Outcome Assessment In Clinical Trials Research Articles

Digital health technologies to strengthen patient-centred outcome assessment in clinical trials in inflammatory arthritis.

Common to all inflammatory arthritides, namely rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis, is a potential for reduced mobility that manifests through joint pain, swelling, stiffness, and ultimately joint damage. Across these conditions, consensus has been reached on the need to capture outcomes related to mobility, such as functional capacity and physical activity, as core domains in randomised controlled trials. Existing endpoints within these core domains rely wholly on self-reported questionnaires that capture patients' perceptions of their symptoms and activities. These questionnaires are subjective, inherently vulnerable to recall bias, and do not capture the granularity of fluctuations over time. Several early adopters have integrated sensor-based digital health technology (DHT)-derived endpoints to measure physical function and activity in randomised controlled trials for conditions including Parkinson's disease, Duchenne's muscular dystrophy, chronic obstructive pulmonary disease, and heart failure. Despite these applications, there have been no sensor-based DHT-derived endpoints in clinical trials recruiting patients with inflammatory arthritis. Borrowing from case studies across medicine, we outline the opportunities and challenges in developing novel sensor-based DHT-derived endpoints that capture the symptoms and disease manifestations most relevant to patients with inflammatory arthritis.

Adaptation and Modification of Digital Cognitive Assessments for Smartphone‐based and Unsupervised Conduct

AbstractBackgroundRemote and decentralized approaches to clinical outcome assessments in clinical trials can reduce patient and trial burden, improve recruitment and retention, and lower barriers to trial participation. Remote assessment may be facilitated through smartphone‐based cognitive assessment, especially in Bring‐Your‐Own‐Device (BYOD) trials, and can also enable novel designs, for example, the use of high frequency ‘burst’ assessments. Application of such digital assessments in remote or unsupervised settings requires understanding of potential error from test administration and delivery platform (e.g., smartphones vs. computer).MethodA series of studies explored the modification of the well‐validated Cogstate Brief Battery (CBB) to include practice trials with dynamic feedback to support unsupervised cognitive assessment, and adaptations for smartphone delivery. Data were drawn from healthy populations in (1) the Healthy Brain Project, where middle‐aged adults (n = 1,594) completed unsupervised cognitive assessments on a computer, (2) a pilot study of young adults (n = 60) who completed both smartphone and computer administration, and (3) a large (n = 35,000) study of adults who completed unsupervised smartphone‐based cognitive assessments in a BYOD context.ResultData from middle‐aged adults enrolled in the Healthy Brain Project indicated that adaptation of the CBB for unsupervised computer‐based assessment had high levels of acceptability (98% complete data) and usability (95%), with data meeting criteria for low error rates and ease of understanding). In young adults, rates of test completion were high and comparable (>98%), and performance accuracy (d’s <0.2) was equivalent between smartphone and computer administration. Performance was systematically slower (d’s >0.4) on smartphone than computer. Smartphone usability was high (e.g., >85% found text and button size to be ‘just right’), but there was not a strong preference for smartphone versus computer (56% preferred smartphone) and different issues of fatigue, distraction, and use of keyboard input were raised for the platforms. Similar findings of outcome consistency across platform were observed in the large BYOD sample (N>35,000).ConclusionThese results indicate that smartphone assessment has high acceptability, good reliability, and that accuracy of performance is equivalent between smartphone and computer versions. The data also raise important issues for the successful adaptation and modification of cognitive tasks for smartphone administration.

TIPS-15 NEUROCOGNITIVE FUNCTION AND NEUROCOGNITIVE CONCERNS IN AN ONGOING PHASE III TRIAL OF PRE-OPERATIVE SRS VERSUS POST-OPERATIVE SRS FOR BRAIN METASTASES

Abstract In our ongoing phase III randomized trial (NCT03741673) evaluating risk of leptomeningeal disease (LMD) in patients with brain metastasis, patients are stratified by tumor size, location, and histology, and randomized to pre-operative SRS versus post-operative SRS. The primary endpoint is 1-year LMD-free rate, and exploratory endpoints include neurocognitive function (NCF). NCF is assessed prior to treatment and longitudinally (1.5, 6, and 12 months from the start of treatment) with the HVLT-R, TMT, and COWA yielding the Clinical Trial Battery Composite score (CTB COMP). Patients also complete the MDASI-BT, which includes a Cognitive Factor measuring patient reported cognitive concerns. Currently, 41 patients completed pre-treatment NCF baseline. Characteristics of patients with pre-treatment NCF baseline include mean (SD): age 60.0+/-11.7 years, 2.6+/-2.2 metastases, 15.2+/-10.1 cc brain metastases volume, median KPS 90 (range: 70-100), 83% white, 52% male, and 50% received AEDs at time of surgery. The most common primary cancers among this cohort were: 31% NSCLC, 19% RCC, 14% melanoma, 7% breast, 2% thyroid, and 26% other. Mean (SD) NCF z-scores ranged from z= -0.09 (1.08) to -3.09 (6.13), CTB COMP z=-1.13 (1.65), and the mean (SD) MDASI-BT Cognitive Factor score was 1.1 (1.3). Using multivariable linear regression including CTB COMP, MDASI-BT Cognitive and Affective Factor, KPS, number of and intracranial volume of metastases, only intracranial volume of metastases was statistically significantly associated with CTB COMP (B=-.058, p=.034) and only the MDASI-BT Affective Factor was statistically significantly associated with the MDASI-BT Cognitive Factor (B=.305, p=<.001). At baseline, disease factors such as tumor burden appear to be the primary driver of objectively measured neurocognitive dysfunction and mood factors appear to be the primary driver of subjective patient reported neurocognitive concerns. This has important implications for interpretation of these different clinical outcome assessments in clinical trials measuring objective neurocognitive function and subjective neurocognitive concerns.

Updated Recommendations on Evidence Needed to Support Measurement Comparability Among Modes of Data Collection for Patient-Reported Outcome Measures: A Good Practices Report of an ISPOR Task Force

The ISPOR Task Force on measurement comparability between modes of data collection for patient-reported outcome measures (PROMs) has updated the good practice recommendations from the 2009 ISPOR electronic patient-reported outcome and 2014 patient-reported outcome mixed modes Good Research Practices Task Force reports in light of accumulated evidence of measurement comparability among different modes of PROM data collection. Furthermore, with the increasing use of electronic formats of clinical outcome assessments in clinical trials and the US Food and Drug Administration’s encouragement of electronic data collection, this new task force report provides stakeholders with best practice recommendations reflecting the current body of evidence and enables them to respond to future developments in research and technology.This task force recommends an evidence-based approach to determine whether new research is needed to evaluate measurement comparability for a given questionnaire or technology. The suitability of existing evidence depends upon whether it satisfactorily demonstrates that the change in data collection mode has not affected the PROM’s measurement properties. In cases where sufficient evidence of measurement comparability exists and best practices for faithful migration are followed, this task force concludes that further testing of measurement comparability among the data collection modes is unnecessary, including cases of “mixing modes” within clinical trials such as bring your own device designs.

Measuring Psychosis: A Review of Widely Used Clinical Outcome Assessments in Clinical Trials

Accurate diagnosis and assessment of symptoms is essential to the appropriate treatment and management of individuals with psychotic disorders. It also plays a pivotal role in research, ensuring that enrolled subjects meet study-specific inclusion requirements and that their progress is accurately tracked throughout the study. Clinical outcome assessments are standardized instruments designed specifically to measure symptoms and their impact on a patient’s life and functioning. These instruments can be used to diagnose, categorize, and track symptom severity, and to measure the functional impact of disease on a patient’s quality of life. Clinical outcome assessments play a pivotal role in advancing our understanding and treatment of schizophrenia and other psychotic disorders, providing the ability to evaluate the safety and efficacy of emerging treatments and interventions. In this review article we provide an overview of the most widely used clinical outcome assessments in schizophrenia and other psychotic disorders research with a focus on clinical trials, and delve into the specific instruments commonly used to diagnose, measure symptom severity, and assess cognitive ability. A brief description of each instrument and its role in clinical outcome assessment is provided, along with advantages and limitations in implementation. Additionally, the clinician’s perspective on the administration and scoring of these scales is included, where relevant. The goal is to familiarize new clinicians and researchers with the available assessment tools, highlighting the advantages, limitations, and any other relevant information that can aid in the selection of the appropriate measurement tools for their patients and studies. Finally, we briefly discuss our view on the future of clinical outcome assessments in schizophrenia and other psychotic disorders research and clinical trials

Recommendations for the Electronic Migration and Implementation of Clinician-Reported Outcome Assessments in Clinical Trials

ObjectivesAlthough best practices from electronic patient-reported outcome (PRO) measures are transferable, the migration of clinician-reported outcome (ClinRO) assessments to electronic modes requires recommendations that address their unique properties, such as the user (eg, clinician), and complexity associated with programming of clinical content. Faithful migration remains essential to ensuring that the content and psychometric properties of the original scale (ie, validated reference) are preserved, such that clinicians completing the ClinRO assessments interpret and respond to the items the same way regardless of data collection mode. The authors present a framework for how to “faithfully” migrate electronic ClinRO assessments for successful deployment in clinical trials. MethodsCritical Path Institute’s Electronic PRO Consortium and PRO Consortium convened a consensus panel of representatives from member firms to develop recommendations for electronic migration and implementation of ClinRO assessments in clinical trials based on industry standards, regulatory guidelines where available, and relevant literature. The recommendations were reviewed and approved by all member firms from both consortia. Consensus RecommendationsStandard, minimal electronic modifications for ClinRO assessments are described. This article also outlines implementation steps, including planning, startup, electronic clinical outcome assessment system development, training, and deployment. The consensus panel proposes that functional clinical testing by a clinician or clinical outcome assessment expert, as well as copyright holder review of screenshots (if possible) are sufficient to support minimal modifications during migration. Additional evidence generation is proposed for modifications that deviate significantly from the validated reference.

The state of the art-psoriatic arthritis outcome assessment in clinical trials and daily practice.

Psoriatic arthritis is a heterogeneous condition with substantial challenges in optimising outcome measures for both clinical trials and daily practice. As with other inflammatory arthritides, there is no gold standard instrument for measuring disease activity or impact, both of which are key to evaluate therapeutic approaches in trials and monitor disease in daily practice. A wide range of domains have been highlighted in the Outcome Measures in Rheumatology (OMERACT) core domain set for psoriatic arthritis; reflecting the disease involvement in multiple tissues (joints, tendons, skin, and spine) and the heterogenous impact of the disease on individuals. This Review summarises the current evidence around outcome measure selection, considering factors such as unidimensional versus multidimensional outcomes, continuous versus binary measures, and the feasibility of these approaches in trials compared with clinical practice.

Developing consensus on core outcome domains for assessing effectiveness in perioperative pain management: results of the PROMPT/IMI-PainCare Delphi Meeting.

Postoperative pain management is still insufficient, leading to major deficits, including patient suffering, impaired surgical recovery, long-term opioid intake, and postsurgical chronic pain. Yet, identifying the best treatment options refers to a heterogeneous outcome assessment in clinical trials, not always reflecting relevant pain-related aspects after surgery and therefore hamper evidence synthesis. Establishing a core outcome set for perioperative pain management of acute pain after surgery may overcome such limitations. An international, stepwise consensus process on outcome domains ("what to measure") for pain management after surgery, eg, after total knee arthroplasty, sternotomy, breast surgery, and surgery related to endometriosis, was performed. The process, guided by a steering committee, involved 9 international stakeholder groups and patient representatives. The face-to-face meeting was prepared by systematic literature searches identifying common outcome domains for each of the 4 surgical procedures and included breakout group sessions, world-café formats, plenary panel discussions, and final voting. The panel finally suggested an overall core outcome set for perioperative pain management with 5 core outcome domains: physical function (for a condition-specific measurement), pain intensity at rest, pain intensity during activity, adverse events, and self-efficacy. Innovative aspects of this work were inclusion of the psychological domain self-efficacy, as well as the specific assessment of pain intensity during activity and physical function recommended to be assessed in a condition-specific manner. The IMI-PROMPT core outcome set seeks to improve assessing efficacy and effectiveness of perioperative pain management in any clinical and observational studies as well as in clinical practice.

NCOG-16. THE IMPACT OF THE TIMING OF HEALTH-RELATED QUALITY OF LIFE ASSESSMENTS ON THE ACTUAL RESULTS IN GLIOMA PATIENTS: A RANDOMIZED PROSPECTIVE STUDY

Abstract BACKGROUND The aim of this study was to explore the impact of the timing of health-related quality of life (HRQoL) measurements in clinical care on obtained HRQoL scores in glioma patients, and the association with feelings of anxiety or depression. METHODS Patients completed the EORTC Quality of Life Questionnaires (QLQ-C30 and QLQ-BN20), and the Hospital Anxiety and Depression Scale (HADS) at two time points. All patients completed the first measurement on the day of the MRI-scan (t=0), but the second measurement (t= 1) depended on randomization; group 1 (n= 49) completed the questionnaires before and group 2 (n= 51) after the consultation with the physician. RESULTS Median HRQoL scale/item scores on t0/t1 and change scores were comparable between the two groups. Between 8-58% of patients changed to a clinically relevant extent (i.e. ≥ 10 points) on the evaluated HRQoL scales/items in about one week time, in both directions, with only 3% of patients remaining stable in all scales. The mean number of the 26 evaluated HRQoL scales/items that changed to a clinically relevant extent per patient was 7 (SD= 4). Patients with stable role functioning had a lower HADS anxiety change score. However, this association was no longer significant in the multivariable regression when corrected for confounding factors. The HADS depression score was not associated with a change in HRQoL. DISCUSSION Measuring HRQoL before or after the consultation did not impact HRQoL scores on group level. However, the large majority of patients reported a clinically relevant difference in at least one HRQoL scale/item between the two time points, which was in general not influenced by feelings of anxiety or depression. Nevertheless, these findings highlight the importance of a standardized timing (e.g. at the day of the scan, consultation or first day of treatment) of patient-reported outcome assessments in clinical trials.

Prodromal Markers of Upper Limb Deficits in FMR1 Premutation Carriers and Quantitative Outcome Measures for Future Clinical Trials in Fragile X-associated Tremor/Ataxia Syndrome.

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a rare, late-onset neurodegenerative disorder characterized by tremor and cerebellar gait ataxia, affecting premutation carriers (PMC) of CGG expansions (range, 55-200) in the fragile X mental retardation 1 (FMR1) gene. Discovery of early predictors for FXTAS and quantitative characterization of motor deficits are critical for identifying disease onset, monitoring disease progression, and determining efficacy of interventions. A total of 39 PMC with FXTAS, 20 PMC without FXTAS, and 27 healthy controls performed a series of upper extremity (UE) motor tasks assessing tremor, bradykinesia, and rapid alternating movements that were quantified using an inertial-based sensor system (Kinesia One; Great Lakes NeuroTechnologies, Cleveland, OH, USA). Sub-scores from the clinician-rated FXTAS Rating Scale were correlated with the severity scores generated by the sensor system to determine its validity in FXTAS. PMC with FXTAS had significantly worse postural and kinetic tremor compared with PMC without FXTAS (P = 0.02, 0.03) and controls (P = 0.001, 0.0001), respectively, and slower finger tap (P = 0.001), hand movement (P = 0.0001), and rapid alternating movement speed (P = 0.003) and amplitude (P = 0.04) than controls. PMC without FXTAS had significantly worse right finger tap (P = 0.004), hand movement (P = 0.01), and rapid alternating movement speed (P = 0.003) and amplitude (P = 0.02) than controls. FXTAS Rating Scale subscores significantly correlated with all tremorography scores except for finger taps and left rapid alternating movement. These findings support the use of inertial sensor quantification systems as promising measures for preclinical FXTAS symptom detection in PMC, characterization of the natural history of FXTAS, assessment of medication responses, and outcome assessment in clinical trials.

Long-term and delayed functional recovery in patients with severe cerebrovascular and traumatic brain injury requiring tracheostomy.

Data on long-term functional recovery (LFR) following severe brain injury are essential for counseling of surrogates and for appropriate timing of outcome assessment in clinical trials. Delayed functional recovery (DFR) beyond 3-6 months is well documented following severe traumatic brain injury (sTBI), but there are limited data on DFR following severe cerebrovascular brain injury. The objective of this study was to assess LFR and DFR in patients with sTBI and severe stroke dependent on tracheostomy and tube feeding at the time of discharge from the intensive care unit (ICU). The authors identified patients entered into their tracheostomy database 2008-2013 with sTBI and severe stroke, encompassing SAH, intracerebral hemorrhage (ICH), and acute ischemic stroke (AIS). Eligibility criteria included disease-specific indicators of severity, Glasgow Coma Scale score < 9 at time of tracheostomy, and need for tracheostomy and tube feeding at ICU discharge. Assessment was at 1-3 months, 6-12 months, 12-24 months, and 24-36 months after initial injury for presence of tracheostomy, ability to walk, and ability to perform basic activities of daily living (B-ADLs). Long-term functional recovery (LFR) was defined as recovery of the ability to walk or perform B-ADLs by the 24- to 36-month follow-up. Delayed functional recovery (DFR) was defined as progression in functional milestones between any 2 time points beyond the 1- to 3-month follow-up. A total of 129 patients met the eligibility criteria. Functional outcomes were available for 129 (100%), 97 (75%), 83 (64%), and 80 (62%) patients, respectively, from assessments at 1-3, 6-12, 12-24 and 24-36 months; 33 (26%) died by 24-36 months. Fifty-nine (46%) regained the ability to walk and 48 (37%) performed B-ADLs at some point during their recovery. Among survivors who had not achieved the respective milestone at 1-3 months, 29/58 (50%) were able to walk and 28/74 (38%) performed B-ADLs at 6-12 months. Among survivors who had not achieved the respective milestone at 6-12 months, 5/16 (31%) were able to walk and 13/30 (43%) performed B-ADLs at 12-24 months. There was no significant difference in rates of LFR or DFR between patients with sTBI and those with severe stroke. Among patients with severe brain injury requiring tracheostomy and tube feeding at ICU discharge, 46% regained the ability to walk and 37% performed B-ADLs 2-3 years after injury. DFR beyond 1-3 and 6-12 months was seen in over 30% of survivors, with no significant difference between sTBI and severe stroke.

Rating Scales and Performance-based Measures for Assessment of Functional Ability in Huntington's Disease: Critique and Recommendations.

Limitation of functional ability is a major feature of Huntington's disease (HD). The International Parkinson and Movement Disorder Society (MDS) commissioned the appraisal of the use and clinimetric properties of clinical measures of functional ability that have been applied in HD studies and trials to date, to make recommendations regarding their use based on standardized criteria. After a systematic literature search, we included a total of 29 clinical measures grouped into two categories: (1) performance-based measures (e.g., balance, walking, and reaching/grasping), and (2) rating scales. Three performance-based measures are rated as "recommended": the Tinetti Mobility Test for screening of fall risk and for severity assessment of mobility in patients with manifest HD (up to stage III); the Berg Balance Scale for severity of balance impairment; and the Six-Minute Walk Test for assessment of walking endurance (severity) in HD subjects with preserved ambulation. No rating scale targeting functional ability reached a "recommended" status either for screening or severity measurement. The main challenges identified in this review include applying widely accepted conceptual frameworks to the identified measures, the lack of validation of clinical measures to detect change over time, and absence of validated measures for upper limb function. Furthermore, measures of capacity or ability to perform activities of daily living had ceiling effects in people with early and pre-manifest HD. We recommend that the MDS prioritize the development of new scales that capture small, but meaningful changes in function over time for outcome assessment in clinical trials, particularly in earlier stages of HD.

Dynamics and Ultradian Structure of Human Sleep in Real Life

The temporal dynamics that characterize sleep are difficult to capture outside the sleep laboratory. Therefore, longitudinal studies and big-data approaches assessing sleep dynamics are lacking. Here, we present the first large-scale analysis of human sleep dynamics in real life by making use of longitudinal wrist movement recordings of >16,000 sleep bouts from 573 subjects. Through non-linear conversion of locomotor activity to "Locomotor Inactivity During Sleep" (LIDS), movement patterns are exposed that directly reflect ultradian sleep cycles and replicate the dynamics of laboratory sleep parameters. Our current analyses indicate no sex differences in LIDS-derived sleep dynamics, whereas especially age but also shift work have pronounced effects, specifically on decline rates and ultradian amplitude. In contrast, ultradian period and phase emerged as remarkably stable across the tested variables. Our approach and results provide the necessary quantitative sleep phenotypes for large field studies and outcome assessments in clinical trials.

P.456 - Development of novel observer-reported outcome assessments in clinical trials of patients with Duchenne muscular dystrophy

P.456 - Development of novel observer-reported outcome assessments in clinical trials of patients with Duchenne muscular dystrophy

Why Outcome Measures in Dermatology Are Becoming Patient Centric

Many “validated” treatment outcome assessments in clinical trials fail to include outcomes important to patients. This review will focus on recent efforts to revise and make patient-centric clinical trial outcomes used in psoriasis, acne vulgaris, atopic dermatitis, and hidradenitis suppurativa. Over recent years, international coalitions have been formed to revise the investigator-oriented “validated” measures (e.g., PASI, IGA) in order to incorporate outcomes important to patients These not only include quality of life (QoL) assessments but also the anatomic location, physical discomfort, and appearance. This review discusses work underway to include patients in formatting revised outcome assessments. Historically, outcome measures have been developed by clinicians and pharmaceutical companies for use in clinical trials. Nonetheless, a movement is underway supported by regulatory agencies, government officials, and patient advocacy groups to include patients in the process of redesigning clinical trial outcome measures.

Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials clinical outcome assessment endpoints workshop (October 15, 2014, Bethesda MD).

On October 15, 2014, a workshop was held on the use of clinical outcome assessments in clinical trials for high-grade glioma of the brain. This workshop was sponsored by the Jumpstarting Brain Tumor Drug Development Coalition, consisting of the National Brain Tumor Society, the Society for Neuro-Oncology, the Musella Foundation for Brain Tumor Research and Information, and Accelerate Brain Cancer Cure. It was planned and carried out with participation from the US Food and Drug Administration. The workshop also included stakeholders from all aspects of the brain tumor community, including clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and the National Cancer Institute. This report summarizes the presentations and discussions of that workshop and the proposals that emerged to move the field forward and toward greater inclusion of these endpoints in future clinical trials for high-grade gliomas.

Computer-assisted staging of chronic rhinosinusitis correlates with symptoms.

The Lund-Mackay (LM) staging system for chronic rhinosinusitis (CRS) does not correlate with clinical parameters, likely due to its coarse scale. We developed a "Modified Lund Mackay" (MLM) system, which uses a three-dimensional (3D), computerized method to quantify the volume of mucosal inflammation in the sinuses, and sought to determine whether the MLM would correlate with symptoms and disease-specific quality of life. We obtained Total Nasal Symptom Score (TNSS) and 22-item Sino-Nasal Outcome Test (SNOT-22) data from 55 adult subjects immediately prior to sinus imaging. The volume of each sinus occupied by mucosal inflammation was measured using MATLAB algorithms created using customized, image analysis software after manual outlining of each sinus. Linear regression was used to model the relationship between the MLM and the SNOT-22 and TNSS. Correlation between the LM and MLM was tested using Spearman's rank correlation coefficient. Adjusting for age, gender, and smoking, a higher symptom burden was associated with increased sinonasal inflammation as captured by the MLM (β = 0.453, p < 0.013). As expected due to the differences in scales, the LM and MLM scores were significantly different (p < 0.011). No association between MLM and SNOT-22 scores was found. The MLM is one of the first imaging-based scoring systems that correlates with sinonasal symptoms. Further development of this custom software, including full automation and validation in larger samples, may yield a biomarker with great utility for both treatment of patients and outcomes assessment in clinical trials.

S.17.04 Pragmatic outcome assessment in clinical trials with children

S.17.04 Pragmatic outcome assessment in clinical trials with children

Outcome Assessments in Clinical Trials of Cryptococcal Meningitis: Considerations on Use of Early Fungicidal Activity as a Potential Surrogate Endpoint for All-Cause Mortality.

Cryptococcal meningitis (CM) is a common disease in resource-challenged settings, with a high mortality within weeks of disease onset. Mortality remains high with current treatments, so more effective interventions are needed to decrease mortality. There has been interest in using the outcome assessment of quantification of fungus from cerebrospinal fluid as a replacement (surrogate) endpoint for all-cause mortality (ACM) as a means of decreasing sample size in randomized clinical trials in CM. To evaluate a biomarker as a potential surrogate endpoint to replace ACM requires several steps. This paper discusses the issues of determining whether the context of a disease is one where a potential surrogate endpoint is rational, the types of outcome assessments that might qualify as potential surrogates, and the process for evaluation of the evidence that a chosen biomarker is a valid replacement for ACM in the given context of use. We then apply those principles to the context of randomized clinical trials of CM.

Clinical Outcomes Assessment in Clinical Trials to Assess Treatment of Femoroacetabular Impingement: Use of Patient-reported Outcome Measures

Patient-reported outcome measures are an important component of outcomes assessment in clinical trials to assess the treatment of femoroacetabular impingement (FAI). This review of disease-specific measures and instruments used to assess the generic quality of life and physical activity levels of patients with FAI found no conclusive evidence to support a single disease-specific questionnaire. Using a systematic review of study methodology, the Copenhagen Hip and Groin Outcome Score and the 33-item International Hip Outcome Tool scored the best. Nevertheless, both of these instruments were developed recently and have not been established in the literature. Although currently used generic and activity-level measures have limitations, as well, they should be considered, depending on the specific goals of the study. Additional research is needed to assess the properties of these measures fully when used to evaluate patients with FAI.