An explanatory sequential mixed-methods design to establish thresholds of within-individual meaningful change on a sleep disturbance numerical rating scale score in atopic dermatitis.

PURPOSE: Establishing a meaningful within-individual change (MWIC) threshold is a key aspect for interpreting scores used as endpoints for evaluating treatment benefit. A new patient-reported outcome (PRO), a sleep disturbance numerical rating scale (SD NRS), was developed in adults and adolescents with moderate-to-severe atopic dermatitis (AD). This research aims to establish a MWIC threshold of the SD NRS score in the context of a drug development program. METHODS: An explanatory sequential mixed-methods design was used to address the research objective. This mixed-methods design used phase IIb data and a stand-alone qualitative study. Quantitative anchor-based and distribution-based approaches supported by qualitative-based approaches were conducted, and results were triangulated to determine preliminary MWIC thresholds of the SD NRS score. RESULTS: Triangulation of results from both quantitative and qualitative approaches suggested that a 2- to 6-point decrease in the SD NRS score change constitutes a preliminary range of MWIC threshold estimates. CONCLUSION: This research determined MWIC threshold estimates for the SD NRS score in both adolescents and adults with moderate-to-severe AD using an explanatory sequential mixed-methods design. This mixed-methods design provides interesting insights for establishing MWIC thresholds of a PRO score in the context of a drug development program.

Correction to: Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma.

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Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma.

BACKGROUND: No validated disease-specific questionnaires exist to capture health-related quality of life (HRQoL) in patients with Merkel cell carcinoma (MCC). The Functional Assessment of Cancer Therapy - Melanoma (FACT-M) is validated in patients with melanoma, which shares many similarities with MCC. This paper reports the psychometric properties of the FACT-M in the metastatic MCC population. METHODS: Data were collected as part of a single-arm, open-label, multicenter trial involving patients with metastatic MCC who had failed at least one previous line of chemotherapy. FACT-M and EQ-5D were administered at baseline, Week 7, Week 13, and Week 25. An optional interview was administered at the same time points. MCC-specific FACT-M scores were derived following a combined quantitative and qualitative approach. Reliability and construct validity of original and additional MCC-specific FACT-M scores were assessed at baseline. Capacity to detect change in tumor size was assessed from baseline to Week 7. Minimally important differences (MIDs) were computed using distribution and anchor-based methods. RESULTS: Baseline assessments were available in 70 patients (mean age: 70 years; 74.3% male); 19 patients were interviewed at baseline. Additional MCC-specific scores were as follows: Physical Function score (six items), Psychological Impact score (six items), and MCC summary score (12 items). FACT-M original and additional MCC-specific scores both demonstrated acceptable psychometric properties: high reliability (Cronbach's alpha: 0.81-0.96), good convergent validity (correlations above 0.4 observed for 88% of items of the Melanoma surgery scale, 75% of items of the Melanoma scale, and 100% of items of the other FACT-M domains). Some evidence of floor/ceiling effects and poor discriminant ability was found. Higher scores (better HRQoL) on all FACT-M domains were observed in patients with better functioning (assessed by ECOG performance score), supporting clinical validity. Despite the small sample for responsiveness analysis (n = 37), the majority of FACT-M scores showed sensitivity to changes in tumor size at Week 7 with small to moderate effect sizes. MIDs were consistent with previously reported values in the literature for FACT-M domains. CONCLUSIONS: FACT-M is suitable to capture HRQoL in patients with metastatic MCC, thus making it a potential candidate for assessing HRQoL in MCC trials. TRIAL REGISTRATION: This study is a post-hoc analysis conducted on data collected in Part A of the JAVELIN Merkel 200 trial. This trial was registered on 2 June 2014 with ClinicalTrials.gov as NCT02155647 .

Scoring and psychometric validation of the 'Determinants of Intentions to Vaccinate' (DIVA©) questionnaire.

BACKGROUND: Primary care physicians (PCPs) play a key role regarding vaccination in France. The aims of the present study were to define the scoring rules and to assess the measurement properties of the 'Determinants of Intentions to Vaccinate' (DIVA©) questionnaire that aims to assess PCPs' attitudes and beliefs toward vaccination. METHODS: The DIVA questionnaire was derived from a literature review and PCPs focus groups. Scoring and early validation of the DIVA questionnaire were determined during a cross-sectional study conducted in France. During the study, PCPs had to complete the DIVA questionnaire for any of the six vaccine-preventable diseases (VPDs) to which they were randomly assigned (measles, pertussis, pneumococcus infection, seasonal influenza, human papillomavirus -HPV- infection and tetanus). Descriptive analyses of items and the analysis of the grouping of items into domains were conducted. Internal consistency reliability and construct validity was assessed according to each VPD. RESULTS: The DIVA questionnaire was completed by 1,069 PCPs and was well accepted. The 'Commitment of the PCP to the vaccination approach' score showed very good internal consistency reliability (Cronbach's alpha >0.70 overall and for each VPD). The construct validity of the DIVA questionnaire was confirmed. CONCLUSIONS: The DIVA questionnaire is a valid and reliable measure of PCPs' attitudes and beliefs toward vaccination.

Capturing patient-reported sleep disturbance in atopic dermatitis clinical trials.

BACKGROUND: Patient-focused approaches to capturing day-to-day variability in sleep disturbance are needed to properly evaluate the sleep benefits of new treatments. Such approaches rely on patient-reported outcome (PRO) measures validated in the target patient population. METHODS: Using atopic dermatitis (AD) as an example of a disease in which sleep is commonly disturbed, we developed a strategy for measuring sleep disturbance in AD trials. In developing this strategy, we conducted a targeted literature review and held concept elicitation interviews with adolescents and adults with AD. We subsequently identified potentially suitable PRO measures and cognitively debriefed them. Finally, we evaluated their psychometric properties using data from phase 2b (NCT03100344) and phase 3 (NCT03985943 and NCT03989349) clinical trials. RESULTS: The literature review confirmed that sleep disturbance is a key impact of AD but failed to identify validated PRO measures for assessing fluctuations in sleep disturbance. Subsequent concept elicitation interviews confirmed the multidimensional nature of sleep disturbance in AD and supported use of a single-item measure to assess overall sleep disturbance severity, complemented by a diary to capture individual components of sleep disturbance. The single-item sleep disturbance numerical rating scale (SD NRS) and multi-item Subject Sleep Diary (SSD)-an AD-adapted version of the Consensus Sleep Diary-were identified as potentially suitable PRO measures. Cognitive debriefing of the SD NRS and SSD demonstrated their content validity and their understandability to patients. Psychometric analyses based on AD trial data showed that the SD NRS is a well-defined, reliable, and fit-for-purpose measure of sleep disturbance in adults with AD. Furthermore, the SD NRS correlated with many SSD sleep parameters, suggesting that most concepts from the SSD can be covered using the SD NRS. CONCLUSIONS: Using these findings, we developed an approach for measuring sleep disturbance in AD trials. Subject to further research, the same approach could also be applied to future trials of other skin diseases where itch causes sleep disturbance.

Dyslipidemia in Adults with Type 2 Diabetes in a Rural Community in Ganadougou, Mali: A Cross-Sectional Study.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

Validation of the Peak Pruritus Numerical Rating Scale as a Patient-Reported Outcome Measure in Prurigo Nodularis.

INTRODUCTION: Validated patient report tools for quantifying patient experiences of itch in prurigo nodularis (PN) are limited. This study aimed to evaluate the validity of the 11-point peak pruritus numerical rating scale (PP NRS) as a single-item patient-reported outcome (PRO) measure for assessing itch severity in PN. METHODS: Content validity of the PP NRS was evaluated through qualitative interviews with adults with PN. The PP NRS was then psychometrically evaluated using data from a placebo-controlled trial of nemolizumab in adults with PN, during which patients completed the PP NRS daily. Meaningful within-patient change was estimated from the qualitative interviews and by anchor- and distribution-based analyses of trial data. RESULTS: The interview participants (N = 21) all understood the PP NRS and reported itch as their worst symptom overall. The PP NRS showed good test-retest reliability and demonstrated convergent validity and known-groups validity. PP NRS scores improved more in patients classified as "improved" on other clinical outcome measures than in those classified as "worsened/unchanged". Triangulation of the different estimates identified a 2- to 5-point decrease in PP NRS score as a meaningful within-patient change threshold. CONCLUSION: The PP NRS is a content-valid and reliable PRO measure for quantifying itch severity in adults with PN in clinical trials. TRIAL REGISTRATION NUMBER: NCT03181503.

Prurigo nodularis is a skin disease where the skin becomes inflamed and very itchy. Itching and scratching can ruin the lives of people with prurigo nodularis. For doctors to know how well treatments for prurigo nodularis are working, they need to be able measure how bad their patients' itching is. Here we tested whether a tool called the peak pruritus numeric rating scale (PP NRS) can be used to reliably measure itching in patients with prurigo nodularis. The PP NRS asks patients to rate their itch "at the worst moment during the previous 24 h" on a scale from 0 ("no itch") to 10 ("worst itch imaginable"). We interviewed 21 patients with prurigo nodularis. Overall, itch was their worst symptom. They were able to use the PP NRS with few or no problems. To further explore whether the PP NRS can be used by patients with prurigo nodularis, we also obtained data from a clinical study. In this clinical study, patients with prurigo nodularis received a drug that might one day be used to treat their disease. They completed the PP NRS daily during the time they received the drug. When we analyzed the data from the clinical study, we found that the PP NRS has the properties a tool like this needs to be useful. We also concluded that a decrease of 2­5 points on the PP NRS scale would be a meaningful improvement in itching for patients with prurigo nodularis.

The Sleep Disturbance Numerical Rating Scale: Content Validity, Psychometric Validation, and Meaningful Within-Patient Change in Prurigo Nodularis.

INTRODUCTION: Sleep is often disturbed in patients with prurigo nodularis (PN). To address the lack of validated patient-reported outcome (PRO) measures for quantifying sleep disturbance in PN, we evaluated the Sleep Disturbance Numerical Rating Scale (SD NRS) as a single-item PRO measure for quantifying sleep disturbance in PN. METHODS: Adults with PN participated in qualitative interviews, which included concept elicitation and cognitive debriefing of the SD NRS. The SD NRS was evaluated psychometrically using data from a phase 2 randomized trial in adults with PN (NCT03181503). Other PRO assessments included the Average Pruritus (AP) NRS, AP Verbal Rating Scale (VRS), peak pruritus (PP) NRS, PP VRS, and Dermatology Life Quality Index (DLQI). Reliability, validity, and responsiveness of the SD NRS were evaluated, and meaningful within-patient change was estimated from qualitative interview responses and quantitative trial data. RESULTS: All interview participants (N = 21) experienced sleep disturbance and most (95%) understood the SD NRS as intended. The SD NRS demonstrated test-retest reliability based on intra-class correlation coefficients for itch-stable participants of 0.87 for the AP VRS and 0.76 for the PP VRS. At baseline, Spearman's rank-order correlation coefficients were moderate to strong (0.3-0.8) between the SD NRS and the AP NRS, AP VRS, PP NRS, PP VRS, and DLQI. Known-groups validity was demonstrated by higher (worse) SD NRS scores in participants with worse scores on the AP NRS, AP VRS, PP VRS, and DLQI. Improvements in SD NRS scores were greater in participants classified as "improved" versus "worsened/unchanged" on the anchor PROs. A 2- to 4-point decrease on the 11-point SD NRS scale was identified as a meaningful within-patient change. CONCLUSION: The SD NRS is a well-defined, reliable, and valid PRO measure that can be used in daily practice and clinical trials to capture sleep disturbance in adults with PN.

Patients with the skin disease prurigo nodularis often sleep badly because their skin is very itchy in the evening and at night. In assessing the effectiveness of new treatments for prurigo nodularis, it is useful to know whether patients sleep better when taking them. Here, we tested whether the "Sleep Disturbance Numerical Rating Scale" (SD NRS), a tool for measuring sleep, can be used by patients with prurigo nodularis. The SD NRS asks patients to score their sleep loss during the previous night on a scale of 0 ("no sleep loss") to 10 ("I did not sleep at all"). When we interviewed 21 patients with prurigo nodularis, 19 of them had problems falling asleep and 18 of them woke up every night. Most of the patients found the SD NRS easy to use. To further explore whether the SD NRS is suitable for patients with prurigo nodularis, we also analyzed data from a European clinical study in which patients with prurigo nodularis received nemolizumab, a new treatment being developed for the disease. Patients completed the SD NRS each morning during the clinical study. We found that the SD NRS has the necessary properties to be useful for assessing sleep on a daily basis. We also determined that a 2- to 4-point decrease on the SD NRS scale would represent a meaningful improvement in sleep for patients with prurigo nodularis. We conclude that the SD NRS is a useful tool for assessing sleep in prurigo nodularis patients participating in clinical studies.

Monitoring Severity of Respiratory Syncytial Virus (RSV) in Infants and Young Children Using the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS): Results of Initial Quantitative Validation.

PURPOSE: PRESORS ClinRO completed by clinicians and ObsRO completed by caregivers were developed to characterize the clinical course of respiratory syncytial virus (RSV) infection. This study describes preliminary analysis of PRESORS' measurement properties using clinical trial data. PATIENTS AND METHODS: PRESORS ClinRO and ObsRO data were collected in a 28-day randomized, double-blind, Phase 1b trial of JNJ-53718678 or placebo in infants and children ≤24 months of age treated for RSV infection in hospitals. PRESORS data were scored and key psychometric properties of scores were evaluated, including ability to discriminate between known groups and to detect change over time. Time to resolution of RSV signs was explored using two responder definitions. RESULTS: Daily completion rates for PRESORS ClinRO and ObsRO were high for the 44 children in the study (median: 100% and 93%, respectively). Large floor effects were observed at baseline for signs of severe RSV infection that were either absent (cyanosis, fever, apnea) or rarely reported (reduced urination/dehydration, vomiting). Implausible ObsRO ratings suggested some caregivers could not accurately measure heart rate. Known-group validity was confirmed: children in poor health based on baseline ClinRO had mean baseline composite scores that were significantly worse for both ObsRO (p=0.001) and ClinRO (p<0.001) compared to those with better overall health. ObsRO (p=0.009) and ClinRO (p<0.001) composite scores were responsive to change in overall health status from baseline to Day 3. Mean scores for RSV sign dimensions decreased rapidly from baseline to Day 7 except for coughing and sleep ratings by caregivers. Time to recovery varied greatly depending on definitions used. CONCLUSION: PRESORS ClinRO and ObsRO can inform endpoints and enable monitoring the clinical course of RSV in pediatric trials. Improved alignment between ClinRO and ObsRO and revisions ensuring caregivers can assess all signs will be addressed in revised PRESORS.

Applying a mixed methods design to test saturation for qualitative data in health outcomes research.

Saturation, a core concept in qualitative research, suggests when data collection might end. It is reached when no new relevant information emerges with additional interviews. The aim of this research was to explore whether a mixed methods design could contribute to the demonstration of saturation. Firstly, saturation was conceptualized mathematically using set theory. Secondly, a conversion mixed design was conducted: a set of codes derived from qualitative interviews were quantitized and analyzed using partial least squares (PLS) regression to document whether saturation was reached. A qualitative study conducted by other researchers prior to this work (i.e. none of the present authors was involved in this study) was used to test saturation using PLS regression. This illustrative qualitative study aimed to investigate the impact of Clostridium difficile infection (CDI) on nurses' work in the hospital and the results were published elsewhere (Guillemin et al. 2015). Semi-structured interviews were conducted with 12 nurses. Saturation was characterized by the cumulative percentage of variability accounted for by PLS factors. After 12 interviews, this percentage was 51% which suggests that saturation was achieved at least on main themes. Two main themes identifying similarities in the experience of nurses caring for patients with CDI were identified: Organization/Coordination of the working day and Time-consuming work. Although dependent on the coding of qualitative data, PLS regression of quantitized data from qualitative interviews generated useful information for the determination of saturation.

New Putative Antimicrobial Candidates: In silico Design of Fish-Derived Antibacterial Peptide-Motifs.

Antimicrobial resistance remains a great threat to global health. In response to the World Health Organizations' global call for action, nature has been explored for novel and safe antimicrobial candidates. To date, fish have gained recognition as potential source of safe, broad spectrum and effective antimicrobial therapeutics. The use of computational methods to design antimicrobial candidates of industrial application has however, been lagging behind. To fill the gap and contribute to the current fish-derived antimicrobial peptide repertoire, this study used Support Vector Machines algorithm to fish out fish-antimicrobial peptide-motif candidates encrypted in 127 peptides submitted at the Antimicrobial Peptide Database (APD3), steered by their physico-chemical characteristics (i.e., positive net charge, hydrophobicity, stability, molecular weight and sequence length). The best two novel antimicrobial peptide-motifs (A15_B, A15_E) with the lowest instability index (-28.25, -22.49, respectively) and highest isoelectric point (pI) index (10.48 for each) were selected for further analysis. Their 3D structures were predicted using I-TASSER and PEP-FOLD servers while ProSA, PROCHECK, and ANOLEA were used to validate them. The models predicted by I-TASSER were found to be better than those predicted by PEP-FOLD upon validation. Two I-TASSER models with the lowest c-score of -0.10 and -0.30 for A15_B and A15_E peptide-motifs, respectively, were selected for docking against known bacterial-antimicrobial target-proteins retrieved from protein databank (PDB). Carbapenam-3-carboxylate synthase (PDB ID; 4oj8) yielded the lowest docking energy (-8.80 and -7.80 Kcal/mol) against motif A15_B and A15_E, respectively, using AutoDock VINA. Further, in addition to Carbapenam-3-carboxylate synthase, these peptides (A15_B and A15_E) were found to as well bind to membrane protein (PDB ID: 1by3) and Carbapenem synthetase (PDB: 1q15) when ClusPro and HPEPDOCK tools were used. The membrane protein yielded docking energy scores (DES): -290.094, -270.751; coefficient weight (CW): -763.6, 763.3 for A15_B and A15_E) whereas, Carbapenem synthetase (PDB: 1q15) had a DES of -236.802, -262.75 and a CW of -819.7, -829.7 for peptides A15_B and A15_E, respectively. Motif A15_B of amino acid positions 2-19 in Pleurocidin exhibited the strongest in silico antimicrobial potentials. This segment could be a good biological candidate of great application in pharmaceutical industries as an antimicrobial drug candidate.

Comparative effectiveness of avelumab versus chemotherapy in Merkel cell carcinoma: innovative use of patient insights.

AIM: To assess patient experience with chemotherapy and avelumab in metastatic Merkel cell carcinoma (mMCC). METHODS: In the JAVELIN Merkel 200 trial, chemotherapy-refractory mMCC patients could participate in optional qualitative interviews at baseline documenting recollection of previous chemotherapy experience, and at weeks 13/25 documenting current experience with avelumab. Functional Assessment of Cancer Therapy subscale for melanoma questionnaire (FACT-M) was administered in parallel. RESULTS: In our sample, chemotherapy was associated with an unpleasant experience. On selected FACT-M items addressing chemotherapy-impacted concepts, most patients receiving avelumab were improved or stable; few worsened. In addition, a few patients spontaneously reported experiencing less toxicity with avelumab than experienced during previous chemotherapy. CONCLUSION: This approach merging qualitative and quantitative data suggests that mMCC patients report a better experience with avelumab than with chemotherapy.

How to address the challenges of evaluating treatment benefits-risks in rare diseases? A convergent mixed methods approach applied within a Merkel cell carcinoma phase 2 clinical trial.

BACKGROUND: Demonstrating treatment benefits within clinical trials in the context of rare diseases is often methodologically and practically challenging. Mixed methods research offers an approach to overcome these challenges by combining quantitative and qualitative data, thus providing a better understanding of the research question. A convergent mixed methods design in the context of Merkel cell carcinoma, a rare skin cancer, was used during the JAVELIN Merkel 200 trial (NCT02155647). METHODS: Nine patients receiving avelumab in the JAVELIN Merkel 200 trial were interviewed at baseline prior to receiving study treatment, and at 13 weeks and 25 weeks after first avelumab administration. Key concepts of interest identified from the baseline interviews were physical functioning, fatigue/energy, and pain. Patient perceptions of the overall change in their cancer-related health status since starting study treatment were also recorded. During qualitative analysis, at each time-point, each concept of interest was assigned a category describing the trend in change (e.g. newly emerged, no change/stable, improved, worsened, ceased/disappeared). In parallel, patients' tumour status was determined by the clinical overall response status as per the clinical trial protocol. RESULTS: A high concordance between patient-reported qualitative data and assessed tumour response was observed. All eight patients who clinically improved had perceived a subjective improvement in their disease since the beginning of the study; the single patient whose disease worsened had a perceived deterioration. Patient perceived benefit in physical functioning, fatigue/energy and pain was subsequent to the measured change in clinical status as assessed by tumour response. This suggests that patient-reported assessment should be examined over the long term in order to optimally capture meaningful treatment effect. CONCLUSION: Embedding qualitative research in clinical trials to complement the quantitative data is an innovative approach to characterise meaningful treatment effect. This application of mixed methods research has the potential to overcome the hurdles associated with clinical outcomes assessment in rare diseases.

Relationship Between FEV1 and Patient-Reported Outcomes Changes: Results of a Meta-Analysis of Randomized Trials in Stable COPD.

Background: This meta-analysis assessed the relationship between change from baseline (CFB) in spirometric measurements (trough forced expiratory volume in 1 second [FEV1] and FEV1 area under the curve [AUC]) and patient-reported outcomes (St. George's Respiratory Questionnaire total score [SGRQ] CFB, Transition Dyspnea Index [TDI] and exacerbation rates) after 6-12 months' follow-up, using study treatment-group level data. Methods: A systematic literature search was performed for randomized controlled trials of ≥24 weeks duration in adults with chronic obstructive pulmonary disease (COPD). Studies reporting ≥1 spirometric measurement and ≥1 patient-reported outcome (PRO) at baseline and at study endpoint were selected. The relationships between PROs and spirometric endpoints were assessed using Pearson correlation coefficient and meta-regression. Results: Fifty-two studies (62,385 patients) were included. Primary weighted analysis conducted at the last assessment showed a large significant negative correlation (r, -0.68 [95% confidence interval (CI); -0.77, -0.57]) between trough FEV1 and SGRQ. Improvement of 100 mL in trough FEV1 corresponded to a 5.9 point reduction in SGRQ. Similarly, a reduction of 4 points on SGRQ corresponded to 40 mL improvement in trough FEV1 (p<0.001). The weighted correlation coefficients of trough FEV1 with TDI, exacerbation rate (all) and exacerbation rate (moderate/severe) at last assessment point were 0.57, -0.69 and -0.57, respectively (all p<0.05). For the analyses excluding placebo groups, the correlations of FEV1 with SGRQ and TDI were lower but significant. Conclusions: A strong association exists between changes in spirometric measurements and changes in PROs.

Measuring patients' satisfaction with their anti-TNF treatment in severe Crohn's disease: scoring and psychometric validation of the Satisfaction for PAtients in Crohn's diseasE Questionnaire (SPACE-Q(©)).

BACKGROUND: Severe Crohn's disease management includes anti-tumor necrosis factor (anti-TNF) drugs that differ from early-stage treatments regarding efficacy, safety, and convenience. This study aimed to finalize and psychometrically validate the Satisfaction for PAtients in Crohn's diseasE Questionnaire (SPACE-Q(©)), developed to measure satisfaction with anti-TNF treatment in patients with severe Crohn's disease. METHODS: A total of 279 patients with severe Crohn's disease receiving anti-TNF therapy completed the SPACE-Q 62-item pilot version at inclusion and 12 and 13 weeks after first anti-TNF injection. The final SPACE-Q scoring was defined using multitrait and regression analyses and clinical relevance considerations. Psychometric validation included clinical validity against Harvey-Bradshaw score, concurrent validity against Treatment Satisfaction Questionnaire for Medication (TSQM), internal consistency reliability, test-retest reliability, and responsiveness against the patient global impression of change (PGIC). RESULTS: Quality of completion was good (55%-67% of patients completed all items). Four items were removed from the questionnaire. Eleven scores were defined within the final 58-item SPACE-Q: disease control; symptoms, anal symptoms, and quality of life transition scales; tolerability; convenience; expectation confirmation toward efficacy, side effects, and convenience; satisfaction with treatment; and motivation. Scores met standards for concurrent validity (correlation between SPACE-Q satisfaction with treatment and TSQM satisfaction scores =0.59), internal consistency reliability (Cronbach's α=0.67-0.93), test-retest reliability (intraclass correlations =0.62-0.91), and responsiveness (improvement in treatment experience assessed by the SPACE-Q for patients reporting improvement on the PGIC). Significantly different mean scores were observed between groups of patients with different Harvey-Bradshaw disease severity scores. CONCLUSION: The SPACE-Q is a valid, reliable, and responsive instrument to measure satisfaction with anti-TNF treatment in patients with severe Crohn's disease and for use in future studies.