Patient-reported Outcomes Instrument For Use Research Articles

Development of a novel PRO instrument for use in familial chylomicronemia syndrome

BackgroundFamilial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by high levels of circulating triglycerides, negatively impacts multiple organs, including the liver and pancreas.ObjectiveThe objective of this study was to develop and support the content validity of a novel patient-reported outcome (PRO) measure addressing FCS symptoms and impacts. To facilitate use in clinical trials of new treatments, evidence supporting the new measure needed to be consistent with regulatory guidance and requirements.MethodsA pool of items addressing symptoms and impacts of FCS was initially developed based on data from a large burden-of-illness study with patients with FCS as well as a review of available literature and existing PRO measures. Two rounds of qualitative interviews were conducted with patients with FCS (N = 10) to refine the draft items and support the measure’s content validity. Each interview began with concept elicitation followed by cognitive debriefing of the draft FCS measure.ResultsPatient-reported symptoms and impacts of FCS were generally consistent with those identified by the burden-of-illness study; abdominal pain was particularly prevalent and salient for patients. Suggested changes to the draft item pool were generally minor. Comprehensibility and ease of completion for the final instrument were confirmed during the second set of interviews.ConclusionThe content validity of the final 17-item FCS Symptoms and Impacts Scale is strongly supported by patient input gathered through both a large burden-of-illness study and qualitative research. To further support use in clinical trials, psychometric evaluation of the measure is underway.

PSS14 Qualitative Exploration of Patient Experiences of Visual Function Impairments and Health-Related Quality of Life Impacts Associated with RLBP1 Retinitis Pigmentosa in a Sample of Canadian Patients

RLBP1 retinitis pigmentosa (RP) is a rare inherited retinal degeneration caused by biallelic mutations in the RLBP1 gene. Visual impairments associated with RP result in significant impacts on patients’ vision-dependent activities of daily living (ADL) and broader health-related quality of life (HRQoL). However, there is a paucity of research exploring the patient experience of RP in general and RLBP1 RP. The objective of this qualitative study was to explore the experience of RLBP1 RP from the patient perspective in Canada. Semi-structured qualitative concept elicitation telephone interviews were conducted with eight Canadian RLBP1 RP adult patients at a site in Newfoundland. All patients had a genetic diagnosis of RLBP1 RP. Qualitative thematic analysis of verbatim interview transcripts was performed. Findings contributed to refinement of a conceptual model of RP detailing relevant visual function symptom and impact measurement concepts. All eight RLBP1 RP patients (33-70 years) reported experiencing night blindness, reduced peripheral vision, difficulty seeing in very bright lighting and difficulty adapting to new lighting conditions. Visual function symptoms led to proximal vision-dependent impacts on mobility and ADLs. Visual aids commonly used included sunglasses, white cane and assistive devices. Impacts on broader HRQoL domains included social functioning, emotional well-being, work/school functioning and financial. Visual functioning and impacts on vision-dependent activities were moderated by lighting conditions and familiarity of environment. Findings from this study provide in-depth insights into the visual function symptoms and impacts on vision-dependent ADLs and broader HRQoL experienced by RLBP1 RP patients. Results are consistent with evidence generated in other RP genotypes and suggest that the experience of RP is similar across different mutations, such as RPE65 and RPGR. Interview findings supported the development of a RP specific patient-reported outcome instrument for use in clinical trials and to track disease severity in future clinical practice.

Health-Related Quality of Life in Focal Segmental Glomerular Sclerosis and Minimal Change Disease: A Qualitative Study of Children and Adults to Inform Patient-Reported Outcomes

Rationale & ObjectiveAssessment of how patients feel and function is needed for clinical care and research for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). The objective of this study was to develop a patient-reported outcome assessment appropriate for use in children and adults with FSGS and MCD.Study DesignQualitative study using semi-structured interviews.Setting & Participants48 semi-structured interviews with children aged 8 to 17 years (n = 11) and adults (n = 10) with FSGS and children aged 8 to 17 (n = 11) and adults (n = 16) with MCD recruited from 3 academic medical centers.Analytical ApproachLatent content analysis.ResultsFSGS and MCD have a pervasive and comparable impact on physical, social, and mental health-related quality of life regardless of age or diagnosis. Physical symptoms of swelling, fatigue, and pain were articulated by most participants. Disease management was also a frequent topic of discussion; participants described their experiences with medication and associated side effects, as well as lifestyle changes made to manage their disease (ie, dietary changes and frequent medical appointments). These discussions often identified a profound impact on physical abilities and life participation. In many instances, participants described the negative impact these symptoms had on their mood and sense of self, with most participants reporting feelings of anxiety.LimitationsParticipants were primarily non-Hispanic White and English speaking, which may limit generalizability.ConclusionsOur results suggest that there are commonalities to the FSGS-MCD patient experience of health-related quality of life that will enable the generation of a disease-specific FSGS-MCD patient-reported outcomes instrument for use in children and adults. The development of this tool is intended to facilitate better care and support clinical research for these individuals.

Patient experiences with hypertrophic cardiomyopathy: a conceptual model of symptoms and impacts on quality of life

BackgroundHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder defined by left ventricular hypertrophy that cannot be explained by another cardiac or systemic disease. There is a general lack of knowledge about patients’ perspectives on the symptoms and day-to-day limitations they experience as a result of HCM. We therefore sought an in-depth understanding of patients’ experiences of obstructive (oHCM) and nonobstructive (nHCM) forms of the disease, including symptoms and their quality of life impacts, and to develop a conceptual model to capture them.MethodsDevelopment of the HCM conceptual model involved a web-based survey to capture patients’ insights, a targeted literature review (which included relevant guidelines and patient advocacy websites), one-to-one interviews with clinical experts, and one-to-one qualitative concept elicitation interviews with patients. Key symptoms and their impacts most important to patients’ experiences were identified and used to develop a conceptual model of the patient experience with HCM.ResultsThe HCM symptoms reported by patient interviewees (n = 27) were largely consistent with findings from the patient web survey (n = 444), literature review, and interviews with three expert clinicians. The symptoms most commonly reported in patient interviews included tiredness (89%), shortness of breath (89%), shortness of breath with physical activity (89%), and dizziness/light-headedness (89%). Other symptoms commonly reported included chest pain (angina) (70%), chest pain (angina) with physical exertion (70%), and palpitations (fluttering or rapid heartbeat) (81%). The most commonly reported impacts of HCM symptoms on patients’ lives included limitations to physical activities (78%), emotional impacts, including feeling anxious or depressed (78%), and impacts on work (63%). Symptoms and impacts were similar for both oHCM and nHCM.ConclusionsA conceptual model was developed, which identifies the core symptoms that patients with oHCM and nHCM reported as most frequent and most important: shortness of breath, palpitations, fatigue/tiredness, dizziness/light-headedness, and chest pain, as well as the impacts those symptoms have on patients’ lives. This HCM conceptual model reflecting patients’ experiences and perspectives was used in the development of a patient-reported outcomes instrument for use in clinical trials and it may also help inform the clinical management of HCM.

Qualitative patient interviews on symptoms and impacts in metastatic synovial sarcoma (mSS).

e23576 Background: Synovial sarcoma (SS), a soft tissue sarcoma, is a rare and aggressive malignancy, with significant morbidity and mortality associated with mSS. There are currently no patient-reported outcome (PRO) instruments specific to mSS patients and little qualitative research to understand impacts on mSS patients’ health-related quality of life (QoL). The objective of this study was to characterize the symptoms and impacts experienced by mSS patients to inform the selection of content-valid PRO instruments for use in investigational trials in mSS patients. Methods: This was a non-interventional, qualitative interview study of adult participants in the United States (US) with physician-confirmed mSS. Participants were consented from a large private practice in the US. Six semistructured concept elicitation interviews (60–90m by telephone) were conducted by trained interviewers. Participants were asked to describe their mSS symptoms and their impact on functioning in an open-ended fashion with follow-up probes. Verbatim transcripts were analyzed using thematic analysis methods and Atlas.Ti software. Socio-demographics and clinical characteristics were collected by the site. The study received Institutional Review Board (IRB) approval from Western IRB. Results: Among the 6 participants, average age was 45y (range 21–61y) and 2 were female. All 6 participants had pulmonary metastasis, 1 participant had a liver metastasis, and 1 participant had a mediastinal mass. The most common symptoms participants spontaneously identified were pain (n = 6), fatigue (n = 6), coughing (n = 5, with 2 upon probing), shortness of breath (n = 4), phlegm/mucus in the lungs (n = 3), coughing up blood (n = 2), and gastrointestinal complications (n = 2). Nerve/shooting/burning pain (n = 5) was mentioned upon probing. Participants also reported impacts of their disease on sleep (quantity and quality) (n = 6), physical activity (n = 6), social life (n = 6), daily activities (n = 5), emotions (n = 5), loss of appetite (n = 3), and finances (n = 1). Although not spontaneously reported, global ratings of overall health and QoL were considered relevant by all participants. Conclusions: This is the first study to identify patient-relevant symptoms and impacts associated with mSS. Further interviews with additional participants are ongoing, and we will analyze these data to identify appropriate PRO instruments for use in investigational trials in mSS patients. Funding: GlaxoSmithKline (209386).

PRO95 PSYCHOMETRIC EVALUATION OF A PATIENT-REPORTED OUTCOMES (PRO) INSTRUMENT FOR CONGENITAL THROMBOTIC THROMBOCYTOPENIC PURPURA (CTTP)

Congenital thrombotic thrombocytopenic purpura (cTTP, hereditary cTTP) is an ultra-rare, life-threatening disorder where patients experience substantial comorbidity and decreased health-related quality of life (HRQoL). Baxalta (a Takeda company) developed a cTTP-specific patient-reported outcome (PRO) instrument and confirmed its content validity using qualitative cognitive debriefing. This study evaluated the psychometric properties of a newly developed cTTP-specific PRO instrument. This US/UK observational study (NCT03519672) was conducted from July 2018-April 2019 in patients aged ≥18 years receiving treatment for cTTP. Patients were enrolled through investigator sites and direct-to-patient recruitment. Patients completed self-administered PRO measures electronically at baseline and day 14. The cTTP-specific instrument assessed symptoms and impact of cTTP and consists of 5 multiple-item domains (pain/bruising, cognitive impairment, visual impairment, mood, treatment burden) and 3 single-item domains (fatigue, headaches, activity limitation). Convergent and divergent validity were determined by assessing the relationship between cTTP-specific PRO domains and domains of 8 additional PROs using Spearman rank correlation coefficients. Known-groups validity was assessed by comparing two patient-reported impression of severity (PGI-S) groups using t-tests. Internal reliability was assessed using Cronbach’s alpha. Test–retest reliability was assessed using intraclass correlation coefficients (ICC) between the two timepoints. In the 36 patients evaluated, high-to-moderate correlations (r≥0.4) were observed for 10 of 13 pairs of domains and/or total scores, confirming convergent validity. Low correlations (r<0.3) were observed for 7 of 10 hypothesized relationships, confirming divergent validity. Differences in mean cTTP scores between the two PGI-S groups were significant (p≤0.05) for all domains/most items, confirming known-groups validity. Internal Consistency was confirmed with high Cronbach’s alpha (baseline, 0.88; day 14, 0.91). Test-retest reliability was confirmed with a high ICC (0.96). This study provided evidence for the psychometric properties of the newly developed cTTP-specific PRO instrument for use in research and clinical practice to assess HRQoL among cTTP patients.

Fatigue numeric rating scale validity, discrimination and responder definition in patients with psoriatic arthritis

ObjectivesThis study assessed the psychometric properties of the fatigue numeric rating scale (NRS) and sought to establish values for clinically meaningful change (responder definition).MethodsUsing disease-specific clinician-reported and patient-reported data from...

Development of a Patient-Reported Outcome Instrument for Patients With Severe Lower Extremity Trauma (LIMB-Q): Protocol for a Multiphase Mixed Methods Study.

BackgroundA current limitation in the care of patients with severe lower extremity traumatic injuries is the lack of a rigorously developed patient-reported outcome (PRO) instrument specific to lower extremity trauma patients.ObjectiveThis mixed methods protocol aims to describe phases I and II of the development of a PRO instrument for lower extremity trauma patients, following international PRO development guidelines.MethodsThe phase I study follows an interpretive description approach. Development of the PRO instrument begins with identifying the concepts that are important to patients, after which a preliminary conceptual framework is devised from a systematic literature review and used to generate an interview guide. Patients aged 18 years or above with limb-threatening lower extremity traumatic injuries resulting in reconstruction, amputation, or amputation after failed reconstruction will be recruited. The subjects will participate in semistructured, in-depth qualitative interviews to identify all important concepts of interest. The qualitative interview data will be coded with top-level domains, themes, and subthemes. The codes will then be utilized to refine the conceptual framework and generate preliminary items and a set of scales. The preliminary scales will be further refined via a process of conducting cognitive debriefing interviews with lower extremity trauma patients and soliciting expert opinions. Phase III will include a large-scale field test, using Rasch measurement theory to analyze the psychometric properties of the instrument; shortening and finalizing the scales; and determining the reliability, validity, and responsiveness of the instrument.ResultsPhases I and II of this study have been funded. Phase I of this study has been completed, and phase II began in January 2019 and is expected to be completed in November 2019. Phase III will begin following the completion of phase II.ConclusionsThis protocol describes the initial phases of development of a novel PRO instrument for use in lower extremity trauma patients.International Registered Report Identifier (IRRID)DERR1-10.2196/14397

Assessing Patient-Reported Outcomes in People with Myelodysplastic Syndromes: Can a Customized Selection of Items from the EORTC Library Enhance the EORTC QLQ-C30?

INTRODUCTIONAssessing patient-reported outcomes (PROs) is an essential part of understanding the ways in which a new drug might affect how a patient with cancer feels and functions within a clinical trial. Certain widely used PRO measures are now being supplemented with a selection of items from available item banks to ensure the measure is targeted to the specific context of use. Previous mixed methods research in higher risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML), and low blast acute myeloid leukemia (LB AML) led to the development of a conceptual model of the symptoms and impacts for this population. It informed a PRO measurement strategy based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) along with an additional, customized selection of 10 supplemental items from the EORTC library to cover unaddressed concepts. Clinical features such as anemia cause fatigue and dyspnea, which may negatively impact patient functioning, thus further emphasizing the importance of the patient voice when evaluating the value of a new therapy to patients. The purpose of this research was to incorporate the patient voice and generate information on this measurement strategy in a sample of people with HR MDS/ CMML and LB AML.METHODSThis study was a one-time, cross-sectional patient-reported survey administered online. People living with HR MDS, non-proliferative CMML, and LB AML were recruited through the MDS Foundation, social media, and recruitment agencies. Patients completed the EORTC QLQ-C30 plus 10 supplemental items from the EORTC item library. In addition to PRO data, they were also asked to record demographics and disease-related information. Responses to the 40 PRO items were described and psychometric analyses based on Rasch measurement theory (RMT) were conducted on the original multi-item domains of the EORTC QLQ-C30. RMT analysis defines how a set of items should perform to generate reliable and valid measurements, which is important for the generalizability of the PRO instrument's psychometric evaluations to other contexts of use. RMT analyses were also performed on the following, enhanced domain measures which included original items and supplemental items: fatigue, dyspnea, physical functioning, and role functioning.RESULTSA total of 51 patients were recruited and participated in the online survey (HR MDS: 51%; CMML: 27%; LB AML: 10%). The mean age was 67.2 (SD: 11.8) and 49% of patients were female. The description of responses showed a possible floor effect for several EORTC QLQ-C30 items (i.e. a substantial percentage of responder reported the lowest value of the scale), whereas the responses to the supplemental items were well distributed across the response categories (Figure). This confirmed that the customized supplemental item selection was well targeted to the patient sample. Overall, the RMT psychometric examination of the original EORTC QLQ-C30 domain scores showed satisfactory ability to assess key outcomes for people with HR MDS/CMML and LB AML including fatigue and physical functioning. However, it highlighted some areas for possible improvement, due to gaps in the conceptual coverage of symptoms and impacts of HR MDS/CMML and LB AML. The enhanced fatigue, physical functioning and dyspnea measures that combined the original QLQ-C30 items with the supplemental items from the EORTC library showed improved measurement performances for these key domains for people with HR MDS/CMML and LB AML, typically in terms of conceptual coverage.CONCLUSIONSOur data shows how incorporating the patient voice early on in PRO measurement selection and a conceptually-driven approach to the development of customized item sets can lead to more fit-for-purpose PRO measures to be used in the context of clinical trials of patients with cancer. Specifically, while the QLQ-C30 may be a satisfactory PRO instrument for use in people with hematological stem cell disorders, it can be made more targeted and disease-specific by carefully utilizing mixed methods and selecting supplemental items from the EORTC item library. This patient-reported online survey provides early evidence, in a small sample of patients, on the appropriateness of both the original QLQ-C30 and enhanced item sets to assess PROs in HR MDS/CMML, and AML and should be further analyzed in future research. DisclosuresBell:Takeda Pharmaceuticals: Employment, Equity Ownership. Pompilus:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Christian:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Mazerolle:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Scipione:Takeda Pharmaceuticals: Employment. Bejar:Takeda: Research Funding; Celgene: Consultancy, Honoraria; Foundation Medicine: Consultancy; Modus Outcomes: Consultancy; Genoptix: Consultancy; AbbVie/Genentech: Consultancy, Honoraria; Astex/Otsuka: Consultancy, Honoraria. Galaznik:Takeda Pharmaceuticals International Co.: Employment. Fram:Takeda Pharmaceuticals: Consultancy; BeyondSpring Pharmaceuticals, Inc.: Consultancy. Faller:Takeda Pharmaceuticals: Employment, Equity Ownership. Cano:Modus Outcomes: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Research Funding. Regnault:Modus Outcomes: Employment, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Research Funding.

Psychometric Validation of the BODY-Q in Danish Patients Undergoing Weight Loss and Body Contouring Surgery.

A well-developed patient-reported outcome instrument is needed for use in Danish bariatric and body contouring patients. The BODY-Q is designed to measure changes in important patient outcomes over the entire patient journey, from obesity to post-body contouring surgery. The current study aims to psychometrically validate the BODY-Q for use in Danish patients. The process consisted of 3 stages: translation and linguistic validation, field-test, and data analysis. The translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research and World Health Organization guidelines, and field-test data were collected in 4 departments in 2 different hospitals. Field-test data were analyzed using Rasch Measurement Theory. A total of 495 patients completed the Danish BODY-Q field-test 1-4 times, leading to a total of 681 assessments with an overall response rate at 76%. Cronbach α values were ≥ 0.90, and person separation index values were in general high. The Rasch Measurement Theory analysis provided broad support for the reliability and validity of the Danish version of the BODY-Q scales. Item fit was outside the criteria for 34 of 138 items, and of these, 21 had a significant chi-square P value after Bonferroni adjustment. Most items (128 of 138) had ordered thresholds, indicating that response options worked as intended. The Danish version of the BODY-Q is a reliable and valid patient-reported outcome instrument for use in Danish bariatric and body contouring patients.

A Systematic Review of the Psychometric Properties of Patient-Reported Outcome Instruments for Use in Patients With Rotator Cuff Disease

Background: Many patient-reported outcome instruments (or questionnaires) have been developed for use in patients with rotator cuff disease. Before an instrument is implemented, its psychometric properties should be carefully assessed, and the methodological quality of papers that investigate a psychometric component of an instrument must be carefully evaluated. Together, the psychometric evidence and the methodological quality can then be used to arrive at an estimate of an instrument’s quality. Purpose: To identify patient-reported outcome instruments used in patients with rotator cuff disease and to critically appraise and summarize their psychometric properties to guide researchers and clinicians in using high-quality patient-reported outcome instruments in this population. Study Design: Systematic review. Methods: Systematic literature searches were performed to find English-language articles concerning the development or evaluation of a psychometric property of a patient-reported outcome instrument for use in patients with rotator cuff disease. Methodological quality and psychometric evidence were critically appraised and summarized through 2 standardized sets of criteria. Results: A total of 1881 articles evaluating 39 instruments were found per the search strategy, of which 73 articles evaluating 16 instruments were included in this study. The Constant-Murley score, the DASH (Disability of the Arm, Shoulder, and Hand), and the Shoulder Pain and Disability Index were the 3 most frequently evaluated instruments. In contrast, the psychometric properties of the Korean Shoulder Scoring System, Shoulder Activity Level, Subjective Shoulder Value, and Western Ontario Osteoarthritis Shoulder index were evaluated by only 1 study each. The Western Ontario Rotator Cuff Index was found to have the best overall quality of psychometric properties per the established criteria, with positive evidence found in internal consistency, reliability, content validity, hypothesis testing, and responsiveness. The DASH, Shoulder Pain and Disability Index, and Simple Shoulder Test had good evidence in support of internal consistency, reliability, structural validity, hypothesis testing, and responsiveness. Inadequate methodological quality was found across many studies, particularly in internal consistency, reliability, measurement error, hypothesis testing, and responsiveness. Conclusion: More high-quality methodological studies should be performed to assess the properties in all identified instruments.

Cross-cultural adaptation to Swedish and validation of the Copenhagen Hip and Groin Outcome Score (HAGOS) for pain, symptoms and physical function in patients with hip and groin disability due to femoro-acetabular impingement

There is a lack of standardised outcome measures in Swedish for active, young and middle-aged patients with hip and groin disability. The purpose of this study was to adapt the Danish version of the Copenhagen Hip and Groin Outcome Score (HAGOS) patient-reported outcome instrument for use in Swedish patients and evaluate the adaptation according to the Consensus-Based Standards for the Selection of Health Status Measurement Instruments checklist. Cross-cultural adaptation was performed in several steps, including translation, back-translation, expert review and pretesting. The final version was evaluated for reliability, validity and responsiveness. Five hundred and two patients (337 men and 167 women, mean age 37, range 15-75) were included in the study. Cronbach's alpha for the six HAGOS-S subscales ranged from 0.77 to 0.89. Significant correlations were obtained with the international Hip Outcome Tool average score (r s = 0.37-0.68; p < 0.01) and a standardised instrument, the EuroQol, EQ-5D total score (r s = 0.40-0.60, p = 0.01), for use as a measurement of health outcome. Test-retest reliability (intraclass correlation coefficient) ranged from 0.81 to 0.87 for the six HAGOS-S subscales. The smallest detectable change ranged from 7.8 to 16.1 at individual level and 1.6-3.2 at group level. Factor analysis revealed that the six HAGOS-S subscales had one strong factor per subscale. Effect sizes were generally medium or large. The Swedish version of the HAGOS is a valid, reliable and responsive instrument that can be used both for research and in the clinical setting at individual and group level.

A standardised outcome measure of pain, symptoms and physical function in patients with hip and groin disability due to femoro-acetabular impingement: cross-cultural adaptation and validation of the international Hip Outcome Tool (iHOT12) in Swedish

There is a lack of standardised outcome measures in Swedish for active, young and middle-aged patients with hip and groin disability. The purpose of this study was to adapt the English version of the international Hip Outcome Tool (iHOT12) patient-reported outcome instrument for use in Swedish patients and evaluate the adaptation according to the consensus-based standards for the selection of health status measurement instruments checklist. Cross-cultural adaptation was performed in several steps, including translation, back-translation, expert review and pre-testing. The final version was evaluated for reliability, validity and responsiveness in a clinical study of patients [median age 37 (range 15-75)], undergoing surgery for femoro-acetabular impingement. Cronbach's alpha was 0.89, and significant correlations were obtained with the Copenhagen Hip and Groin Outcome Score (Spearman's r 0.10-0.70; p < 0.05) and the EuroQol, EQ-5D average score (Spearman's r 0.27-0.56; p < 0.01). Test-retest reliability (intraclass correlation coefficient) ranged from 0.59 to 0.93 for the individual items. The smallest detectable change ranged from 17.1 to 44.9 at individual level and 3.6 to 9.4 at group level. Factor analysis revealed one factor of pain and symptoms and another factor of physical function. Effect sizes were generally medium or large. The Swedish version of the iHOT12 is a valid, reliable and responsive instrument that can be used both for research and in the clinical setting.

Statistical challenges in drug approval trials that use patient-reported outcomes

This article describes challenging aspects of the use of patient-reported outcome instruments in clinical trials for drug approval, in our perspective as statistical reviewers at the US Food and Drug Administration. We discuss aspects of planning and interpreting results in clinical trials (1) adapting an existing patient-reported outcome instrument for use in clinical trials, (2) using multi-item patient-reported outcomes and (3) missing patient-reported outcome values from many subjects over time. These challenges are illustrated with multiple examples from different clinical trials for different indications. We finally discuss important considerations in labeling.

Introduction to the International Cartilage Repair Society Recommendation Papers.

The International Cartilage Repair Society (ICRS) has taken a leadership role in analyzing the current state of scientific development in order to provide recommendations, where possible, for clinical and preclinical studies in cartilage repair, as well as in assessments of patient-reported and tissue structural outcome measures. The result of this initiative is the publication in this volume of Cartilage of 4 recommendation papers and 1 additional recommendation paper in the January issue of 2011: Trattnig S, Winalski CS, Marlovits S, Jurvelin JS, Welsch GH, Potter HG. Magnetic resonance imaging of cartilage repair: a review. Cartilage. 2011;2:5-26. Mithoefer K, Saris DBF, Farr J, Kon E, Zaslav K, Cole B, Ranstam J, Yao J, Shive MS, Brittberg M. Guidelines for the design and conduct of clinical studies in knee articular cartilage repair: International Cartilage Repair Society recommendations based on current scientific evidence and standards of clinical care. Cartilage. 2011;2: 100-121. Roos EM, Engelhart L, Ranstam J, Anderson AF, Irrgang JJ, Marx R, Tegner Y, Davis AM. Patient-reported outcome instruments for use in patients with articular cartilage defects. Cartilage. 2011;2:122-136. Hurtig M, Buschmann MD, Fortier L, Hoemann CD, Hunziker EB, Jurvelin JS, Mainil-Varlet P, McIlwraith W, Sah RL, Whiteside RA. Preclinical studies for cartilage repair: recommendations from the International Cartilage Repair Society. Cartilage. 2011;2:137-153. Hoemann CD, Kandel R, Roberts S, Saris D, Creemers L, Manil-Varlet P, Methot S, Hollander A, Buschmann MD. Recommended guidelines for histological endpoints for cartilage repair studies in animal models and clinical trials. Cartilage. 2011;2:154-173. This series of publications addresses overall considerations in the design and execution of clinical studies (Mithoefer et al.) and preclinical studies (Hurtig et al.) as well as analyses and recommendations for patient-reported outcome measures of clinical benefit (Roos et al.) and structural histological (Hoemann et al.) and MRI (Trattnig et al.) methods available to evaluate the quality and quantity of repair tissue. Taken together, these documents represent an important accomplishment of the ICRS in regrouping its members to producing leading position papers that provide a basis for future progress in our field. These 5 publications represent consensus documents and recommendations of the ICRS. The authors were invited to participate by the ICRS board. The review process included the peer review process of the journal as well as an additional review by the ICRS board to ensure that a general consensus of the society was achieved. We believe that the readers of Cartilage will find these expert analyses and recommendations useful in their research for improved methods and products for cartilage repair. We hope that all involved benefit from this unique effort, and we truly hope that patients, payers, practitioners, and policy makers all use these documents to the benefit of the field of cartilage repair. On behalf of the ICRS board and the Cartilage editorial board,

ICRS Recommendation Document: Patient-Reported Outcome Instruments for Use in Patients with Articular Cartilage Defects.

Objective:The purpose of this article is to describe and recommend patient-reported outcome instruments for use in patients with articular cartilage lesions undergoing cartilage repair interventions.Methods:Nonsystematic literature search identifying measures addressing pain and function evaluated for validity and psychometric properties in patients with articular cartilage lesions.Results:The knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic requirements for reliability, validity, and responsiveness in cartilage repair patients. A major difference between them is that the former results in a single score and the latter results in 5 subscores. A single score is preferred for simplicity’s sake, whereas subscores allow for evaluation of separate constructs at all levels according to the International Classification of Functioning.Conclusions:Because there is no obvious superiority of either instrument at this time, both outcome measures are recommended for use in cartilage repair. Rescaling of the Lysholm Scoring Scale has been suggested, and confirmatory longitudinal studies are needed prior to recommending this scale for use in cartilage repair. Inclusion of a generic measure is feasible in cartilage repair studies and allows analysis of health-related quality of life and health economic outcomes. The Marx or Tegner Activity Rating Scales are feasible and have been evaluated in patients with knee injuries. However, activity measures require age and sex adjustment, and data are lacking in people with cartilage repair.