Patient-reported Outcomes In Clinical Trials Research Articles

Patient-reported outcomes in hemodialysis vascular access: A call to action.

While access-related dysfunction is a clear driver of clinical outcomes and costs, the full impact of vascular access dysfunction on patient experience and quality of life is not fully characterized in the literature. One way to more comprehensively characterize the patient experience from the patient perspective is through patient reported outcomes (PROs). However, the limited implementation of PROs in clinical trials, patient registries, quality measurement, and other research settings has significantly constrained the patient voice in evaluation of vascular access outcomes and vascular access decision-making. To address these issues, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the U.S. Food and Drug Administration, assembled an interdisciplinary workgroup to enhance uptake of access-related PROs with the aims of: (1) reviewing the domains of HRQOL that are affected by vascular access, collect information on existing instruments that measure access-specific HRQOL in hemodialysis, and identify gaps in existing measures; (2) identifying and critically assessing barriers to widespread use of access-specific PRO measures; and (3) defining initiatives to overcome barriers and make recommendations for strategies to improve the use and utility of access-specific PRO measures. A consensus group process identified potential barriers to use of PRO measures in six categories: (1) PRO misperceptions, (2) patient factors, (3) regulators and payers, (4) instrument factors, (5) study design, and (6) physicians. The workgroup provided recommendations for actions to promote the widespread utilization of vascular access-related PRO measures in five categories: (1) development of vascular access-specific PRO measures, (2) ensuring comprehensive assessment when using vascular access PRO measures, (3) ensuring accessibility and applicability of vascular access PRO measures to all end stage kidney disease populations, (4) establishing universal guidelines and accepted vascular access PRO measures, and (5) engaging stakeholders across all facets.

Patient-reported outcomes in clinical trials for multiple myeloma: Where we are.

e18615 Background: It is recommended to include patient-reported outcomes (PROs) in cancer trials to ensure clinical benefit based on patients’ perceptions. For multiple myeloma patients, PRO measurement is essential to understand the impact of treatment on their physical and psychosocial functional behaviour. However, it is unclear which PRO instruments are utilized in multiple myeloma trials, how often they are used and whether results are consistently reported. The aim of this project was to explore the use and frequency of PRO instruments in randomized controlled trials for multiple myeloma and to assess the consistency of their reporting. Methods: Within the European Hematology Association (EHA) project to develop guidelines for the use of PROs in adult patients with hematological malignancies, MEDLINE and CENTRAL were systematically searched for randomized controlled trials investigating multiple myeloma between 2015 and 2020. Study design, disease and treatment characteristics, the primary outcome and used PRO instrument(s) were extracted using a pre-defined template. To assess the consistency of PRO reporting, study registries were compared with publications, study protocol and Health Technology Assessment (HTA) reports where available. Results: Overall, 10,707 records were found. Following screening for randomized-controlled trials, 283 ongoing, completed or published studies were included for review. 118 studies planned the use of PROs. The most frequently used PRO instrument (92 studies) was the EORTC QLQ-30, an instrument that measures health-related quality-of-life (HRQoL) in cancer patients. The disease-specific questionnaire EORTC-MY20 was also frequently used (50 studies). Likewise, the HRQoL instrument EQ-5D was used in 50 studies. Overall, 38 different PRO instruments were reported. In 39 studies for which a study protocol was found, only 19 reported PRO instruments consistently with the trial registry for the study. In addition, in 30 studies, for which a publication reported PRO results (58 overall), the information on PRO instruments differed between publication and the trial registry. For example, PRO instruments mentioned in the registry were omitted in the respective publications. Additionally, information on PRO in HTA reports was available for 26 studies, of which 18 reports were consistent with the trial registries. Conclusions: The results show that measurement of PROs still remain under-utilized in multiple myeloma research. While most PRO instruments identified in this review comply with the recommendations for incorporating PROs into clinical research in adult oncology, they are often inconsistently reported. Thus, reporting standards for the use of PROs are needed to ensure consistency in the use and reporting of PROs.

The Importance of a Detailed Geriatric Functional Assessment of Older Patients with Cancer

Background: For older patients with cancer, maintaining or regaining their ability to care of themselves is of major interest. Which tools are appropriate to measure this? Different tools to assess functional status (FS) are established in geriatric and oncological care, but they have been compared poorly in the past. Patients and Methods: Within a prospective cohort trial, we included 483 patients: 198 older patients with cancer, 156 younger patients with cancer, and 129 older patients with benign disease. FS was assessed as Eastern Cooperative Oncology Group performance status (ECOG-PS), activities of daily living (ADL), and instrumental activities of daily living (IADL). Results were compared for their differences in identifying patients as functionally compromised. Summary: The relative frequency of cancer patients with limitations in ECOG-PS, ADL, and IADL, respectively, increased from 25.7, 13.5, and 17.9% in those <60 years of age to 50.0, 47.1, and 66.7% in those ≥80 years. Results in older patients with cancer were comparable to older patients with benign disease. In older patients with cancer, 20.7 and 21.6% with a good ECOG-PS had limitations in ADL and IADL, respectively; of those without limitations in ADL and IADL, 34.7 and 26.0%, respectively, had a poor ECOG-PS. Treatment approach (curative vs. palliative) was found to be significantly associated with functional limitations. Key Messages: Geriatric and oncological measure of FS report differences in functional impairment. Geriatric functional measures are more sensitive to age-related changes and should be included as patient-reported outcomes in clinical trials and care.

Comments on 'Longitudinal Analysis of Patient-Reported Outcomes in Clinical Trials: Applications of Multilevel and Multidimensional Item Response Theory'.

Comments on 'Longitudinal Analysis of Patient-Reported Outcomes in Clinical Trials: Applications of Multilevel and Multidimensional Item Response Theory'.

Patient-Reported Outcomes in Clinical Trials Leading to Cancer Immunotherapy Drug Approvals From 2011 to 2018: A Systematic Review.

Patient-reported outcomes (PROs) promote patient centeredness in clinical trials; however, in the field of rapidly emerging and clinically impressive immunotherapy, data on PROs are limited. We systematically identified all immunotherapy approvals from 2011 through 2018 and assessed the analytic tools and reporting quality of associated PRO reports. For randomized clinical trials (RCTs), we developed a novel 24-point scoring scale: the PRO Endpoints Analysis Score based on 24 criteria derived from the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. We assessed 44 trial publications supporting 42 immunotherapy approvals. PROs were published for 21 of the 44 (47.7%) trial publications. Twenty-three trials (52.3%) were RCTs and 21 (47.7%) pertained to single-arm trials. The median time between primary clinical outcomes publications and their corresponding secondary PRO publications was 19 months (interquartile range = 9-29 months). Of the 21 PRO reports, 4 (19.0%) reported a specific hypothesis, and most (85.7%) used descriptive statistics. Three (3 of 21 [14.3%]) studies performed a control for type I error. As for RCTs, 14 of 23 (60.9%) published PRO data, including 13 (56.5%) that published a secondary dedicated manuscript. One-half of these 14 trials scored less than 13 points on the 24-point PRO Endpoints Analysis Score. The mean score was 12.71 (range = 5-17, SD = 3.71), and none met all the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. Suboptimal reporting of PROs occurs regularly in cancer immunotherapy trials. Increased efforts are needed to maximize the value of these data in cancer immunotherapy development and approval.

Response to 'hepatitis C cure improved patient-reported outcomes in patients with and without liver fibrosis in a prospective study at a large urban medical center'.

Patient-reported outcomes (PROs) are important measures of quality of life. Direct-acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA-based HCV cure on PROs and liver-related outcomes in real-world patients at a large urban medical centre. The Short Form (SF)-36 and three additional validated instruments were used. F3-4 fibrosis was defined as >9.6 kPa by transient elastography (TE); S2-3 steatosis was defined as >270 dB/m by TE-controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n=16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF-36 vitality score, measured baseline to SVR12: 63 vs 82, P<.001 (n=111). Scores in 24 of 25 PRO domains improved at SVR12 (P<.05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (p<0.005), but steatosis was unchanged (p=0.58). Patients with baseline F0-2 fibrosis and those with F3-F4 fibrosis both improved in 22 domains. Patients with baseline S0-S1 steatosis improved in more domains (23) than patients with S2-S3 steatosis (19). At baseline, patients with F3-F4 fibrosis and patients with S2-3 steatosis had worse scores in certain PRO domains than patients with F0-2 fibrosis or S0-S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment.

International guidance on the selection of patient-reported outcome measures in clinical trials: a review.

Patient-reported outcomes (PROs) are increasingly used in clinical trials to provide patients' perspectives regarding symptoms, health-related quality of life, and satisfaction with treatments. A range of guidance documents exist for the selection of patient-reported outcome measures (PROMs) in clinical trials, and it is unclear to what extent these documents present consistent recommendations. We conducted a targeted review of publications and regulatory guidance documents that advise on the selection of PROMs for use in clinical trials. A total of seven guidance documents from the US Food and Drug Administration, European Medicines Agency, and scientific consortia from professional societies were included in the final review. Guidance documents were analyzed using a content analysis approach comparing them with minimum standards recommended by the International Society for Quality of Life Research. Overall there was substantial agreement between guidance regarding the appropriate considerations for PROM selection within a clinical trial. Variations among the guidance primarily related to differences in their format and differences in the perspectives and mandates of their respective organizations. Whereas scientific consortia tended to produce checklist or rating-type guidance, regulatory groups tended to use more narrative-based approaches sometimes supplemented with lists of criteria. The consistency in recommendations suggests an emerging consensus in the field and supports use of any of the major guidance documents available to guide PROM selection for clinical trials without concern of conflicting recommendations. This work represents an important first step in the international PROTEUS Consortium's ongoing efforts to optimize the use of PROs in clinical trials.

The State of the Science in Patient-Reported Outcomes for Patients with Lung Cancer.

Traditionally, clinicians have assumed the primary responsibility for evaluating disease- and treatment-related outcomes. In the past few decades, however, a series of recommendations and standards promulgated by professional societies and regulatory agencies have resulted in increased use of patient-reported outcome (PRO) measures in cancer clinical trials. PROs, such as quality of life (QOL) measures, are important in establishing overall treatment effectiveness in cancer clinical trials, and they can inform clinical decision making. This article discusses the current state of the science in PRO research for patients with lung cancer, the cancer type with the highest incidence rate and the lowest survival rate worldwide. The discussion focuses on (1) PRO and survival; (2) electronic PRO reporting and interventions; (3) PROs and immunotherapy; (4) PRO, biomarkers, and precision health; (5) key issues in applying PROs in clinical trials; and (6) future directions for research.

Ductal carcinoma in situ (DCIS): The importance of patient-reported outcomes (PRO).

Patient reported outcomes (PROs) are an optimal method for assessing quality of life (QOL), including physical and psychosocial health. This review summarizes PROs frequently assessed in the setting of a DCIS diagnosis. Health-related QOL has generally been found to be modestly affected in women with DCIS and similar to women with invasive breast cancer. Several studies reported a substantial negative impact on sexual health and body image, including some differences based on surgery type. Some patients experience pain after treatment, although many physical symptoms resolve. The prevalence of anxiety and depression varied based on assessment timing, with symptoms improving over time. Women with DCIS often overestimate the risks associated both with DCIS and invasive cancer. PROs provide critical information regarding the experiences of women following a DCIS diagnosis. Continued inclusion of PROs in clinical trials is warranted, further informing treatment decisions and adequately preparing patients for what to expect following treatment.

Impact of depressive symptoms on self-perceived severity of autonomic dysfunction in multiple system atrophy: relevance for patient-reported outcomes in clinical trials.

To assess the relationship between depressive symptoms and self-perceived severity of autonomic dysfunction in patients with multiple system atrophy (MSA). Cross-sectional evaluation of patients with MSA who underwent autonomic testing, Unified MSA Rating Scale (UMSARS)-1 and -2, rating of the presence and severity of depressive symptoms (Zung scale), quality of life (SF-36), body vigilance, anxiety (Spielberger's anxiety scale), severity of autonomic dysfunction with the Composite Autonomic Symptoms Score (COMPASS-31), and severity of orthostatic hypotension (OH) symptoms with the Orthostatic Hypotension Questionnaire (OHQ). Fifty-eight patients (32 women) with probable MSA (aged 61.8 ± 8.6years; disease duration 4.3 ± 2.1years) were studied. Forty patients (69%) had symptoms of depression in the Zung scale. Age, disease duration, and motor disability were similar in those with and without symptoms of depression. Despite a similar orthostatic blood pressure fall, the severity of orthostatic symptoms was higher in patients with symptoms of depression (p = 0.004). Depression scores were associated with higher burden of autonomic symptoms (R = 0.401, p = 0.02), specifically with the COMPASS-31 items related to orthostatic intolerance (R = 0.337, p = 0.045), and with the OHQ (R = 0.529; p < 0.001). A multivariable regression model including age, sex, UMSARS, and drop in systolic blood pressure upon head-up tilt as covariates showed that the burden of depressive symptoms was independently associated with the OHQ score: for every 1-unit increase in the Zung depression score, there was a 1.181-point increase in the total OHQ score. In patients with MSA, depressive symptoms worsen the perceived severity of autonomic symptoms in general and orthostatic hypotension in particular. Our findings have implications for clinical trial design.

Hepatitis C cure improved patient-reported outcomes in patients with and without liver fibrosis in a prospective study at a large urban medical center.

Patient-reported outcomes (PROs) are important measures of quality of life. Direct-acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA-based HCV cure on PROs and liver-related outcomes in real-world patients at a large urban medical center. The short form (SF)-36 and three additional validated instruments were used. F3-4 fibrosis was defined as>9.6kPa by transient elastography (TE); S2-3 steatosis was defined as>270dB/m by TE-controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n=16) who did not achieve a sustained virologic response at 12weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF-36 vitality score, measured baseline to SVR12: 63 versus 82, P<.001 (n=111). Scores in 24 of 25 PRO domains improved at SVR12 (P<.05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P<.005), but steatosis was unchanged (P=.58). Patients with baseline F0-2 fibrosis and those with F3-F4 fibrosis both improved in 22 domains. Patients with baseline S0-S1 steatosis improved in more domains (23) than patients with S2-S3 steatosis (19). At baseline, patients with F3-F4 fibrosis and patients with S2-3 steatosis had worse scores in certain PRO domains than patients with F0-2 fibrosis or S0-S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment.

Under Reporting of Patient Reported Outcomes (PROs) in Myeloproliferative Neoplasm (MPN) Clinical Trials

Introduction Improvements in overall survival (OS) and quality of life (QoL) are clinically relevant outcomes that should guide clinical decision-making. Patients with MPNs can live with their disease for a long period of time, which increases the importance of understanding the impact of treatment in regards to a patients' Health-Related QoL. Therefore, including PROs in clinical trials has become paramount in facilitating informed treatment decisions made by health care providers and patients. Furthermore, the FDA encourages the implementation of patient-centric measures in clinical trials. Objective We aimed to evaluate the frequency at which PRO measures are utilized as study endpoints and are made publicly available when trial results are published. Methods A review was conducted to characterize studies that have evaluated PRO in patients undergoing treatment for myeloproliferative neoplasms. We searched Citeline® Trialtrove database, a registry of clinical trials, for randomized clinical trials including patients with all myeloproliferative neoplasms, initiated between the years 2006-2016, utilizing at least 1 PRO. We excluded trials that evaluated supportive care and studies with no publications. For included trials, we recorded the following data: indication, treatment and comparator, clinical development phase, endpoints, trial sponsorship, and type of scale or questionnaire used for PRO endpoint. We then identified all available publications associated with the trial, and recorded type of publication (abstract or full text), year, number of randomized patients, and reported outcomes. Results Thirty-five MPN trials were obtained through our search. Trials included patients with chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis, and mastocytosis. Of these 35 trials, 16 were excluded; two studies were classified as supportive care, three studies did not have a publication or were terminated without results, and 11 studies did not have at least one PRO. 19 trials (19/30; 63%) included at least one PRO assessment as an endpoint and were included in the analysis. Among these 19 trials, the commonly used PRO assessments were EQ-5D, EORTC-QLQ C30, Total Symptom Score (TSS), FACT-Leu, FACT-G, MPN-SAF, and Patient Global Impression of Change (PGIC). Three of the 19 trials (15.8%) utilized at least one PRO as a primary endpoint. Among the 19 trials, thirteen (68.4%) were sponsored by industry, three (15.8%) were sponsored by industry-academic collaborations, and three (15.8%) were sponsored solely by academic institutions. 12 studies (63.2%) reported PRO results within their publications. Six studies (31.6%) reported PRO data within their initial publication. Nine of the19 trials (47.4%) included a comprehensive report of PRO data within their publications, while three (15.8%) only partially reported PRO data. Of the 12 trials with published PRO data, four of 12 (33.3%) reported the PRO more than six months after the initial full publication. Most of the included trials focused on disease control outcome and overall survival benefit was not shown. Conclusions: Despite a growing emphasis on QoL and the inclusion of PROs in oncology clinical trials, a significant number of the observed MPN randomized trials did not include a PRO measure. Of those trials that included a PRO measurement, many lacked the comprehensive reporting needed to inform the assessment of clinical benefit and respective decisions. Early and timely reporting of PRO data should be valued, especially in this indication; however, the publication of PRO data along with other critical trial endpoints was not seen in many of the initial trial reports. The collection of PRO data should result in routine, timely, and appropriate reporting as part of the trial outcome publication, to allow for a thorough assessment of investigational clinically relevant treatment effects. If the primary trial publication does not include the PRO results, there should be a reference or acknowledgment to the impending PRO publication. Future research in this field may evaluate the reasons why PROs are not implemented more often in clinical trials and what causal factors have influenced the under-reporting of PRO data in trial publications. Table Disclosures No relevant conflicts of interest to declare.

Responder rates to fampridine differ between clinical subgroups of MS patients and patient reported outcome influences treatment decision making

BackgroundFampridine is an effective treatment to improve ambulation for some multiple sclerosis (MS) patients. Remarkable discrepancies exist between responder rates in clinical trials and the proportion of patients continuing treatment in clinical practice. This may be related to clinical phenotypes of MS patients, and the influence of patient reported outcome (PRO) on treatment decision making. ObjectiveTo analyse responder rates to fampridine on ambulation and upper extremity function (UEF) and the influence on treatment decision making in different clinical subgroups in a real-world setting. MethodsMS patients with ambulatory impairment treated with fampridine were included. Patients were subdivided based on disease duration, clinical phenotype, Expanded Disability Status Scale (EDSS), baseline walking speed, and presence of UEF impairment. Ambulatory response was assessed with the Timed 25-Foot Walk (T25FW, responder defined as ≥20% improvement) and with the MS Walking Scale (MSWS, responder defined as ≥8 points improvement) as a PRO. For patients also reporting impaired UEF, the Arm Function in MS Questionnaire (AMSQ, responder defined as ≥15 improvement) was the PRO of choice. Decision on treatment continuation was based on improvement of T25FW, MSWS and the clinicians’ overall impression for improvement. ResultsIn total 344 patients were included of which 75.3% continued treatment. More patients with a relapsing clinical phenotype continued treatment vs patients with a progressive phenotype (83.6 vs 68.6%, p < 0.01).A positive linear trend was found between severity of walking disability, as determined by baseline walking speed, and T25FW response (p < 0.01), while there was an inverse linear association between walking disability and MSWS response (p = 0.03). However, the proportion of patients continuing treatment was similar between subgroups of baseline walking speed. Impaired UEF was reported by 183 (66.5%) patients, of which 64 (39.3%) were AMSQ responders. Patients responding on AMSQ compared to non-responders, were also more frequently MSWS responders (82.8 vs 65.3%, p = 0.02), while response on T25FW was similar, and continued treatment more often (85.9 vs 70.7%, p = 0.04). This suggests an influence of PRO on treatment decision making. ConclusionResponder rates and treatment continuation of fampridine differed between clinical subgroups of MS. PROs influenced treatment decision making of fampridine in clinical practice, particularly in patients with mild ambulatory impairment or those reporting UEF impairment. To some extent, these findings explain discrepancies found between clinical trials and clinical practice, and support the importance of subgroup analyses and incorporation of PROs in clinical trials. For clinical practice, using PROs to assess patients experience in conjunction with performance measures helps in treatment decision making.

Patient Reported Outcomes in Metastatic Breast Cancer Studies: Evaluating the Impact of the FDA Guidance for Industry

Introduction: Over the last two decades, a number of new therapies have demonstrated improved overall survival in metastatic breast cancer (MBC) [10]. Despite these advances, MBC remains incurable with a median survival of less than three years [7, 10, 11, 15]. Prolonging survival and maintaining quality of life (QoL) continue to be the central goals of therapy. Unlike the early stages of breast cancer, the management of MBC is less clearly defined, with no specific treatment recognized as the standard of care [15]. Several studies have sought to determine an optimal regimen for the management of MBC with aims to prolong survival, however relatively few adequately powered studies have directly addressed QoL [8]. Patient reported outcomes (PROs) are instruments used to elicit the patient experience thereby gaining insight into a particular health state and aiding in the assessment of QoL [5]. As the prevalence of PROs grew, the FDA released in December 2009 an industry guidance on the implementation of PROs in clinical trials for the development of medical products and to support labeling claims [1]. This study was undertaken with aims to evaluate the impact of the FDA guidance on the use of PROs as standard endpoints in randomized phase two or three clinical trials assessing therapeutic options in MBC. Methods: Clinicaltrials.gov’s advanced search tool was used to capture registered interventional phase two or three clinical trials in adult patients with MBC conducted in the United States that began recruitment between January 1, 2002 and December 31, 2017. Trials with QoL or PROs listed as primary or secondary endpoints on Clinicaltrials.gov were subsequently identified. Segmented regression analysis of the interrupted time series data [18] was used to estimate dynamic changes pre and post adoption of the FDA guidance. Results: A total of 677 studies were identified, 72 of which used PROs. Prior to adoption of the FDA guidance, there is a nonsignificant trend towards increasing PRO use at a rate of 0.4% per year (p > 0.05). At the time of adoption, there is a one-time nonsignificant increase of 0.6% in PRO use (p > 0.05). After adoption, there is a nonsignificant trend towards decreasing PRO use at a rate of 0.3% per year (p > 0.05). Discussion: Our study results demonstrated that despite the FDA guidance, there has been little change in the use of PROs as endpoints in MBC studies. This missed opportunity to elicit the patient experience inherently limits evidence often used to counsel patients and support their decision-making framework as they focus on their priorities in selecting treatment options.

Graft Versus Host Disease Clinical Trials: Is it Time for Patients Centered Outcomes to Be the Primary Objective?

Graft versus host disease (GVHD) is a common complication following hematopoietic cell transplant and is associated with a high symptom burden, reduced functional status, and impaired quality of life (QOL). QOL is best assessed by patient-reported outcomes (PRO). Numerous clinical trials for the prevention and treatment of GVHD are available. This review aims to understand the landscape of PRO inclusion in clinical trials for GVHD over the last decade. Consensus bodies, including experts in GVHD, PRO, and clinical trials have made recommendations for a standardized approach for the inclusion of PRO in clinical trials including as primary outcomes, however, these have yet to be implemented in a consistent manner in practice. Consistently applying consensus recommendation in chronic GVHD will ensure that PROs are appropriately included in clinical trials. Development of validated measures in acute GVHD and composite outcomes for all GVHD trials are required.

The importance of patient-reported outcomes in clinical trials and strategies for future optimization.

Patient-reported outcomes (PROs) can be included in clinical trials as primary or secondary endpoints and are increasingly recognized by regulators, clinicians, and patients as valuable tools to collect patient-centered data. PROs provide unique information on the impact of a medical condition and its treatment from the patient’s perspective; therefore, PROs can be included in clinical trials to ensure the impact of a trial intervention is comprehensively assessed. This review first discusses examples of how PRO endpoints have added value to clinical trial interpretation. Second, it describes the problems with current practices in designing, implementing, and reporting PRO studies, and how these problems may be addressed by complying with guidance for protocol development, selecting appropriate PRO measures to match clinically motivated PRO hypotheses, minimizing the rates of avoidable missing PRO data, analyzing and interpreting PRO data, and transparently reporting PRO findings.

The Evolution of Patient-Reported Outcomes in Clinical Trials and Management of Patients With Coronary Artery Disease

The Evolution of Patient-Reported Outcomes in Clinical Trials and Management of Patients With Coronary Artery Disease

PCP11 - Patient Reported Outcomes (PRO) In Oncology, What Beyond Randomized Controlled Trials?

The use of PRO in oncology trials is increasing and the use of PRO in clinical trials translates into the use of PRO in FDA labels. We sought to review to what extent PRO data is used by doctors and patients in real-life settings. Literature review. Many cancer-specific PRO instruments exist that have been developed to measure HRQL or symptoms relevant in a given cancer. Improvements in HRQL have been shown in treatment with certain biological therapies for cancers and PROs have been shown to correlate with survival in patients receiving cancer therapy. PROs are often better predictors of survival than performance status, but studies are needed to determine whether interventions that improve PROs also increase survival and to identify explanatory mechanisms through which PROs relate to survival. However, PROs are rarely used in non-trial settings. This means that oncologists cannot track patients progress or satisfaction with treatment in the clinic where PRO tools are not available. Also, clinicians may not understand the trade-offs the patients are willing to make between improvements in objective biological outcomes such as e.g. tumour shrinkage and possible worsening in other symptoms or HRQL. Therefore, the potential of PRO use beyond clinical trials remains underutilized. There is a need to develop a guidance and clinician training programs on the use of PRO tools in the clinic in order to utilise their potential to inform clinical decisions and to enhance the dialogue between the doctors and patients.

Assessing the severity of atopic dermatitis in clinical trials and practice

There is a tremendous need for accurate and reproducible scoring systems for the grading of skin disease to further the development of research and standards of care. There are presently greater than 60 measures that have been used to assess the severity of atopic dermatitis. These assessments vary considerably with respect to content, scale, instructions, validity, and concordance. This contribution reviews the available scoring systems of atopic dermatitis signs based on their design and merit in specific settings. These scores assess lesional intensity and/or extent, symptoms, disease course, and epidermal function. Scoring atopic dermatitis, Investigator Global Assessment, and Eczema Area and Severity Index are the most commonly used assessments of atopic dermatitis signs. Eczema Area and Severity Index has emerged as the preferred outcome measure of atopic dermatitis signs for use in clinical trials. Unfortunately, Eczema Area and Severity Index can be cumbersome in clinical practice. Itch intensity (visual analog or numeric rating scales) and Patient-Oriented Eczema Measure have emerged as the preferred patient-reported outcome in clinical trials. Clinicians’ gestalt global assessment of severity, Patient-Oriented Eczema Measure, and intensity of itch may be feasible for clinical practice.

A practical guide to understanding, using and including patient reported outcomes in clinical trials in ovarian cancer.

Health related quality of life (HRQOL) is a key priority for patients with ovarian cancer as there is significant morbidity associated with the disease and the treatment. It is therefore essential to include measures of HRQOL and patient reported outcomes (PROs) in all clinical trials and ideally report them in the initial manuscript. The results of these analyses help interpret the primary trial endpoints which are typically progression free survival and overall survival from the perspective of the patients, but can also assist with regulatory approval of new drugs and inform future patients regarding the potential benefits and downsides of the treatment as well as help support clinical recommendations. Including PROs in clinical trials allows patient-defined clinical benefits to be assessed in parallel to traditional survival outcomes to provide a more holistic overview and aid in the interpretation of the trial results. Given the importance of these instruments in clinical trials, greater effort is required to improve the appropriate inclusion, quality of analyses and reporting of PROs. It is also essential that all clinicians understand the intricacies of the selection, implementation and interpretation of these measures of HRQOL and PRO's and how important their contribution is to clinical trials as well as clinical practice. This review is a practical guide for clinicians to gain a better understanding of PROs and how they can be incorporated into ovarian cancer trials.