Patient-reported Adverse Events Research Articles

Validity of Patient-Reported Outcomes Measurement Information System Physical, Mental, and Social Health Measures After Left Ventricular Assist Device Implantation and Implications for Patient Care.

A better understanding is needed of the burdens and benefits of left ventricular assist device (LVAD) implantation on patients' physical, mental, and social well-being. The purpose of this report was to evaluate the validity of Patient-Reported Outcomes Measurement Information System (PROMIS) measures for LVAD patients and to estimate clinically important score differences likely to have implications for patient treatment or care. Adults from 12 sites across all US geographic regions completed PROMIS measures ≥3 months post-LVAD implantation. Other patient-reported outcomes (eg, Kansas City Cardiomyopathy Questionnaire-12 item), clinician ratings, performance tests, and clinical adverse events were used as validity indicators. Criterion and construct validity and clinically important differences were estimated with Pearson correlations, ANOVA methods, and Cohen d effect sizes. Participants' (n=648) mean age was 58 years, and the majority were men (78%), non-Hispanic White people (68%), with dilated cardiomyopathy (55%), long-term implantation strategy (57%), and New York Heart Association classes I and II (54%). Most correlations between validity indicators and PROMIS measures were medium to large (≥0.3; p<0.01). Most validity analyses demonstrated medium-to-large effect sizes (≥0.5) and clinically important differences in mean PROMIS scores (up to 14.8 points). Ranges of minimally important differences for 4 PROMIS measures were as follows: fatigue (3-5 points), physical function (2-3), ability to participate in social roles and activities (3), and satisfaction with social roles and activities (3-5). The findings provide convincing evidence for the relevance and validity of PROMIS physical, mental, and social health measures in patients from early-to-late post-LVAD implantation. Findings may inform shared decision-making when patients consider treatment options. Patients with an LVAD, their caregivers, and their clinicians should find it useful to interpret the meaning of their PROMIS scores in relation to the general population, that is, PROMIS may help to monitor a return to normalcy in everyday life.

Remote follow-up after cataract surgery (CORE-RCT): study protocol of a randomized controlled trial

BackgroundCataract surgery has become one of the most performed surgical procedures worldwide. Postoperative management consists of routine clinical examinations to assess post-operative visual function and detect possible adverse events. Due to the low incidence of complications, the majority of clinic visits after cataract surgery are uneventful. Nonetheless, valuable time and hospital resources are consumed. We hypothesize that remote post-operative follow-up involving teleconsultations and self-assessments of visual function and health status, could be a valid alternative to face-to-face clinical examinations in selected patient groups. The practice of remote follow-up after cataract surgery has not yet been evaluated. The aim of this study is to investigate the validity, safety and cost-effectiveness of remote cataract surgery follow-up, and to report on the patients’ experiences with remotely self-assessing visual function.MethodsThis study is a multicenter, open-label, randomized controlled trial. Patients planned for cataract surgery on both eyes, without ocular comorbidities, are eligible for participation. Participants will be allocated (1:1) into one of the two study groups: ‘telemonitoring’ or ‘usual care’. Participants in the ‘telemonitoring’ group will perform in-home assessments after cataract surgery (remote web-based eye exams and digital questionnaires on their own devices). Participants in the ‘usual care’ group will have regular post-operative consultations, according to the study site’s regular practice. Outcome measures include accuracy of the web-based eye exam for assessing visual acuity and refraction, patient-reported outcome measures (visual function and quality of life), adverse events, and cost aspects.DiscussionInvestigating remote follow-up after cataract surgery fits the current trends of digitization of health care. We believe that remote self-care can be a promising avenue to comply with the increasing demands of cataract care. This randomized controlled trial provides scientific evidence on this unmet need and delivers the desired insights on (cost)effectiveness of remote follow-up after cataract surgery.Trial registrationClinicalTrials.gov: NCT04809402. Date of registration: March 22, 2021.

A toolbox of different approaches to analyze and present PRO-CTCAE data in oncology studies.

The patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is used to assess symptomatic adverse events in oncology trials. Currently, no standard for PRO-CTCAE analysis exists. Key methods of descriptive analysis and longitudinal modeling using PRO-CTCAE data from an oncology clinical trial, DRiving Excellence in Approaches to Multiple Myeloma-2 (DREAMM-2), a phase II trial of belantamab mafodotin in multiple myeloma (NCT03525678), were explored. Descriptive methods included maximum postbaseline ratings, mean change over time, ratings above a predefined cutoff, line graphs, and stacked bar charts to illustrate patient-reported adverse events at one timepoint or dynamics over time. Analysis methods involving modeling over time included toxicity over time (ToxT) (repeated measurement model, time-to-event, area under the curve analyses), generalized estimating equations (GEE), and ordinal log-linear models (OLLMs). Visualizations of PRO-CTCAE data highlighted different aspects of the data. Selection of the appropriate visualization will depend on the audience and message to be conveyed. Consistent results were obtained by all modeling approaches; no difference was found between dose groups of the DREAMM-2 study in any PRO-CTCAE item by the ToxT approach or the more sophisticated GEE and OLLM methods. Interpretation of GEE results was the most challenging. OLLM supported the interval nature of the PRO-CTCAE response scale in the DREAMM-2 study. All modeling approaches account for multiple testing (driven by the number of items). Descriptive analyses and longitudinal modeling approaches are complementary approaches to presenting PRO-CTCAE data. In modeling, the ToxT approach may be a good compromise compared with more sophisticated analyses.

Effects of COVID-19 and Influenza Vaccination on Rheumatic Diseases: Results From a Survey of Patient-Reported Outcomes After Vaccination.

This study aimed to compare the occurrence of adverse events (AEs) and disease flares after vaccination against coronavirus disease 2019 (COVID-19) and influenza in patients with autoimmune rheumatic diseases (ARDs). Between November 2021 and March 2022, a survey was conducted among patients with ARD who received COVID-19 and influenza vaccinations. The questionnaire included 11 mandatory and closed-ended questions, and the following items were collected: medical history, immunization history, type of vaccine, patient-reported AEs, flare-up of the underlying disease after vaccination, and a confirmed diagnosis of COVID-19 or influenza. We compared the occurrence of vaccine-related adverse reactions to the COVID-19 and influenza vaccines based on the survey results. Multivariate logistic regression analysis was used to identify the factors affecting AEs or disease flares and to compare the post-vaccine response to mixed and matched vaccines. We analyzed 601 adults with ARD who received the COVID-19 vaccine, with a mean age of 49.6 years (80.5% female). A total of 255 participants (42.4%) received a complete course of primary vaccination, 342 (56.9%) completed the booster dose, and 132 (38.6%) received a mixed vaccine. The frequencies of AEs (188 [52.2%] vs. 21 [5.8%]; P < 0.001) and disease flares (58 [16.2%] vs. 5 [1.4%]; P < 0.001) after COVID-19 vaccination were significantly higher than those after influenza vaccination. In the risk factor analysis, previous allergic reaction to other vaccines (odds ratio, 1.95; confidence interval, 1.07-3.70; P = 0.034) was the only factor associated with the occurrence of AEs. There was no difference in the post-vaccine responses between the mixed and matched vaccines. The results of the survey of patients with ARD revealed that patient-reported AEs and underlying disease flares after receiving the COVID-19 vaccine were significantly higher than those after the influenza vaccine.

Direct-to-Consumer Telemedicine Practices in the Health and Fertility of Men: A Systematic Review of the Literature.

Men are increasingly turning toward online direct-to-consumer (DTC) men's health platforms to fulfill their health needs. Research surrounding these platforms is lacking and the motivations and predictors underlying this online health-seeking behavior is largely unknown. This review scopes the existing literature concerning DTC men's health and identifies factors influencing engagement, as well as health outcomes of this platform. A structured search was performed following PRISMA guidelines. CINAHL via EBSCO, Embase, MEDLINE via Ovid, PsycINFO, PubMed and Web of Science were searched. Peer-reviewed quantitative and qualitative studies with a focus on demographics and characteristics of those using DTC men's health platforms, as well as studies related to patient outcomes using such platforms, were included. Ten of the 3,003 studies identified met the inclusion and exclusion criteria. Four cross-sectional descriptive studies evaluated the motivations behind men's engagement with DTC platforms. Convenience, embarrassment and health motivation were identified as predominant factors associated with DTC platform use. The review identified a lack of qualitative studies, and major limitations were noted in the quantitative studies that impacted the accuracy of findings. Six further quantitative studies explored the quality of care provided by DTC platforms. DTC platforms were found to have a varying level of adherence to established clinical guidelines, but appeared to provide satisfactory patient outcomes with low levels of patient-reported side effects and adverse events. There is a lack of research within the DTC men's health space given the infancy of the field. Important predictors and motivations underlying men's choices in accessing these platforms have been noted across several studies. However, further studies need to be conducted to investigate the psychosocial underpinnings of this behavior. Studies across a wider variety of male health conditions treated by these platforms will also help to provide insights to guide patient-centered care within the DTC landscape.

Identifying symptomatic adverse events using the patient-reported outcomes version of the common terminology criteria for adverse events in patients with non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations.

Tolerability and safety of treatments are important in oncology trials and should be informed by patient assessments. We identified the most relevant patient-reported symptomatic adverse events (AEs) to measure in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. This study selected relevant symptomatic AEs from 78 AEs available in the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Initially, symptomatic AEs were selected based on literature and product labeling reviews, and then core sets of symptomatic AEs were identified by patient and clinician interviews. Qualitative and descriptive analyses were performed using the data collected from three iterative rounds of patient interviews. During concept elicitation interviews involving 29 patients, 12 symptomatic AEs were identified and were then adapted into a 25-item PRO-CTCAE form for use in future clinical trials along with commonly used PRO measures. Cognitive interviews showed that the PRO-CTCAE items were easy to answer and appropriate for assessing the patients' experience with symptomatic AEs. This study also assessed disease symptoms, impacts, and overall patient experience. The 25-item PRO-CTCAE form captures the most relevant symptomatic AEs in this patient population, and it is available for future studies. Baseline characterization of AEs associated with this distinct patient group contributes to our broader knowledge about NSCLC and through platforms like Project Patient Voice will expand our understanding of treatment tolerability and safety for NSCLC. Ultimately, this data collection will help inform decision-making for patients, caregivers, healthcare providers, and regulators.

Clostridium difficile and other adverse events from overprescribed antibiotics for acute upper respiratory infection.

Guidelines widely recommend avoiding antibiotics for many acute upper respiratory infections (aURIs) to avert adverse events in the absence of likely benefit. However, the extent of harm from these antibiotics remains a subject of debate and could inform patient-centered decision-making. Prior estimates finding a number needed to harm (NNH) between 8 and 10 rely on patient-reported adverse events of any severity. In this analysis, we sought to estimate adverse events by only measuring comparatively severe events that require subsequent clinical evaluation. We constructed a retrospective cohort, including 51 million patient encounters. Using logistic regression models, we determined the adjusted odds ratio (aOR) of clinically detectable adverse events following antibiotic use compared with events among unexposed individuals with aURIs. Our outcomes included candidiasis, diarrhea, Clostridium difficile infection (CDI), and a composite outcome. From our analysis, 62.4% of the population received antibiotics in an aURI encounter. Observed adverse events in the antibiotic-exposed group were 54,279 and 46,936 for diarrhea and candidiasis, respectively, yielding an aOR of 1.24 and 1.61, and an NNH of 3,126 and 1,975. Observed events of CDI in the exposed group were 30,133, and aORs of isolated CDI and combined adverse events were 1.07 and 1.30, resulting in an NNH of 17,695 and 1,150, respectively. Females were more likely to be diagnosed with any adverse event. Overall antibiotics were found to result in 5.7 additional cases of CDI per 100,000 outpatient prescriptions following an upper respiratory tract infection. Despite higher NNH than previous methods of analysis, we find substantial iatrogenic harm associated with prescribing antibiotics in aURIs.

Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA).

The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide. In the study reported here (Part 2), Part 1 responders received rituximab 500 or 1000 mg at W24/26 plus ongoing leflunomide. Patients were randomized at baseline to their eventual W24 treatment group. The Part 2 primary outcome was the mean Disease Activity Score-28 joints (DAS28) at W52, based on the last observation carried forward (LOCF) analyses and a two-sided analysis of variance. Patient-reported outcomes (PROs) and adverse events were evaluated. Eighty-three patients received rituximab at W24/26 (31 rituximab→rituximab 1000 mg; 29 rituximab→rituximab 500 mg; 10 placebo→rituximab 1000 mg; 13 placebo→rituximab 500 mg). At W52, there were no significant differences in DAS28 between rituximab doses in patients originally treated with rituximab or those originally treated with placebo. In the Part 1 placebo group, the higher rituximab dose was associated with greater improvements in ACR response rates and some PROs. Adverse events were similar regardless of rituximab dose. Retreatment with rituximab 500 mg and 1000 mg showed comparable efficacy, whereas an initial dose of rituximab 500 mg was associated with lower response rates versus 1000 mg. Reduced treatment response with the lower dose in patients initially treated with placebo may have been influenced by small numbers and baseline disease activity.

Ferric Carboxymaltose in the Management of Iron Deficiency Anemia in Pregnancy: A Subgroup Analysis of a Multicenter Real-World Study Involving 1191 Pregnant Women.

Real-world evidence of the efficacy and safety of ferric carboxymaltose (FCM) infusion in Indian pregnant women with iron deficiency anemia (IDA) is lacking. To assess the efficacy and safety of intravenous (IV) FCM in Indian pregnant women with IDA in 4 weeks in a real-life scenario. This is a subgroup analysis of our previously conducted retrospective, multicenter, observational, real-world PROMISE study. Data on demographic and hematological parameters, patient-reported adverse events, and physicians' clinical impressions of efficacy and safety were analysed at 4 ± 1 week. This subgroup analysis included 1191 pregnant women in whom IV FCM resulted in a significant increase in hemoglobin (Hb) by 2.8 g/dL and serum ferritin by 30.03 μg/L at 4 weeks (P < 0.001 for both). In 103 pregnant women with severe IDA, there was a significant increase in Hb by 3.6 g/dL (P < 0.001), and serum ferritin by 16.96 μg/L (P=0.12). In 978 pregnant women with moderate IDA, significant improvement in Hb by 2.74 g/dL and serum ferritin by 33 μg/L (P < 0.001 for both) was noted. Similarly, there was a significant increase in red blood cell count, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin (P < 0.001 for all). In pregnant women with mild IDA (n = 26), Hb increased significantly by 1.99 g/dL (P < 0.001). Adverse effects were reported in 8.6% of pregnant women. No new safety signals or serious adverse effects were observed. Based on physicians' global assessment, good to very good efficacy and safety of IV FCM was noted in 99.2% and 98.6% of pregnant women, respectively. IV FCM rapidly corrected anemia in a short period of 4 weeks with favorable safety in the second and third trimester of pregnancy with all severities of IDA (severe, moderate, and mild). The physicians' favorable global assessment of FCM's efficacy and safety in pregnant women with IDA supports its use in daily clinical practice. This trial is registered with CTRI/2021/12/039065.

Shielding the Vulnerable: A Multicentre Australian Rollout of Evusheld to Patients with Chronic Lymphocytic Leukaemia (CLL-SHIELD)

Background Patients with CLL are vulnerable to COVID-19 infection and complications due to underlying immunosuppression and B-cell depleting/targeted therapy (Chatzikonstantinou, Leukemia 2021). Furthermore, CLL patients have reduced seroconversion to all available COVID-19 vaccines, despite multiple dosing (Langerbeins, Blood 2022). Tixagevimab and Cilgavimab (Evusheld) was approved for pre-exposure COVID-19 prophylaxis based on the global PROVENT study in patients at risk of inadequate vaccine response, including 383 (7.4%) with cancer, but with no specific CLL data reported (Levin NEJM 2022). Patients with CLL may derive particular benefit from passive immunization, but also may be uniquely exposed to side-effects including compound cardiac signals for both Evusheld and BTKi, and injection site bleeding from BTKi anti-platelet effects. On 17 June 2022, Evusheld became publicly available to all CLL patients in Victoria, regardless of treatment status. Herein we describe the rapid rollout of Evusheld at 2 major Melbourne centers, including the establishment of a CLL cohort (CLL-SHIELD) for prospective follow-up of toxicity and efficacy. Methods: Evusheld was offered to all patients with CLL at the Peter MacCallum Cancer Center (PMCC) and Alfred Health (AH) from 20 June 2022. The rollout occurred via email or direct clinician contact (phone or in-person) at PMCC, and via hard copy mail, e-mail or direct contact at AH. Patients consenting to Evusheld were offered enrollment onto CLL-SHIELD, with planned review of patient-reported adverse events and incidence of interim COVID-19 infections via a standard questionnaire at 3, 6, and 12 months post administration. Data are de-identified at site and aggregated for analysis, with planned sensitivity analyses for treatment-center effect. Both centers have adapted a general policy of withholding any BTKi therapy for 5 days prior to and 2 days post administration to mitigate potential injection-site bleeding risk. Results: A total of 475 patients with CLL were contacted from PMCC (n=367) and AH (n=108) in the first 5 weeks of rollout. Patient-clinician discussion took place directly in person or by phone for 251 (53%) of patients, whereas 183 were contacted only by e-mail, and 41 by hard copy mail. The proportions of patients consenting to Evusheld by initial contact methods were 77.6% (n=195) for direct contact, 29.5% (n=54) for e-mail, and 12.2% (n=5) for hard copy mail (p<0.00001). Twenty-six patients who did not respond to e-mail/mail were contacted directly by their clinicians for in-person discussions; all 26 subsequently consented to Evusheld. In total, the proportion of patients who declined Evusheld following in-person consultation was 8.3% (n=23), with a further 9.7% (n=27) currently remaining undecided. The rate of Evusheld decline for patients contacted by e-mail or mail cannot be determined as only one patient replied with a clear negative response. At data cut-off, 182 of 280 (65%) consenting patients have received or have a booking to receive Evusheld. Rollout of Evusheld is ongoing at both centers and all consenting patients will be offered enrolment onto CLL-SHIELD for prospective monitoring of efficacy and toxicity. Clinical results from the 3-month post Evusheld data-cut, including rates of adverse events and COVID-19 infection, will be presented at the meeting. Conclusion: Rapid implementation of an Evusheld program is feasible in a large CLL population. Patient uptake of Evusheld was significantly higher following direct patient-clinician contact, likely due to improved opportunities for informed discussions, although this approach places short-term strain on healthcare resources. Evusheld has high acceptance rate among CLL patients, with <10% declining pre-exposure prophylaxis following in-person consultation.

The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial (SPRINT)

<h3>Purpose/Objective(s)</h3> Standard therapy for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy (chemoRT), which is usually followed by adjuvant durvalumab. We performed a prospective trial testing sequential pembrolizumab and risk-adapted radiotherapy without chemotherapy for biomarker-selected LA-NSCLC patients. <h3>Materials/Methods</h3> Patients with AJCC version 8 stage III NSCLC or unresectable stage II NSCLC and ECOG performance status 0-1 were eligible for this trial. Subjects with PD-L1 tumor proportion score (TPS) ≥ 50% received three cycles of induction pembrolizumab (200 mg, every 21 days), underwent restaging FDG-PET/CT, received risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic tumor volume exceeding 20 cc and 48 Gy delivered to smaller lesions, all in 20 daily fractions), and then received up to 13 cycles of additional pembrolizumab. Subjects with PD-L1 TPS < 50% received concurrent chemoRT, and adjuvant durvalumab was recommended for patients without disease progression. The primary study endpoint was one-year progression-free survival (PFS) for subjects treated with pembrolizumab and radiotherapy (pembroRT), which we hypothesized would exceed 65%. Other study endpoints included 1-year overall survival (OS) and rates of clinician-scored (CTCAE v. 4.03) and patient-reported (PRO-CTCAE) adverse events observed over one year. <h3>Results</h3> Twenty-five subjects with PD-L1 TPS ≥ 50% and 12 subjects with PD-L1 TPS < 50% from three institutions were enrolled between August 2018 and November 2021. Median age was 70. Twenty-four subjects had stage II-IIIA disease, and 13 had stage IIIB-IIIC disease. Except for PD-L1 TPS, subject characteristics did not differ significantly across treatment groups. Ten out of the 12 subjects with ChemoRT received adjuvant durvalumab, and one received adjuvant osimertinib for EGFR mutation. The median follow-up duration is 15 months. Compared to patients treated with chemoRT, treatment with pembroRT has yielded numerically higher 1-year PFS (72% v. 46%, log rank p=0.232) and OS (91% v. 73%, log rank p=0.213) rates. Similar rates of grade 3 physician-scored adverse events have been observed with pembroRT (24%) and chemoRT (25%). Less severe patient-reported adverse events occurred with pembroRT compared to chemoRT (See Table). <h3>Conclusion</h3> Treatment with pembrolizumab and risk-adapted radiotherapy without chemotherapy is a promising approach for LA-NSCLC patients with PD-L1 TPS ≥ 50%. In addition to yielding high disease control rates, this strategy appears to reduce patient-reported adverse events compared to standard chemoRT and adjuvant therapy.

Evaluation of Early Cosmetic Outcome and Toxicity after 5-Fraction Stereotactic Partial Breast Irradiation in Early-Stage Breast Cancer: A Prospective Cohort Study

<h3>Purpose/Objective(s)</h3> Partial breast irradiation (PBI) is a promising approach to minimize the patient burden by reducing irradiated volumes with accelerated schedules. Stereotactic-PBI (S-PBI) using a robotic stereotactic radiation system is a less invasive modality. However, prospective data are limited regarding the course of breast fibrosis and cosmesis as objective measures. We prospectively evaluated early toxicity and cosmetic outcome in women undergoing 5-fraction S-PBI. <h3>Materials/Methods</h3> Women undergoing S-PBI for invasive carcinoma and/or carcinoma in situ were prospectively enrolled. S-PBI was delivered with a robotic radiosurgery system with a dose of 30 Gy in 5 fractions. Simultaneously, women who were not a candidate for PBI, but were undergoing whole breast irradiation (WBI) were also enrolled for comparison. Patient-reported and physician-assessed adverse events were noted. Breast fibrosis was measured with a tissue compliance meter. Cosmesis was assessed with automatic computer-based software, BCCT.core. <h3>Results</h3> In total, 204 patients (n = 103, S-PBI; n = 101, WBI) were included, of whom 197 (97%) and 133 (65%) completed a 12-month and 24-month evaluation, respectively. The amount of fibrosis in uninvolved quadrants decreased over time following S-PBI for 12 months. In contrast, this finding peaked at 6 months and further decreased at 12 months in the WBI group. The amount of fibrosis of uninvolved quadrants at 6 months was significantly lower in the S-PBI group than in the WBI group (<i>P = 0.002</i>), while that of involved quadrants or scar sites was not significantly different between groups. In the S-PBI group, patient-reported grade 3–4 events were 3% at 6 months and 0% at 12 months. Physician-assessed grade 3–4 events were 2% at 6 months and 0% at 12 months. Moreover, in the S-PBI group, most cosmetic outcomes were excellent or good (82%) at 24 months, and there was no significant cosmetic detriment from baseline (<i>P = 0.353</i>). <h3>Conclusion</h3> Patients who underwent S-PBI presented with less fibrosis affecting their uninvolved breast quadrants than those who underwent WBI. Patients showed minimal toxicity with no detrimental effect on cosmesis after S-PBI. Longer-term follow-up is ongoing and necessary.

Switching from Adalimumab Originator to Biosimilar in Patients with Hidradenitis Suppurativa Results in Losses of Response-Data from the German HS Registry HSBest.

Since 2021, adalimumab biosimilar ABP 501 can be used alternatively to adalimumab originator (ADAO) in the treatment of hidradenitis suppurativa (HS). Effectiveness and safety data remain scarce. We investigated the impact of switching from ADAO to ABP 501 on disease severity and the occurrence of adverse events (AEs) in patients with HS. We analyzed clinical data on patients enrolled in the German HSBest registry. Evaluation outcomes were assessed at three time points (baseline of originator (t0), prior to switching to biosimilar (t1) and 12 to 14 weeks after switching (t2)) and included patient-reported AEs and disease severity using the International Hidradenitis Suppurativa Severity Score System (IHS4) score. In total, 94 patients were switched from ADAO to ABP 501. Overall, 33.3% (n = 31/94) of the patients developed AEs and/or loss of response (LoR) within 12 to 14 weeks after switching. Of these, 61.3% (n = 19/31) experienced LoR but no AEs, 22.6% (n = 7/31) LoR combined with AEs and 16.1% (n = 5/31) AEs only. Our study showed that switching HS patients from ADAO to ABP 501 does significantly affect treatment effectiveness. Switching patients who are on remission maintenance therapy should be viewed critically.

How to track and register adverse events and incidents related to gastrointestinal endoscopy.

Gastrointestinal endoscopic procedures have evolved significantly in the last sixty years revolutionising the approach to the diagnostic and therapeutic spheres of medicine. Despite the advantages of using natural orifices to the bowel, adverse events (AE) may occur following endoscopy. Systematic AE registration is an objective in every realm of quality medicine. Despite the obvious advantage as a quality indicator, tracking endoscopy-related AE is not evident. The current study aimed at tracking all AE of all endoscopic procedures during a 3-month period. The three methods used were voluntary reporting by the endoscopist and by the patient in parallel with retrospective data analysis of patients' electronic medical records to allow capture of all AE and comparison of the three methods. During a 3-month period endoscopists and patients were requested to report any possible AE. At the end of the period, a systematic review of all patient files was performed to track all AE related to the endoscopic procedure or the endoscopyrelated anaesthesia. In total 2668 endoscopic procedures were reviewed. The total AE rate was 1.95%. Only half (51.9%) of all AE were voluntarily reported by endoscopists, the other half were extracted from the electronic medical record. There were no patient-reported AE. Although the majority (66.7%) of unreported AE were mild, these findings illustrate that voluntary AE reporting is unreliable. However, the retrospective tracking process proved to be difficult and time-consuming. The current study highlighted that systematic registration of all endoscopy-related AE is feasible, but challenging because of multiple hurdles. More practical methods are warranted to obtain reliable and long-term data as part of endoscopy quality measures.

Impact of Vaccine Hesitancy on Onset, Severity and Type of Self-reported Adverse Events: A French Cross-Sectional Survey.

IntroductionLittle is known about the impact of mandatory vaccination on people who are reluctant to be vaccinated, despite the potential importance in terms of public health policy.ObjectiveWe aimed to explore the relationship between vaccine hesitancy and onset, severity and characteristics of self-reported adverse events.MethodsWe used a cross-sectional online survey conducted in 2021 among a representative sample of the French population aged 18 years and older (n = 1593). All reported adverse events were analyzed and categorized by trained experts in drug safety and pharmacovigilance. Multivariate binomial regressions on the onset of self-reported adverse events, vaccine hesitancy categories and predefined responders’ characteristics were performed.ResultsOverall, 590 (37.0%) participants reported at least one adverse event, with 121 (20.5%) considered it to be severe. Proportions of reported adverse events, ranging from 18% (in non-reluctant responders) to 65% (in very reluctant responders), and their severity, ranging from 5% (non-reluctant responders) to 41% (very reluctant responders), depended highly on attitudes toward vaccination. The adverse events profile remained similar between groups. In the multivariate regression model, beyond attitude toward vaccination, younger age and female gender were significantly associated with higher reporting of vaccine adverse events.ConclusionsOur results suggest that vaccine hesitancy could be a major driver of patient-reported vaccine-related adverse events and their perceived severity. In this context, vaccinators must pay special attention to reluctant patients and inform them on the possible nocebo nature of these adverse events so as to prevent them.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-022-01220-0.

Concordance between Patients and Clinicians for Reporting Symptoms Associated with Treatment for Chronic Hepatitis C during a Pragmatic Clinical Trial

Background. Despite high efficacy rates for direct acting antiviral regimens to cure hepatitis C virus infection, many patients experience treatment-related symptoms. Accurate reporting of adverse events is mandatory to determine drug safety. Previous research in other medical conditions has documented discordance between clinician-reported and patient-reported symptomatic adverse events. Aims. To explore concordance and associated factors, between clinician-recorded and patient-reported fatigue, headache, and nausea/vomiting during a clinical trial of three treatment regimens. Methods. Data were collected between treatment start and 31 days posttreatment. Patients completed Patient-Reported Outcomes Measurement Information System measures of fatigue and nausea/vomiting and the Headache Impact Test. Clinician-recorded data were abstracted from medical records. Concordance was evaluated by weighted kappa. Demographic and clinical factors associated with concordance were identified using logistic regression models. Results. Participants included 1,058 patients treated for chronic hepatitis C (average 54.9 years; 43% Black; 59% male). Weighted kappa estimates and 95% confidence intervals between patients (no/mild vs. moderate/severe symptoms) and clinicians (not present vs. present) were fatigue ( k = 0.09 , 0.02-0.16), headache ( k = 0.08 , 0.02-0.14), and nausea/vomiting ( k = 0.20 , 0.11-0.28). Older age and having private insurance (compared to Medicaid) were associated with better headache concordance. Older age, male, absence of psychiatric condition, and ≤2 comorbidities were associated with better nausea/vomiting concordance. Conclusions. Poor concordance was observed between patient-reported and clinician-recorded symptomatic adverse events. Despite study limitations, previous literature in other conditions support these findings. Integrating patient-reported data to inform adverse event reporting would improve evaluations of treatment safety (http://CT.gov/ Registration: NCT02786537).

Using Patient-Reported Outcomes in Dose-Finding Oncology Trials: Surveys of Key Stakeholders and the National Cancer Research Institute Consumer Forum.

BackgroundPatient-reported adverse events may be a useful adjunct for assessing a drug’s tolerability in dose-finding oncology trials (DFOT). We conducted surveys of international stakeholders and the National Cancer Research Institute (NCRI) Consumer Forum to understand attitudes about patient-reported outcome (PRO) use in DFOT.MethodsA 35-question survey of clinicians, trial managers, statisticians, funders, and regulators of DFOT was distributed via professional bodies examining experience using PROs, benefits/barriers, and their potential role in defining tolerable doses. An 8-question survey of the NCRI Consumer Forum explored similar themes.Results International survey: 112 responses from 15 September–30 November 2020; 103 trialists [48 clinicians (42.9%), 38 statisticians (34.0%), 17 trial managers (15.2%)], 7 regulators (6.3%), 2 funders (1.8%)]. Most trialists had no experience designing (73, 70.9%), conducting (52, 50.5%), or reporting (88, 85.4%) PROs in DFOT. Most agreed that PROs could identify new toxicities (75, 67.0%) and provide data on the frequency (86, 76.8%) and duration (81, 72.3%) of toxicities. The top 3 barriers were lack of guidance regarding PRO selection (73/103, 70.9%), missing PRO data (71/103, 68.9%), and overburdening staff (68/103, 66.0%). NCRI survey: 57 responses on 21 March 2021. A total of 28 (49.1%) were willing to spend <15 min/day completing PROs. Most (55, 96.5%) preferred to complete PROs online. 61 (54.5%) trialists and 57 (100%) consumers agreed that patient-reported adverse events should be used to inform dose-escalation decisions.ConclusionStakeholders reported minimal experience using PROs in DFOT but broadly supported their use. Guidelines are needed to standardize PRO selection, analysis, and reporting in DFOT.

P1706: CLINICAL UTILITY OF ONLINE MONITORING OF PATIENT-REPORTED SYMPTOMS IN NEWLY DIAGNOSED PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN REAL-LIFE PRACTICE

Background: Adherence to tyrosine kinase inhibitors (TKIs) is critical to maximize clinical effectiveness of drugs in patients with chronic myeloid leukemia (CML). However, adverse events (AEs) are one of the most frequent causes for non-adherence to TKI therapy. Aims: We herein report patients’ and physicians’ perception of using a newly developed online tool for patient-reported AEs monitoring in newly diagnosed CML patients in real-life practice. We also report health-related quality of life (HRQoL) and fatigue of patients up to six months. Methods: An online platform (EMPATHY) for systematic monitoring of patient-reported AEs (including a set 22 items mainly derived from the PRO-CTCAE Item Library) was developed for the purpose of this study. Newly diagnosed CML patients within 4 weeks of first line TKI therapy were eligible. At the time of a clinical visit (after having signed informed consent), and just before the consultation with the physician, patients were provided a tablet PC to self-rate (touchscreen) their symptoms. The local clinical research staff instructed patients on study procedures and on how to complete self- reported AEs via tablet. Patient-reported AEs were displayed graphically and available, in real time, to physicians’ PC during the clinical consultation. At 3- and 6-months both patients and physicians completed a Survey assessing acceptability, satisfaction and clinical utility of using this platform. At these time points, patient-reported HRQoL and fatigue were also assessed with the FACT-G and PROMIS-Fatigue questionnaires (via paper copies), respectively. Trajectories over time were estimated using a linear mixed model for repeated measures. Results: Ninety-four newly diagnosed CML patients were enrolled between July 2020 and August 2021 in 15 centers across US and Italy. There were 43% of patients treated with imatinib and 31%, 24% and 2%, treated with nilotinib, dasatinib and bosutinib, respectively. Median age of patients was 57 years (range, 19-82 years) and 55% were male. Sokal-risk was low in 42% of patients and 34% had at least one comorbidity. The majority of them (73%) used internet on a regular basis. The platform was generally well received by patients, for example, 99% (77/78) and 94% (73/78) of them agreeing or strongly agreeing (at 3 months) that it was easy to use and improved quality of communication with their physician, respectively. Of the 21 physicians (median age of 42 years) involved, nearly all (20/21; 95%) agreed that it was a valuable tool for improving accuracy of symptomatic AE of their patients. Similar high percentages were observed at 6 months. Compliance with patient-reported HRQoL and fatigue assessments was 99%, 93% and 93% at baseline, 3 and 6 months, respectively. No statistically significant differences were observed for the FACT-G and the PROMIS-Fatigue scores over time in the overall population. Summary/Conclusion: Current data suggest that the EMPATHY platform is well accepted by patients and physicians and its use may contribute to enhance physicians’ ability to better understand symptom burden of their patients.

VAERS-reported new-onset seizures following use of COVID-19 vaccinations as compared to influenza vaccinations.

The incidence of new‐onset seizures, which we defined as de novo seizures occurring within 4 weeks of receiving any of the US Food and Drug Administration‐approved COVID‐19 vaccinations as reported in patient‐reported data compiled in the US Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System Data (CDC VAERS), has not been explored. The VAERS database contains de‐identified patient‐reported adverse events following vaccination and represents post‐marketing surveillance and analysis of vaccine safety. After adjusting for time at risk, this resulted in estimated incidence rates of 3.19 seizures per 100 000 persons per year for the COVID‐19 vaccine and 0.090 seizures per 100 000 persons per year for the influenza vaccines. A data‐driven, individualized dataset that is comprehensive and coupled with a longitudinal follow‐up in larger numbers of vaccinated individuals is needed to expand on our preliminary findings of vaccine‐related seizures.

Patient-reported outcome measurement (PROM) program in patients with lymphoma receiving intravenous therapy: Preliminary results of a prospective study using PRO-CTCAE to individualize healthcate and to reduce unscheduled appointments.

e18670 Background: PROMs have been included in cancer clinical trials but it is yet to come in daily clinical practice. Their implications in healthcare management have not been well stablished yet. We hypothesize that patients subscribed to these programs may benefit from a better self-perception of health status and might require fewer hospital admissions and emergency room visits, which could allow a reduction in the costs of treatment. Methods: “E-Res Salud” is a value-based healthcare program implemented in patients with hematological malignancies in our institution. Patients (pts) with diagnosis of any type of lymphoma in the need of treatment between 1st Jan 2019 and 31st Dec 2020 were included in our research. Inclusion in PROMs program was offered to every patient starting intravenous treatment in 2020. Pts who started treatment in 2019 and those who rejected inclusion in 2020 were considered the control arm of our study. The principal endpoint was to compare physician and patient-reported adverse events through a standardized questionnaire such as PRO-CTCAE. Secondary endpoints included association between inclusion in PROMs program and reduction of hospital admissions and emergency room visits. Results: A total of 142 pts were included in our study; 76 of them (53.5%) were included in a PROMs program. There were no differences in pts characteristics with regards of age or sex. Most frequent diagnoses were diffuse large B-cell, follicular and Hodgkin lymphoma. Adverse events (AEs) most frequently reported by physicians were hematological complications (76.1%), general (73.9%), gastrointestinal symptoms (59.9%) and infections (43.7%). When patients were asked to report AEs of higher intensity, the most frequently reported were general (31.6%), genitourinary (26.3%), gastrointestinal (23.7%), neurological (15.8%) and cutaneous (13.2%) symptoms. Patients included in PROMs program experienced reported fewer general (64.5% vs. 84.8%; p &lt; 0.05) and infectious (30.3% vs. 59.1%; p &lt; 0.05) AEs than those in the control arm. Moreover, inclusion in the PROMs program was associated with fewer number of visits to Emergencies, with 34.2% of pts vs 60% of pts not enrolled in the PROM program (p = 0.003). None of the different types of AEs were associated to an increase in the number of admissions or outpatient consultations. With such a short follow-up we have not found association between any type of AE and survival. Conclusions: This program can help to increase awareness among hematologists about patients’ perception of symptoms and what really matters to them. Our study establishes the association of PROMs with health care utilization among patients with different types of lymphoma. A longer follow-up and changes in PROMs during the treatment will be further analyzed.