral with regard to jurisditional laims in published maps and institutional affiliations. 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