Patient- versus physician-reported outcomes in rheumatoid arthritis patients treated with recombinant interleukin-1 receptor antagonist (anakinra) therapy

OBJECTIVES: To determine whether patient-reported outcomes may differentiate treatment response better than physician-reported outcomes for rheumatoid arthritis (RA) patients being treated with anakinra. METHODS: A meta-analysis was conducted using data obtained from three separate randomized controlled clinical trials (RCTs) (n = 1007). Outcomes from 6-month assessments were grouped into four categories: American College of Rheumatology (ACR) response criteria, patient-reported measures (patient-reported pain, patient global assessment, and assessment of physical function using the Health Assessment Questionnaire), physician-reported measures (tender and swollen joint counts and physician global assessment), and laboratory tests (C-reactive protein and erythrocyte sedimentation rate). Effect sizes were calculated using changes from baseline and pooled standard deviations for each of these types of outcome. RESULTS: Active treatment with anakinra was superior to placebo by ACR(20) responses in all three RCTs. Effect sizes for patient-reported outcomes were greater than for physician-reported outcomes, and also greater than ACR(20) in three of five anakinra cohorts. Across the RCTs, placebo responses were greater with physician-reported than with patient-reported outcomes. In the two studies evaluating patients with longer-standing disease, differences between pooled effect sizes for patient-reported and physician-reported outcomes were even more pronounced. CONCLUSIONS: In three pivotal RCTs, active treatment with anakinra resulted in greater improvements in patient-reported than physician-reported outcomes compared with placebo. These observations confirm those previously reported from RCTs evaluating conventional DMARDs, demonstrating better discrimination of treatment effect with patient-reported outcomes.     

Time for a new era in the evaluation of targeted therapies for patients with chronic myeloid leukemia: inclusion of quality of life and other patient-reported outcomes

Health-related quality of life (HRQOL) and other patient-reported outcomes (PROs) might be crucial in comparing effectiveness of treatments as they could provide invaluable information to better inform clinical decision-making. This is particularly true in the era of targeted therapies (TT). A systematic review was undertaken on all studies with CML patients published from 1980 to 2010 and including a PRO evaluation. Out of 619 articles scrutinized, 15 met eligibility criteria and no study was published before 1995. Six dealt mainly with interferon-based therapies, 7 with bone marrow transplantation and only 2 evaluated PROs in the context of TT. No disease-specific, validated PRO instrument for these patients was found. The main evidence being that Imatinib provides clear advantage in terms of HRQOL over interferon-based treatments. There is lack of data concerning PROs in patients treated with current TT. Documenting HRQOL and side effects of CML treatments, from the patients' perspective is needed to evaluate overall treatment effectiveness and net clinical benefit of newer therapeutic strategies.     

Health‐related quality of life assessment in randomised controlled trials in multiple myeloma: a critical review of methodology and impact on treatment recommendations

Objectives: Patients with multiple myeloma (MM) often have pronounced symptoms and substantially reduced quality of life. The aims of treatment are to control disease, maximise quality of life and prolong survival. Hence, health‐related quality of life (HRQOL) should be an important end‐point in randomised controlled trials (RCTs) in addition to traditional endpoints. We wanted to evaluate whether trials reporting HRQOL outcomes have influenced clinical decision making and whether HRQOL was assessed robustly according to predefined criteria. Methods: A systematic review identified RCTs in MM with HRQOL assessment as a study end‐point. The methodological quality of these studies was assessed according to a checklist developed for evaluating HRQOL outcomes in clinical trials. The impact of the HRQOL results on clinical decision making was assessed, using published clinical guidelines as a reference. Results: Fifteen publications presenting RCTs with HRQOL as a study end‐point were identified. In 13 trials, the author stated that HRQOL results should influence clinical decision making. We found, however, that the HRQOL data only had a limited impact on published treatment guidelines for bisphosphonates, high‐dose treatment, interferon, erythropoiesis‐stimulating agents and novel agents. Conclusion: The present review indicates that the there are still few RCTs in MM including HRQOL as a study end‐point. Systematic incorporation of HRQOL measures into clinical trials allows for a comparison of treatment arms that includes the patients’ perspective. Before the full impact on clinical decisions can be realised, the quality and methodology of collecting HRQOL data must be further improved and the results rendered more comprehensible to clinicians.     

A scoping review of heart failure transitional care quality indicators and outcomes for use in clinical care and research

Aims

There are no accepted quality indicators for transitional care following hospitalization for heart failure (HF). Current quality measures focus on 30-day readmissions without accounting for competing risks such as death. In this scoping review of clinical trials, we aimed to develop a set of HF transitional care quality indicators for clinical or research applications following hospitalization for HF.

Methods and results

We performed a scoping review using MEDLINE, Embase, CINAHL, HealthSTAR, reference lists and grey literature from January 1990 to November 2022. We included randomized controlled trials (RCTs) of adults hospitalized for HF who received a healthcare service or strategy intervention that aimed to improve patient-reported or clinical outcomes. We independently extracted data and performed a qualitative synthesis of the results. We generated a list of process, structure, patient-reported, and clinical measures that could be used as quality indicators. We highlighted process indicators that were associated with improved clinical outcomes and patient-reported outcomes that had high adherence to COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and United States Food and Drug Administration standards. From 42 RCTs included in the study, we identified a set of process, structure, patient-reported, and clinical indicators that could be used as transitional care measures in clinical or research settings.

Conclusion

In this scoping review, we developed a list of quality indicators that could guide clinical efforts or serve as research endpoints in transitional care in HF. Clinicians, researchers, institutions, and policymakers can use the indicators to guide management, design research, allocate resources, and fund services that improve clinical outcomes.     

Quality of life in gastric cancer

AIM: To summarize the empirical research on assessing quality of life (QOL) in patients with gastric carcinoma. METHODS: Literature searches were conducted in MedLine from 1966 to February 2004. RESULTS: Twenty-six studies were identified. QOL was used as an outcome measure in virtually all identified studies, such as those examining the effects of gastric cancer and various medical or surgical treatments in the patients. QOL was assessed mainly with generic measures; the social dimensions of QOL were largely neglected.The lack of gastric cancer-specific QOL measures hampers QOL research up to now.The gastric cancer-specific EORTC-QLQ-STO22 and the FACT-Ga are important additions to the arsenal of disease-specific QOL measures. In most of the studies, the label QOL is used for questionnaires, which only assess symptoms or performance status, or are physician-reported rather than patient-reported outcomes. CONCLUSION: QOL in patients with gastric cancer deserves more systematic studies, especially as one of the outcome measures in randomized clinical trials. Results of studies that include QOL in patients with gastric cancer should be applied in clinical care, which aims at improving QOL of these patients.     

Identifying the clinical domains of fibromyalgia: contributions from clinician and patient Delphi exercises

OBJECTIVE: In evaluating the effectiveness of fibromyalgia (FM) therapies, it is important to assess the impact of those therapies on the full array of domains considered important by both clinicians and patients. The objective of this research was to identify and prioritize the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials, and to approach consensus among clinicians and patients on the priority of those domains to be assessed in clinical care and research. METHODS: Group consensus was achieved using the Delphi method, a structured process of consensus building via questionnaires together with systematic and controlled opinion feedback. The Delphi exercises involved 23 clinicians with expertise in FM and 100 patients with FM as defined by American College of Rheumatology criteria. RESULTS: The Delphi exercise revealed that the domains ranked most highly by patients were similar to the domain rankings by clinicians. Pain was consistently ranked highest by both panels. Fatigue, impact on sleep, health-related quality of life, comorbid depression, and cognitive difficulty were also ranked highly. Stiffness was ranked highly by patients but not clinicians. In contrast, side effects was important to clinicians but was not identified as important in the patient Delphi exercise. CONCLUSION: The clinician and patient Delphi exercises identified and ranked key domains that need to be assessed in FM research. Based on these results, a conceptual framework for measuring patient-reported outcomes is proposed.     

A systematic review of telemedicine interventions to support blood glucose self-monitoring in diabetes.

AIMS: To evaluate evidence for feasibility, acceptability and cost-effectiveness of diabetes telemedicine applications. METHODS: MEDLINE, EMBASE, PSYCHINFO, CINAHL, Cochrane, and INSPEC were searched using the terms diabetes and telemedicine for clinical studies using electronic transfer of blood glucose results in people with diabetes. The technology used, trial design and clinical outcome measures used were extracted for trials and prospective cohort studies. Randomized controlled trials with HbA(1c) as an outcome were pooled using standard meta-analytical methods. RESULTS: We identified 539 papers among which 32 papers described 10 prospective cohort studies, 12 parallel group randomized controlled trials (RCT), three crossover trials, and one non-parallel group trial. Only two studies described full details of randomization, blinding of outcomes and dropouts and withdrawals. Electronic transfer of glucose results appears feasible in a clinical setting. Only two of the RCTs included more than 100 patients, and only three extended to 1 year. Only one study was designed to show that telemedicine interventions might replace clinic interventions without deterioration in HbA(1c). Results pooled from the nine RCTs with reported data did not provide evidence that the interventions were effective in reducing HbA(1c) (-0.1%, 95% CI -0.4% to 0.04%). CONCLUSIONS: Telemedicine solutions for diabetes care are feasible and acceptable, but evidence for their effectiveness in improving HbA(1c) or reducing costs while maintaining HbA(1c) levels, or improving other aspects of diabetes management is not strong. Further research should seek to understand how telemedicine might enhance educational and self-management interventions and RCTs are required to examine cost-effectiveness.     

How could we improve the increased cardiovascular mortality in patients with overt and subclinical hyperthyroidism?

Over the past five years several meta-analyses have evaluated the cardiovascular mortality in patients with hyperthyroidism. They assessed various studies in which different inclusion criteria were used for the analysis of the cardiovascular mortality. More selective criteria have been used in recent meta-analyses. Only prospective cohort studies were included and only cohorts using second and third generation TSH assays were chosen. In addition, only the studies where the TSH evaluation was repeated during the follow-up were selected. The results of these recent meta-analyses provide evidence that overt and subclinical hyperthyroidism, particularly in patients with undetectable serum TSH, may increase the cardiovascular mortality. However, still today, the results remain inconclusive and not sufficient enough to recommend treatment for patients with low-detectable serum TSH. The high cardiovascular risk and mortality in presence of thyroid hormone excess suggest that this dysfunction is an important health problem and requires guidelines for the treatment of patients at high cardiovascular risk. Rigorous studies are necessary to evaluate the effects of the various causes of hyperthyroidism on the clinical outcomes. Randomized controlled clinical trials are needed to assess the benefits of treatment to improve the cardiovascular mortality and morbidity of mild and overt hyperthyroidism.     

The Outcomes of Percutaneous RevascularizaTIon for Management of SUrgically Ineligible Patients With Multivessel or Left Main Coronary Artery Disease (OPTIMUM) Registry: Rationale and Design

BackgroundGuidelines endorse coronary artery bypass as the preferred revascularization strategy for patients with left main and/or multivessel coronary artery disease (CAD). However, many patients are deemed excessively high risk for surgery after Heart Team evaluation. No prospective studies have examined contemporary treatment patterns, rationale for surgical decision-making, completeness of revascularization with percutaneous coronary intervention (PCI), and outcomes in this high-risk population with advanced CAD.MethodsWe designed the Outcomes of Percutaneous RevascularizaTIon for Management of SUrgically Ineligible Patients with Multivessel or Left Main Coronary Artery Disease (OPTIMUM) registry, a prospective, multicenter study of patients with “surgical anatomy” determined to be at prohibitive risk for bypass surgery. The primary outcome is comparison of observed to predicted 30-day mortality, with secondary outcomes of patient-reported health status and the association between completeness of revascularization and clinical outcomes. Patient characteristics driving surgical risk determinations will be reported, and peri-operative risk will be assessed using validated scoring methods. Angiograms will be assessed by an independent core laboratory, and clinical events will be adjudicated.ResultsClinical outcomes assessments will include 30-day and 1-year cardiovascular events, health status at 1, 6 and 12-months, and 5-year mortality.ConclusionsOPTIMUM is the first prospective, multicenter study to examine treatment strategies and outcomes among multivessel CAD patients deemed ineligible for surgical revascularization after Heart Team assessment. This registry will provide unique insights into the clinical decision-making, revascularization practices, safety, effectiveness, and health status outcomes in this high-risk population.     

Predicting and evaluating response to omalizumab in patients with severe allergic asthma

BACKGROUND: Omalizumab is a monoclonal antibody indicated for treatment of severe persistent allergic asthma inadequately controlled despite optimal controller therapy. We investigated whether patient selection could be targeted further. METHODS: Data from seven randomized controlled omalizumab trials were analyzed to investigate whether pre-treatment patient baseline clinical characteristics could be identified that were predictive of a superior response to omalizumab. We also studied whether patients who respond to omalizumab following a course of treatment could be reliably identified. Univariate/multivariate analyses of INNOVATE data were performed to identify predictive baseline measures and further investigated in efficacy analyses of pooled data from seven studies. The best method of identifying responders to omalizumab following treatment was determined by assessing the ability of various clinical response criteria to identify responders and discriminate patient exacerbation and other outcomes. RESULTS: Baseline total immunoglobulin E (IgE) was the only predictor of efficacy in INNOVATE. However, pooled analysis showed treatment benefits irrespective of IgE levels. In omalizumab-treated patients, physician's overall assessment following a course of treatment identified 61% as responders and best discriminated treatment outcomes. CONCLUSION: Baseline characteristics do not reliably predict benefit with omalizumab. Physician's overall assessment after 16 weeks of treatment is the most meaningful measure of response to therapy.     

Reporting outcomes of definitive radiation‐based treatment for esophageal cancer: a review of the literature

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials (RCTs) of radiation‐based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation‐based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient‐reported outcomes (PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation‐based treatment for esophageal cancer.     

Outcomes and Pelvic Floor Interventions: Can We Predict?

An evolving trend in reporting outcomes after pelvic floor interventions is focusing increasingly on patient-reported outcomes as assessments of pelvic floor conditions and of results after intervention. Efforts have been made to scientifically validate patient-reported outcomes instruments and to standardize their use in clinical research. Additionally, guidelines have been published recommending minimum requirements for incorporating patient-reported outcomes in peer-reviewed publications. Although an increasing number of publications are incorporating patient-reported outcomes, how these data are being used remains unclear, as many studies are not using patient-reported outcomes data as primary end points or in definitions of cure. More widespread adoption of standardized outcomes measures will better ensure more quality clinical research as well as comparability between studies.     

Taking the patient and the patient's perspective into account to improve outcomes of care of patients with musculoskeletal diseases

Patient-reported outcome measures are commonly used in the assessment of patients with musculoskeletal diseases. The present review provides an overview of historic and recent developments, including core set recommendations for assessing patient-reported outcomes in patients with fibromyalgia, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The evidence supporting commonly used patient-reported outcomes measures is reviewed. Furthermore, various methodological approaches that can be utilized to evaluate validity and measurement precision of patient reported outcomes are introduced. Commonly used methods based on the classical test theory as well as modern approaches based on item response theory will be discussed. The review finally describes the increasing use of item response theory-based approaches used in patient-reported outcomes assessment in the musculoskeletal diseases.     

Review of randomized clinical trials of drug-eluting stents for the prevention of in-stent restenosis

Drug-eluting stents (DESs) have shown significant promise at reducing rates of restenosis and subsequent revascularization compared with bare metal stents (BMSs). The purpose of this report is to provide a systematic review of the randomized clinical trials that have evaluated the efficacy and safety of DESs. A total of 28 randomized clinical trials were identified: 21 comparing a DES (sirolimus, paclitaxel, ABT-578, actinomycin, everolimus, or 7-hexanoyltaxol) with a BMS and 7 comparing a DES with another DES (sirolimus vs paclitaxel). Early sirolimus and polymeric paclitaxel studies in low-risk populations demonstrated marked reductions in restenosis according to angiographic and clinical parameters, compared with BMSs. These promising findings led to the more recent evaluations of DESs in higher risk patients in controlled and head-to-head comparisons. In these subsequent trials, sirolimus and paclitaxel DESs continued to exceed the therapeutic potential of BMSs, with a slight but consistent angiographic advantage being observed with the sirolimus DESs.     

Perioperative care of children with sickle cell disease: A systematic review and clinical recommendations

Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to conduct a systematic, PRISMA-based review of the literature, available clinical guidelines and practice recommendations. We also aimed to extract any valuable information for the “best of available-evidence”-based prevention of perioperative adverse events in children with SCD, and highlight the most urgent priorities in clinical research. As data sources, US National Library of Medicine, Medline, National Guideline Clearinghouse, International Guideline Network, TRIP databases were searched for any content until January 2019. We also included institutional, consortia and expert group guidelines. Included were reports/guidelines in English, French, German, and Italian. Excluded were reports on obstetrical and fetal management. We identified 202 reports/guidelines fulfilling the criteria outlined above. A majority focused on visceral, cardiovascular and orthopedic surgery procedures, and only five were multicenter randomized controlled trials and two prospective randomized studies. After grading of the quality of the evidence, the extracted data was summarized into clinical recommendations for daily practice. Additionally, we designed a risk-grading algorithm to identify contexts likely to be associated with adverse outcomes. In conclusion, we provide a systematic PRISMA-based review of the existing literature and ancillary practice and delineate a set of clinical recommendations and priorities for research.     

Treatment of rheumatoid arthritis patients with abatacept and methotrexate significantly improved health-related quality of life

OBJECTIVE: This study examined the effect of abatacept, a costimulation modulator, on the health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA). METHODS: Three hundred thirty-nine patients with RA on a background of methotrexate (MTX), who participated in a multicenter, double-blind, placebo-controlled trial, were randomized to abatacept 2 mg/kg, abatacept 10 mg/kg, or placebo. HRQOL was assessed at pretreatment, and at 3, 6, and 12 months posttreatment using the SF-36 Health Survey (SF-36). Changes in SF-36 scores from baseline to 12 months were compared across treatment and placebo groups to examine HRQOL benefits of abatacept. A link between American College of Rheumatology improvement and changes in SF-36 scores was established to demonstrate the association between HRQOL outcomes and clinical response. RESULTS: After 12 months of treatment, patients randomized to abatacept 10 mg/kg showed significantly better HRQOL outcomes overall versus patients randomized to placebo (MANOVA F = 4.71, p < 0.001) or to abatacept 2 mg/kg (MANOVA F = 1.97, p = 0.05). Differences in SF-36 change scores between abatacept 10 mg/kg and placebo groups reached statistical significance on all 8 domain scales, the 2 summary measures, and the SF-36 utility index (SF-6D). Differences in SF-36 change scores between abatacept 10 mg/kg and abatacept 2 mg/kg reached statistical significance on 5 of the 8 domain scales, the physical summary measure, and the SF-6D. Improvement in HRQOL was highly related to clinical response. CONCLUSION Abatacept 10 mg/kg plus MTX demonstrated a stronger HRQOL response than placebo plus MTX. The abatacept 2 mg/kg arm showed a very weak and transient response.     

Patient-reported outcomes in cystic fibrosis

Over the past 20 years, there has been tremendous progress in the area of patient-reported outcomes (PROs). A PRO instrument is defined as any measure of a patient's health status that is elicited directly from the patient and assesses how the patient "feels or functions with respect to his or her health condition." The advances seen in clinical research regarding PROs has been mirrored in research in cystic fibrosis (CF). A large number of instruments have been used for both therapeutic and nontherapeutic clinical research for many chronic conditions. This review will summarize a history of the development of PROs and how PROs are viewed by the U.S. Food and Drug Administration. We will then review the current state of the art of patient-reported outcomes in CF, specifically addressing the evaluation of different PRO instruments in terms of their reliability and validity. Finally, we will delineate further areas for development of PROs in CF. We believe that the future of CF research will incorporate a more diverse selection of PRO outcome measures; these outcome measures ultimately may be incorporated into clinical care to standardize symptom assessment and provide information regarding the need for specific clinical interventions to improve the quality of care delivered to these patients.     

Cardiac resynchronization therapy in patients with a narrow QRS

Although cardiac resynchronization therapy (CRT) is indicated in patients with moderate to severe heart failure with a wide QRS complex (> 120 ms), current guidelines exclude many heart failure patients with a narrow QRS. Detecting mechanical dyssynchrony on echocardiography has become a promising tool in selecting patients with a narrow QRS who may respond to CRT. Several small single-center studies identified patients with a narrow QRS (using echocardiography-based dyssynchrony criteria) who responded favorably to CRT; however, the results of two recent pilot studies remain elusive. The results of the RethinQ study do not provide necessary evidence for making clinical treatment decisions in this population. The lack of definitive evidence is the strongest rationale for conducting an adequately powered, long-term, end point-driven, randomized controlled trial to investigate whether CRT therapy can improve morbidity and mortality outcomes in heart failure patients with a narrow QRS. Such a trial, the EchoCRT trial, has recently been launched.