Supporting information for Systematic review reveals limitations of studies evaluating health-related quality of life after potentially curative

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1 Supporting information for Systematic review reveals limitations of studies evaluating health-related quality of life after potentially curative treatment for esophageal cancer Supplement Material 1 Supplement Material 2 Supplement Material 3 Search Strategy Quality assessment criteria Quality assessment results

2 Supplement Material 1: Search Strategy "Esophageal cancer", (Esophagus cancer OR esophageal neoplasms [MeSH Terms] OR esophageal cancer [All fields] OR oesophageal cancer [All fields] OR barrett esophagus [MeSH Terms]); "surgery", (esophagectomy [All Fields] OR esophagectomy [MeSH Terms] OR surgery [Text Word]); "combined therapy", (combined modality therapy [MeSH Terms] OR combined modality therapy [Text Word] OR neoadjuvant therapy); "radiotherapy", (radiotherapy [MeSH Terms] OR radiotherapy [Text Word] OR radiotherapy adjuvant [Text Word]); "chemotherapy", (chemotherapy [Text Word] OR chemotherapy adjuvant [Text Word] OR definitive chemoradiation [Text Word] OR chemoradiotherapy OR chemoradiation); "Quality of Life", (quality of life [Mesh Terms] OR quality of life [Text word] OR Health-Related Quality of Life OR qol [Text Word] OR hrql [Text Word] ; "patient reported outcomes", (patient reported outcome [All Fields] OR outcome assessment (health care) [MeSH Terms] OR questionnaire [Text Word]).

3 Supplement material 2: Quality assessment criteria Assessment of study design Oxford Centre for Evidence-Based Medicine (CEBM) 2011 Levels of Evidence # 2.1 Question: What are the treatment harms? Level 1 Systematic review of randomized trials or n-of-1 trial. Level 2 Randomized trial or observational studies with dramatic effect. Level 3 n-randomized controlled cohort / follow-up study Level 4 Case-series, case-control studies, historically controlled studies, or cross-sectional studies Level 5 Mechanism-based reasoning Assessment of risk of bias The Cochrane Collaboration s tool for assessing risk of bias V Criteria specified below are derived from the Cochrane Handbook V5.1.0 Selection Bias (Systematic differences between baseline characteristics of the groups that are compared) Domain Description Risk Requirement Sequence Generation Low The investigators describe a random component in the sequence generation process. The method used to generate the allocation sequence is described in sufficient detail to allow an assessment of whether it should produce comparable groups "Was the allocation sequence adequately generated?" High Insufficient information about the sequence generation process to permit judgement of Low risk or High risk. The investigators describe a non-random component in the sequence generation process. Other non-random approaches usually involve judgement or some method of non-random categorization of participants. Allocation Concealment The method used to conceal the allocation sequence is described in sufficient detail to determine whether intervention allocations could have been foreseen in advance of, or during, enrolment. Low Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: Central allocation (including telephone, web-based and pharmacy-controlled randomization); Sequentially numbered drug containers of identical appearance; Sequentially numbered, opaque, sealed envelopes.

4 "Was allocation adequately concealed?" High Insufficient information to permit judgement of Low risk or High risk. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement for example if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed. Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on: Alternation or rotation; Date of birth; Case record number; Any other explicitly unconcealed procedure. Performance Bias (Systematic differences between groups in the care that is provided, or in exposure to factors other than the interventions of interest) Domain Description Risk Requirement Blinding (participants/ personnel) All the measures used, if any, to blind study participants and personnel from knowledge of which intervention a participant received are described. Information is provided relating to whether the intended blinding was effective "Was knowledge of the allocated intervention adequately prevented during the study?" Low High Attrition Bias (Systematic differences between groups in withdrawals from a study) Domain Description Risk Requirement blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding. Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken. Insufficient information to permit judgement of Low risk or High risk'. The study did not address this outcome. blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding.blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.

5 Incomplete outcome data - HRQL The completeness of outcome data for each main outcome, including attrition and exclusions from the analysis are described. Attrition and exclusions were also reported as are the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions, and any re-inclusions in analyses performed by the review authors. "Were incomplete outcome data adequately addressed? Low missing outcome data; Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; For cross-sectional studies; risk of bias was low if the compliance rate was equal and reasons for missing data was similar. Missing data have been imputed using appropriate methods. Insufficient reporting of attrition/exclusions to permit judgement of Low risk or High risk (e.g. number randomized not stated, no reasons for missing data provided);the study did not address this outcome. High Any one of the following: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; As-treated analysis done with substantial departure of the intervention received from that assigned at randomization; Potentially inappropriate application of simple imputation Detection Bias (Systematic differences between groups in how outcomes are determined) Domain Description Risk Requirement Blinding of Outcome assessment - HRQL Low All the measures used are described and, if any, the measures used to blind outcome assessors from knowledge of which intervention a participant blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken. Insufficient information to permit judgement of Low risk or High risk ; The study did not address this outcome

6 received. Information is provided relating to whether the intended blinding was effective. Do outcome assessors have knowledge of the allocated intervention? High blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; Blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding. Reporting Bias (Systematic differences between reported and unreported findings) Domain Description Risk Requirement Selective outcome reporting The possibility of how selective outcome reporting was examined is stated by the review authors, and what was found. Low If all domains and symptoms of the HRQL questionnaires were mentioned, in either text, graphs or a table. Insufficient information to permit judgement of Low risk or High risk. It is likely that the majority of studies will fall into this category. "Are reports of the study free of suggestion of selective outcome reporting?" High If a single HRQL domain of symptom was measures, yet not mentioned in the results as either text, graph or a table. Other Sources of Bias Domain Description Risk Requirement Other Sources Any important concerns about bias not addressed in the Low The study appears to be free of other sources of bias. of Bias other domains in the tool are stated. If particular There may be a risk of bias, but there is either: questions/entries were prespecified in the review s Insufficient information to assess whether an important risk of bias exists; or protocol, responses should be Insufficient rationale or evidence that an identified problem will introduce bias. provided for each High There is at least one important risk of bias. For example, the study: question/entry Had a potential source of bias related to the specific study design used Was the study apparently free of other problems that could put it at a high risk of bias? Has been claimed to have been fraudulent; or Had some other problem (e.g. no control for multiple testing [P<0.01], inclusion/exclusion criteria not the same for both groups, funding sources) Selection Bias in Observational Studies (Systematic differences between baseline characteristics of the groups that are compared). Criteria specified by the authors. Domain Description Risk Requirement Confounding Did the study describe, Low In comparison studies, if groups were compared for age, sex, disease severity (i.e., TNM) and HRQL at baseline (if consider, measure and baseline was measured) and when discrepancies, if found, were taken into account. In one-group studies, age, sex, and

7 include confounding factors in the study analysis? High disease severity were taken into account. If it was unclear if potential confounding of age, sec, disease severity and or baseline HRQL was explored or unclear whether discrepancies were taken into account If potential confounding of sex, age, disease severity and HRQL at baseline (if applicable)was not explored and or if differences between groups were not taken into account. Assessment of HRQL outcome reporting Criteria as specified by the Efficace Minimum Standard Checklist, unless otherwise stated indicated by *. The answer 'unclear' was specified by the authors. HRQL Issue Answer Requirement Conceptual Is an a priori hypothesis If authors had a predefined HRQL endpoint and/or stated expected changes due to the specific treatment. stated? If the study was not exploratory and no hypothesis was stated. When an a priori hypothesis was not clearly reported N/A When a study states an exploratory HRQL evaluation or comparison. Is a rationale for choice of questionnaire(s) reported? Measurement Is the used questionnaire reported to be culturally validated for the specific study population? Is the coverage of questionnaire domains adequate? Methodology Is there an explicit statement who filled out the questionnaire? N/A When authors justified or explained their choice for selecting a specific HRQL questionnaire. When the author did not justify or explain their choice for selecting a specific HRQL questionnaire. When a rationale was not clearly reported If the measure was validated for the specific study population and this was referenced, or explicitly mentioned, in the text. Validated generic cancer instruments were assessed as yes. If the questionnaire was not culturally validated for the specific study population or if an article failed to provide at least a reference regarding the cultural validity of the questionnaire applied. Validated disease-specific instruments were validated as no if a different cancer site was assessed. If it was unclear whether the psychometric properties were applicable to the cultural validity of the used questionnaire. If the HRQL measure is validated in the same population as the one of the study. If a validated esophageal-specific questionnaire was used. If only a HRQL generic questionnaire was used or non-validated esophageal specific items were added. If it was explicitly stated who filled in the questionnaire If the sentence implied that a patient filled in the questionnaire, yet this was not explicitly reported in the text. (i.e., we used a self-report questionnaire) Is baseline compliance If authors reported the numbers, or percentages, of patients that filled in the HRQL questionnaire at baseline (i.e. pre-treatment) reported?! If no information was reported on the baseline compliance.

8 Is the timing of the questionnaire assessment during the study specified? N/A If it was unclear how many patients complied at baseline If a study did not implement a baseline HRQL assessment point. If the authors reported the specific timing of HRQL assessment (e.g. weeks, months, years). For cross-sectional studies; mean/median and range of follow-up should be specified. If no information was reported with regards to the specific timing of HRQL assessment. If the authors reported when HRQL was assessed, but did not explicitly mention the time frame (i.e., range). For cross-sectional studies, timing of questionnaire assessment was unclear if a range was not provided. Are reasons for missing If author s report the specific reason(s) for missing data (e.g. death, administrative errors) data documented?! If no information was reported regarding the specific reasons for missing data. If the reason for missing data was unclearly documented N/A If there were no missing data Interpretation Are clinical significances addressed? If the study addresses the clinical significance of the HRQL outcomes from the patient's perspective (e.g. effect size, minimally important difference) and not simply the statistical significance If no information was stated regarding the clinical significance of HRQL results. Is there a presentation of If authors discussed the HRQL outcomes giving any comments regardless of the results (either expected or not). the results in general? If the authors did not discuss HRQL outcomes in general or at all.! This item is mandatory for robust HRQL reporting for RCT's and longitudinal studies. For cross-sectional studies, reasons for missing data was deemed mandatory Assessment of additional HRQL outcome criteria Items developed by Efficace and identified in Pachler et al. Quality of life after rectal resection for cancer, with or without permanent colostomy HRQL Issue Answer Requirement Is a test of statistical If the statistical test applied is specifically reported in the text. significance for HRQL applied? If no statistical test was applied If a p value is reported, yet it is unclear which statistical test was used. Is there a HRQL difference between treatment arms reported? Is there an exploration of missing data? N/A N/A If a study shows at least a significant (statistical or clinical) difference in one HRQL domain, at any given time point, between pre-defined (i.e., described in the aims) treatments arms If no differences between treatment arms were reported (i.e., not for a domain or symptom, nor for any specific time-point). If there is only one pre-defined treatment arm or if a treatment arm is compared with a reference group. If an exploration for potential differences in characteristics has been reported, between those who participated and those who were lost to follow-up. If there was no exploration for differences between responders and non-responders or if differences were not taken into account. If there were no missing data reported

9 Assessment of additional issues of reporting and methodology Criteria based on the Newcastle-Ottowa Quality Assessment Scale en further specified by the authors. Issue Answer Requirement Was the study population When age, sex, disease severity (i.e.,tnm staging), and baseline HRQL (if applicable) are reported for all groups. comprehensively If no information was reported for age, sex, disease severity or baseline HRQL (if applicable). described? If age, sex, disease severity and baseline HRQL(if applicable) are reported for the total group and not for the subgroups. Were inclusion and exclusion criteria reported? Were primary (and if applicable) secondary outcomes defined? If inclusion and exclusion criteria are reported. If inclusion and exclusion criteria are not reported. If either the inclusion or exclusion criteria are reported. If the HRQL outcome is explicitly defined as either primary or secondary. If HRQL was not mentioned as an outcome. If it was unclear whether HRQL was a primary or secondary outcome. Was the intervention / treatment clearly described? Was the sample size at the first assessment point N 26 for each group? If a clear description of the treatment was reported (e.g. type(s) of surgery, type of chemotherapy/radiotherapy). If a global description of the treatment was reported (e.g. surgery instead of 'transhiatal surgery') If the number of patients in a group at first assessment was higher or equal to 26. If the number of patients in a group at first assessment was lower than 26. If it was unclear how many patients were included in a group at baseline. Was the sample size of a group N 26 for all assessments? Was the first time questionnaire compliance reported? Were follow-up rates / compliances reported? Were the follow-up compliance rates 80%? N/A If N 26 at each time point assessed. If N<26 for at least one of the time-points assessed. If it was unclear how many patients were included for HRQL analyses at each time-point specified, or for each group included. If the compliance rate of the first questionnaire assessment is specified. If questionnaire compliance was not reported for the first HRQL assessment If questionnaire compliance is unclearly reported (e.g., no numbers or percentages provided) If the questionnaire compliance was reported for each time point, and each subgroup. If no information regarding follow-up compliance was reported. If the follow-up compliance was not specified for each time point and/or each sub-group. If there was no follow-up assessment If it was reported that for each time point assessed the follow-up compliance rate of those still eligible, (e.g. exclusion of deceased) was 80% for all groups assessed.

10 Was there a sample size calculation for HRQL outcome? Did studies control for multiple testing? If at any given time-point, for any specific group, the follow-up rate was below 80% of eligible (e.g., exclusion of deceased) If there was a report for the total follow-up compliance, but not for the specific subgroups. If the total questionnaire compliance was 80%, yet the compliance rate was not specified for each subgroup, this criterion was assessed as unclear. N/A If there was no follow-up assessment If a sample size calculation for HRQL was reported. If sample size calculation for HRQL was not reported If it was unclear if the sample size calculation reported was for HRQL N/A If it was clearly reported that HRQL is not a primary outcome. If they applied a p value of 0.01, if they applied criteria for clinical significance, or if they used a statistical technique to control for multiple testing If they applied a p value of 0.05, or did not use a statistical technique to control for multiple testing. If they applied a test of statistical significance, but it was unclear which p value was used. N/A If they did not apply significance testing

11 Supplement material 3: Quality assessment results Table 2. Risk of Bias Blinding Patient/ Personnel Incomplete outcome data Selective outcome Reporting Other sources of bias First Author Sequence generation Allocation concealment Blinding outcome Randomized Controlled Trials Zhang Low Low Low Low Low Low N/A de Boer Low Low Low Low Low N/A Kachnic Low High High N/A Teoh Low High High N/A Gawad Low High High N/A Zieren High Low High High High N/A Cohort studies Avery High High High High High Low Low Barbour High High High Low High Low High High Reynolds High High High High High Low Low High Blazeby High High High High High Low High High Brooks High High High High Low High High Blazeby High High High High High Low High High O'Hanlon High High High High High High High High Wang High High High High Low Low Low Wang High High High High Low Low Low Schneider High High High High Low High High Egberts High High High High Low High High Gradauskas High High High High High High High Case-series Djarv N/A N/A N/A N/A High Low Low Low Gilham N/A N/A N/A N/A High High Low High v. Meerten N/A N/A N/A N/A High Low Low High Lagergen N/A N/A N/A N/A High Low High High Knippenberg N/A N/A N/A N/A High Low High High Parameswan N/A N/A N/A N/A High Low Low High Servagi-Vernat N/A N/A N/A N/A High High High High Safieddine N/A N/A N/A N/A High High Low High Leibman N/A N/A N/A N/A High High High High Tan N/A N/A N/A N/A High Low High High Luketich N/A N/A N/A N/A High High Low High Sweed N/A N/A N/A N/A High High High High Zieren N/A N/A N/A N/A High High High High Case-Control Hallas N/A N/A N/A N/A High Low High Low Cross-sectional - two group studies Hurmuzlu High High High High Low High High Rosmolen High High High Low High Low Low Low Schembre High High High High Low High Low Ariga High High High High High High Low Low Confounding

12 Yamashita High High High High Low High Low Rutegard High High High High High Low Low Nakamura High High High Low High Low Higuchi High High High High Low High High Viklund High High High Low High High High Low Cense High High High Low High High High High Schmidt High High High High High High Low Spector High High High Low High Low High High Blazeby High High High Low High Low Low High Cross-sectional - one group studies Courrech- Staal N/A N/A N/A N/A High Low Low High Gockel N/A N/A N/A N/A High Low Low High Pennathur N/A N/A N/A N/A High Low Low High Martin N/A N/A N/A N/A High High Low Low Chang N/A N/A N/A N/A High High Low High Moraca N/A N/A N/A N/A High Low Low High Verschuur N/A N/A N/A N/A High High High High Viklund N/A N/A N/A N/A High Low Low High Deschamps N/A N/A N/A N/A High Low High High Deschamps N/A N/A N/A N/A High Low High Low Olsen N/A N/A N/A N/A High Low High High Tabira N/A N/A N/A N/A High High High High Headrick N/A N/A N/A N/A High Low Low High de Boer N/A N/A N/A N/A High High High High Stein N/A N/A N/A N/A High High High High McLarty N/A N/A N/A N/A High Low Low High Zieren N/A N/A N/A N/A High High High High High (%) 25/31 25/31 25/31 5/31 57/62 26/62 37/62 41/56 (81%) (81%) (81%) (16%) (92%) (42%) (60%) (73%) Low (%) 2/31 2/31 2/31 11/31 1/62 36/62 25/62 15/56 (6%) (6%) (6%) (36%) (2%) (58%) (40%) (27%) (%) 4/31 4/31 4/31 15/31 4/62 0/56 (13%) (13%) (13%) (48%) (6%) (100%) N/A (%) 31/62 50%) 31/62 (50%) 31/62 (50%) 31/62 (50%) 6/62 (7%)

13 Tab 3. Quality of HRQL outcome reporting Rationale Questionnaire First Author A priori hypothesis Cultural validity Coverage domains Explicit statement Baseline compliance Timing assessment Clinical Sign. Robust Reporting a Test Sign. HQQL difference Randomized Controlled Trials Zhang N/A N/A N/A N/A de Boer N/A Kachnic N/A Teoh N/A Gawad N/A N/A N/A Zieren Cohort studies Avery N/A Barbour N/A Reynolds N/A Blazeby N/A Brooks N/A Blazeby N/A O'Hanlon N/A Wang N/A Wang N/A Schneider N/A Egberts N/A yes Gradauskas N/A Case-series Djarv N/A N/A Gilham N/A v. Meerten N/A N/A Lagergen N/A N/A Knippenberg N/A N/A Parameswan N/A N/A Servagi- Vernat N/A N/A Safieddine N/A N/A Leibman N/A N/A Tan N/A N/A Luketich N/A Sweed N/A N/A Zieren N/A N/A Case-control studies Hallas N/A N/A N/A Cross-sectional studies with a comparison group Hurmuzlu N/A Rosmolen N/A N/A Schembre N/A N/A Ariga N/A Yamashita N/A N/A Rutegard N/A Nakamura N/A N/A Reasons missing data Results in general Exploration missing data

14 Higuchi N/A N/A Viklund N/A N/A Cense N/A N/A N/A Schmidt N/A Spector N/A N/A Blazeby N/A N/A N/A Cross-sectional studies without a comparison group Courrech-staal N/A N/A N/A Gockel N/A N/A N/A N/A Pennathur N/A N/A N/A Martin N/A N/A Chang N/A N/A N/A Moraca N/A N/A N/A Verschuur N/A N/A N/A Viklund N/A N/A N/A Deschamps N/A N/A N/A Deschamps N/A N/A N/A Olsen N/A N/A N/A Tabira N/A N/A Headrick N/A N/A N/A de Boer N/A N/A N/A N/A N/A Stein N/A N/A N/A McLarty N/A N/A N/A Zieren N/A N/A N/A (%) (%) (%) N/A (%) 4/14 (29%) 9/14 (64%) 1/14 (7%) 48/62 (77%) 21/62 (34%) 41/62 (66%) 54/62 (88%) 4/62 (6%) 4/62 (6%) 38/62 (61%) 24/62 (39%) 35/62 (56%) 27/62 (44%) 17/28 (61%) 6/28 (21%) 5/28 (18%) 34/62 (55%) 46/62 (74%) 2/62 (3%) 14/62 (22%) 25/56 (45%) 25/56 (45%) 6/56 (11%) 6/62 (10%) 14/62 (23%) 48/62 (77%) 59/62 (95%) 3/62 (5%) 26/62 (42%) 36/62 (58%) 53/62 (85%) 8/62 (13%) 1/62 (2%) 29/31 (94%) 2/31 (6%) 0/31 31/62 (50%) 7/56 (12%) 49/56 (88%) 0/56 6/62 (10%)

15 Tab. 4 Additional issues of reporting and methodology Inclusion/ exclusion criteria Primary/ secondary outcomes Description treatment reported Initial questionnaire compliance reported Follow-up compliance reported Follow-up compliance 80% N 26 First point N 26 All points Sample size calculation Control Multiple Testing First author Description population Randomized Controlled Trials Zhang de Boer N/A Kachnic N/A Teoh N/A Gawad N/A N/A Zieren N/A Cohort studies Avery Barbour Reynolds Blazeby Brooks Blazeby O'Hanlon Wang Wang Schneider Egberts Gradauskas Case-series Djarv Gilham v. Meerten Lagergen Knippenberg Parameswan Servagi-Vernat N/A N/A Safieddine Leibman N/A Tan Luketich Sweed Zieren Case-control studies Hallas N/A N/A Cross-sectional with a comparison group Hurmuzlu N/A N/A Rosmolen N/A N/A Schembre N/A N/A Ariga N/A N/A Yamashita N/A N/A Rutegard N/A N/A Nakamura N/A N/A

16 Higuchi N/A N/A Viklund N/A N/A Cense N/A N/A Schmidt N/A N/A Spector N/A N/A Blazeby N/A N/A Cross-sectional without a comparison group Courrech-Staal N/A N/A Gockel N/A N/A Pennathur N/A N/A N/A N/A Martin N/A N/A Chang N/A N/A N/A Moraca N/A N/A Verschuur N/A N/A Viklund N/A N/A Deschamps N/A N/A Deschamps N/A N/A Olsen N/A N/A Tabira N/A N/A N/A Headrick N/A N/A de Boer N/A N/A Stein N/A N/A McLarty N/A N/A Zieren N/A N/A (%) (%) (%) N/A (%) 45/62 (73%) 14/62 (22%) 3/62 (5%) 49/62 (79%) 12/62 (19%) 1/62 (2%) 12/62 (19%) 35/62 (57%) 15/62 (24%) 36/62 (58%) 26/62 (42%) 44/62 (71%) 9/62 (15%) 9/62 (14%) 12/30 (40%) 8/30 (27%) 10/30 (33%) 32/62 (52%) 10/30 (33%) 10/30 (33%) 10/30 (33%) 32/62 (52%) 35/62 (56%) 26/62 (42%) 1/62 (2%) 3 (48%) 28/62 (45%) 4/62 (7%) 0/55 54/55 (98%) 1/55 (2%) 7/62 (11%) 11/58 (19%) 43/58 (74%) 4/58 (7%) 4/62 (6%)