Patient-reported tolerability of adverse events in phase 1 trials.
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ABSTRACT:
SUBMITTER: Henon C
PROVIDER: S-EPMC5519806 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Background/aimsNew classes of cancer drugs bring a range of unknown and undesirable adverse events. Adverse event monitoring is essential in phase I trials to assess toxicity and safety. In phase II, the focus is also on efficacy but robust data on adverse events continue to inform the safety and the adverse event profile. Standard, clinician-led monitoring has been shown to underestimate patients' symptoms. Hence, patient-reported adverse event monitoring has been argued to complement and improve the information on adverse events in early phase clinical trials. With advances in information technology, real-time patient self-reported adverse events in trials are feasible. This study explored the experiences and procedures for reporting adverse events in early phase trials among patients, clinical staff, and trial staff, and their views on using an electronic patient-reported outcome adverse event system in this setting.MethodsQualitative interviews were conducted with patients, purposively sampled across ages, gender, and different phases of trials, and with clinical and trial-related staff involved in early phase trials (e.g. consultants, research nurses, hospital-based trial assistants/data managers, trial unit management staff). Interviews explored patient experiences and views on current adverse event reporting processes and electronic patient-reported outcome adverse event reporting. Framework analysis techniques were used to analyse the data.ResultsInterviewees were from two hospital trusts with early phase portfolios in England and a trial unit, and included sixteen patients, five consultants, four research nurses, five hospital-based trial staff, and two trial unit staff. Interviews identified three key themes (patient experiences, data flow, and views on electronic patient-reported outcome adverse event reporting). Stakeholders emphasised the intensity of trials for patients and the importance of extensive information provision within the uncertainty of early phase trial drugs. Regular face-to-face appointments for patients supplemented by telephone contact aimed to capture any adverse events. Delayed or under-reporting of mild- or low-severity symptoms was evident among patients. Hospital-based staff highlighted the challenges of current data collection including intense timescales, monitoring by trial sponsors, and high workload. Positive views on electronic patient-reported outcome adverse events highlighted that this could provide a more comprehensive and accurate view on the side effects of new drugs. Clinical staff emphasised patient safety and the need for clear responsibilities for monitoring. The need for careful decision-making about data flow and symptom attribution was highlighted; with trial unit staff emphasising the need for clinician review.ConclusionTechnology advances mean it is timely to explore the benefits and challenges of electronic patient-reported outcome adverse event reporting. This is a complex area warranting further consideration within the trial community. We have developed an online patient self-reporting tool and a small pilot with early phase trial patients is underway.
| S-EPMC8010887 | biostudies-literature
Project description:The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation (clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021).
| S-EPMC5622864 | biostudies-other
Project description:BackgroundPromoting medication adherence is a recognized challenge for prescribers. In this study, we examine whether lower medication adherence is associated with adverse safety events in individuals with decreased estimated glomerular filtration rates (eGFRs).Study designCross-sectional baseline analysis of prospective cohort.Setting & participantsBaseline analysis of the Safe Kidney Care (SKC) Cohort Study, a prospective study of individuals with eGFRs<60 mL/min/1.73 m(2) intended to assess the incidence of disease-specific safety events. Kidney transplant recipients were excluded.PredictorSelf-reported medication adherence based on responses to 3 questions ascertaining degree of medication regimen adherence.OutcomesAdverse safety events were self-reported at baseline (class I events), such as hypoglycemia or fall thought to be related to a medication, or detected incidentally during the baseline visit (class II events), for example, hypotension or hyperkalemia. Potential drug-related problems (DRPs) were determined by analyzing participants' medications with respect to dosing guidelines based on their screening eGFRs at the time of medication reporting.MeasurementsRelationship between medication adherence and disease-specific patient safety events.ResultsOf 293 SKC participants, 154 (53%) were classified as having lower medication adherence. After multivariable adjustment, lower medication adherence was significantly associated with a class I or II safety event (prevalence ratio [PR], 1.21; 95% CI, 1.04-1.41) and potential DRPs (PR, 1.29; 95% CI, 1.02-1.63). Lower medication adherence was also significantly associated with multiple (≥2) class I events (PR, 1.71; 95% CI, 1.18-2.49), multiple class I or II events (PR, 1.35; 95% CI, 1.04-1.76), and multiple potential DRPs (PR, 2.11; 95% CI, 1.08-2.69) compared with those with higher medication adherence.LimitationsUse of self-reported medication adherence rather than pharmacy records. Clinical relevance of detected safety events is unclear.ConclusionsLower medication adherence is associated with adverse safety events in individuals with eGFRs<60 mL/min/1.73 m(2).
| S-EPMC4586079 | biostudies-literature
Project description:BackgroundClinician reporting of symptomatic adverse events (AEs) in phase I trials uses the Common Terminology Criteria for Adverse Events (CTCAE). The utility of the patient-reported outcomes (PROs) version of the CTCAE (PRO-CTCAE) in this setting is unknown. This prospective, observational study compared patient- and clinician-reported symptomatic AEs in phase I patients.MethodsPhase I study-eligible patients at Princess Margaret were surveyed with the PRO-CTCAE full-item library (78 symptomatic AEs) at baseline (BL), mid-cycle 1, and mid-cycle 2 (C2). Patient and trial characteristics, best response, and survival data were collected. Presence or absence of patient- (PRO-CTCAE) or clinician-reported symptomatic AEs were compared (kappa) at defined timepoints and overall (BL+ mid-cycle 1 + C2).ResultsOf 292 patients approached from May 2017 to January 2019, a total of 265 (90.8%) were consented, with 243 (91.7%) evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in analyses. Evaluation of overall patient-reported symptomatic AEs identified 50 PRO-CTCAE and 11 CTCAE items with 10% or greater reporting frequency. Nineteen CTCAE items were reported as 1% or less despite matched PRO-CTCAE items reporting as 10% or greater. Underreported categories included sexual health, bodily emissions, and cognition. Clinician- relative to patient-reporting frequency (ratio) demonstrated 9 symptomatic AEs with a 50-fold or more lower clinician reporting rate. Overall patient-clinician agreement for individual symptomatic AEs ranged from poor (κ = 0.00-0.19) to moderate (κ = 0.40-0.59), with discordance driven by lack of clinician reporting. Dyspnea (κ = 0.54) and peripheral neuropathy (κ = 0.63) at BL and limb edema (κ = 0.55) at C2 demonstrated the highest patient-clinician agreement.ConclusionsPoor to moderate patient-clinician agreement for symptomatic AEs suggests clinician underreporting in phase I trials. Analyses of severity and interference PRO categories are ongoing.
| S-EPMC8502480 | biostudies-literature
Project description:BackgroundAdverse event (AE) reporting in early-phase clinical trials is essential in determining the tolerability of experimental anticancer therapies. The patient-reported outcome version of the CTCAE (PRO-CTCAE) evaluates AE components such as severity and interference in daily life. The aim of this study was to correlate the grade of clinician-reported AEs with patients' reported experience of these toxicities using PRO-CTCAE.MethodsPatients with advanced solid tumours enrolled on Phase I clinical trials were surveyed using the PRO-CTCAE. Symptomatic AEs were recorded by physicians using the CTCAE. A logistic regression model was used to assess associations between CTCAE grade and PRO responses.ResultsOf 219 evaluable patients, 81 experienced a high-grade (3/4) clinician-reported symptom, and of these, only 32 (40%) and 26 (32%) patients concordantly reported these as either severe or very severe, and interfering with daily life either 'quite a bit' or 'very much', respectively. Of the 137 patients who experienced a low-grade (1/2) clinician-reported AE as their worst symptom, 98 (72%) and 118 (86%) patients concordantly reported these as either mild-moderate severity and minimally interfering with daily life, respectively. There was a statistically significant association between clinician-reported AE grade and interference. Interference scores were also associated with dose reductions.ConclusionThis is the first study to explore patient-reported severity and interference from symptomatic toxicities and compare clinician grading of the same toxicities. The study provided further evidence to support the added value of the PRO-CTCAE in Phase I oncology trials, which would make AE reporting patient-centred. Further work is needed to determine how this would affect the assessment of tolerability.
| S-EPMC9596492 | biostudies-literature
Project description:IntroductionAdverse events of radiopharmaceuticals may be underreported or remain undetected. Patients can provide information about these adverse events to enable healthcare professionals to detect, understand, and manage them more efficiently.ObjectiveIn this study, we aimed to (a) determine the type, causality, and frequency of patient-reported adverse events of radiopharmaceuticals and to (b) assess the onset, outcome, and follow-up of these adverse events from the patient's perspective.MethodsWe performed a prospective cohort study of 1002 patients who underwent a nuclear medicine examination. Using a validated questionnaire, we collected patient-reported information on adverse events that occurred immediately after administration of the radiopharmaceutical as well as those that occurred later. Adverse events were analysed, coded and assessed for causality by two independent researchers.ResultsA total of 187 (18.7%) patients reported 379 adverse events. Most patient-reported adverse events of radiopharmaceuticals belonged to the 'general disorder and administration site conditions' (42.0%) and 'nervous system disorders' (16.9%) system organ classes. Of the patient-reported adverse events, 43.0% were possibly or probably causally related to radiopharmaceuticals. We found the frequency of patient-reported adverse drug reactions to diagnostic radiopharmaceuticals to be 2.8%. No important medical events were related to the administrations of diagnostic radiopharmaceuticals. Most adverse events (80.0%) occurred shortly after administration of the radiopharmaceutical and were resolved within a few hours. Some events (20.0%) emerged after patients had left the nuclear medicine department, took longer to resolve, and sometimes prompted the patient to consult a healthcare professional.ConclusionAdverse reactions to diagnostic radiopharmaceuticals can occur, and the frequency reported by patients was found to be 2.8%, which is higher than reported in the existing literature. We hope that the results of this study increase awareness of these adverse reactions among patients and healthcare professionals.
| S-EPMC7847431 | biostudies-literature
Project description:BackgroundPatients can provide valuable information missing from traditional sources of safety data, thus adding new insights about factors that lead to preventable harm. In this study, researchers determined associations between patient-reported contributory factors and patient-reported harms experienced after an adverse event (AE).MethodsA secondary analysis was conducted of a national sample of patient-reported AEs (surgical, medication, diagnostic, and hospital-acquired infection) gathered through an online questionnaire between January 2010 and February 2016. Generalized logit multivariable regression was used to assess the association between patient-reported contributory factors and patient-reported harms (grouped as nonphysical harm only, physical harm only, physical harm and emotional or financial harm, and all three harms) and adjusted for patient and AE characteristics.ResultsOne third of patients (32.6%) reported experiencing all three harms, 27.3% reported physical harms and one additional harm, 25.5% reported physical harms only, and 14.7% reported nonphysical harms only. Patients reporting all three harms were 2.5 times more likely to have filed a report with a responsible authority (95% confidence interval [CI] = 1.23-5.01) and 3.3 times more likely to have also experienced a surgical complication (95% CI = 1.42-7.51). Odds of reporting problems related to communication between clinician and patients/families or clinician-related behavioral issues was 13% higher in those experiencing all three harm types (95% CI = 1.07-1.19).ConclusionPatients' experiences are important to identify safety issues and reduce harm and should be included in patient safety measurement and improvement activities. These findings underscore the need for policy and practice changes to identify, address, and support harmed patients.
| S-EPMC7720932 | biostudies-literature
Project description:IntroductionRadiopharmaceuticals may cause adverse events. Knowledge about adverse events from a patient's perspective could help healthcare professionals to detect, understand, and manage adverse events more efficiently when using radiopharmaceuticals. Researchers need a validated questionnaire that can be used in patients to assess adverse events with radiopharmaceuticals.ObjectiveThe aim of this study was to develop, validate the content of, and perform initial testing of a questionnaire assessing patient-reported adverse events of radiopharmaceuticals.MethodsBased on existing literature, six professionals drafted and evaluated a first version of the questionnaire. Further content validation was performed using cognitive interviews with six patients undergoing a nuclear medicine examination. After adaptations, the questionnaire was developed into a web-based questionnaire. One hundred patients undergoing nuclear examination tested this version, and the results were used to assess its acceptability and evaluate reported adverse events.ResultsQuestions and answer options were revised in the initial questionnaire to improve clarity. In addition, some questions were removed. The final version consisted of 18 questions. In the test phase, the acceptability of the questionnaire was demonstrated (e.g. 79% of the patients who received the questionnaire completed it, and the median time to complete the questionnaire was 12 min for patients who reported an adverse event). Of the 100 patients (53% men, median age 64 years), 12 reported a total of 22 adverse events. One of these adverse events had a high causal association.ConclusionAfter validation and testing, the developed questionnaire to study patient-reported adverse events of radiopharmaceuticals is a suitable and valid instrument which can be used in future research.
| S-EPMC7105441 | biostudies-literature
Project description:To estimate the cost of illness (COI) of individuals with self-reported adverse drug events (ADEs) from a societal perspective and to compare these estimates with the COI for individuals without ADE. Furthermore, to estimate the direct costs resulting from two ADE categories, adverse drug reactions (ADRs) and subtherapeutic effects of medication therapy (STE).Cross-sectional study.The adult Swedish general population.The survey was distributed to a random sample of 14 000 Swedish residents aged 18 years and older, of which 7099 responded, 1377 reported at least one ADE and 943 reported an ADR or STE.Societal COI, including direct and indirect costs, for individuals with at least one self-reported ADE, and the direct costs for prescription drugs and healthcare use resulting from self-reported ADRs and STEs were estimated during 30 days using a bottom-up approach.The economic burden for individuals with ADEs were (95% CI) 442.7 to 599.8 international dollars (Int$), of which direct costs were Int$ 279.6 to 420.0 (67.1%) and indirect costs were Int$ 143.0 to 199.8 (32.9%). The average COI was higher among those reporting ADEs compared with other respondents (COI: Int$ 442.7 to 599.8 versus Int$ 185.8 to 231.2). The COI of respondents reporting at least one ADR or STE was Int$ 468.9 to 652.9. Direct costs resulting from ADRs or STEs were Int$ 15.0 to 48.4. The reported resource use occurred both in hospitals and outside in primary care.Self-reported ADRs and STEs cause resource use both in hospitals and in primary care. Moreover, ADEs seem to be associated with high overall COI from a societal perspective when comparing respondents with and without ADEs. There is a need to further examine this relationship and to study the indirect costs resulting from ADEs.
| S-EPMC3686161 | biostudies-other
Project description:BackgroundSignificant intraprocedural adverse events (AE) are reported in children who receive anesthesia for procedures outside the Operating Rooms (NORA). No study, so far, has characterized AE in children who receive anesthesia in the operating rooms (ORA) and NORA when anesthesia care is provided by the same team in a consistent manner.Objective/aimWe used the same patient-specific Quality Assurance questionnaires (QAs), to elucidate incidences of intraoperative reported AE for children receiving anesthesia in NORA and ORA locations. Through multivariate logistic regression analysis, we assessed the association between patient's AE risk and procedure's location while adjusting for American Society of Anesthesiologists (ASA) status, age, and unscheduled nature of the procedure.Methods/materialsAfter Institutional Review Board approval, we used returned QAs of patients under 21 years, who received anesthesia from our pediatric anesthesia faculty from May 1 2006 through September 30, 2007. We analyzed QA data on: service location, unscheduled/scheduled procedure, age, ASA status, presence, and type of AE. We excluded QAs with incomplete information on date, location, age, and ASA status.ResultsWe included 8707 cases, with 3.5% incidence of reported AE. We had 1898 NORA and 6808 ORA cases with AE incidence of 2.5% and 3.7%, respectively. Multivariate regression analysis revealed that patients with higher ASA status or younger age had higher incidence of reported AE, irrespective of location or unscheduled nature of the procedure. The most common AE type, for both sites, was respiratory related (1.9%).ConclusionsPediatric reported AE incidence was comparable for NORA and ORA locations. Younger age or higher ASA status are associated with increased risk of AE.
| S-EPMC2752696 | biostudies-literature