The Importance of Direct Patient Reporting of Adverse Drug Reactions in the Safety Monitoring Process

All medicinal products authorized in the European Union are subjects of constant drug-safety monitoring processes. It is organized in a pharmacovigilance system that is designed to protect human health and life by the detection, analysis and prevention of adverse drug reactions (ADRs) and other drug-related problems. The main role of the aforementioned system is to collect and analyze adverse drug reaction reports. Legislation introduced several years ago allowed patients, their legal representatives and caregivers to report adverse drug reactions, which caused them to be an additional source of safety data. This paper presents the analysis of EudraVigilance data related to adverse drug reactions provided by patients, their representatives, as well as those obtained from healthcare professionals related to medicines which belong to M01A anti-inflammatory and antirheumatic products, a non-steroid group. The objective of the study was to identify the changes in the number and structure of adverse reaction reporting after the introduction of pharmacovigilance (PV) obligations in EU. A review of scientific literature was also conducted to assess the differences in adverse reactions reported by patients or their representatives and by healthcare professionals. We also identified other factors which, according to literature review, influenced the number of adverse reaction reports provided by patients. Analysis of data collected from the EudraVigilance showed that from 2011 to 2013 the number of reports made by patients and their caregivers increased by approx. 24 percentage points, and then, from 2014, it constituted around 30% of the total of reported reactions every year, so patient reporting is an important part of pharmacovigilance system and a source of drugs’ safety information throughout their use in healthcare practice. Additionally, there was no interrelationship between the seriousness of reported adverse reactions and the overall number of patient reports when compared to reports form healthcare professionals.

Five-year outcomes of stereotactic body radiation therapy (SBRT) for prostate cancer: the largest experience in China

Objective To evaluate the efficacy and safety of SBRT for localized prostate cancer (PCa) with CyberKnife in China. Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China. Methods In this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray Inc., Sunnyvale, USA) from October 2012 to July 2019. Follow-up was performed every 3 months for efficacy and toxicity evaluation. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, respectively. Factors predictive of bPFS were identified with COX regression analysis. Results 133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of NCCN risk classification) with a median age of 76 years (range 54–87 years) received SBRT. The median dose was 36.25 Gy (range 34–37.5 Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6%, respectively. Urinary symptoms were all alleviated after SBRT. All patients tolerated SBRT with 1 (0.8%) patient reporting grade-3 acute and 1 (0.8%) patient reporting grade-3 late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis. Conclusion SBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.

Digitalization of adverse event management in oncology to improve treatment outcome—A prospective study protocol

The occurrence of adverse events frequently accompanies tumor treatments. Side effects should be detected and treated as soon as possible to maintain the best possible treatment outcome. Besides the standard reporting system Common Terminology Criteria for Adverse Events (CTCAE), physicians have recognized the potential of patient-reporting systems. These are based on a more subjective description of current patient reporting symptoms. Patient-reported symptoms are essential to define the impact of a given treatment on the quality of life and the patient’s wellbeing. They also act against an underreporting of side effects which are paramount to define the actual value of a treatment for the individual patient. Here, we present a study protocol for a clinical trial that assesses the potential of a smartphone application for CTCAE conform symptom reporting and tracking that is adjusted to the standard clinical reporting system rather than symptom oriented descriptive trial tools. The presented study will be implemented in two parts, both lasting over six months. The first part will assess the feasibility of the application with 30 patients non-randomly divided into three equally-sized age groups (<55years, 55-75years, >75years). In the second part 36 other patients will be randomly assigned to two groups, one reporting using the smartphone and one not. This prospective second part will compare the impact of smartphone reported adverse events regarding applied therapy doses and quality of life to those of patients receiving standard care. We aim for early detection and treatment of adverse events in oncological treatment to improve patients’ safety and outcomes. For this purpose, we will capture frequent adverse events of chemotherapies, immunotherapies, or other targeted therapies with our smartphone application. The presented trial is registered at the U.S. National Library of Medicine ClinicalTrials.gov (NCT04493450) on July 30, 2020.

From the ground up: recognising risk of frailty syndromes and functional decline through foot examination

Foot pathologies in older adults are associated with falls and complications such as amputations and ulcers. We report a case of an older man who presented to the geriatric medicine outpatient clinic. History taking revealed a fall, recent episode of delirium and decline in functional status with the patient reporting he was no longer able to cut his own toenails. Medical history included hypothyroidism, depression and hearing impairment. Physical examination detected very long, thickened toenails with bilateral bony deformities of the foot. Additionally, he had borderline slow gait speed and had difficulty completing a chair stand. Inability to maintain foot care suggested an early insight into a deterioration of overall function and emergence of frailty. An interprofessional team approach to the patient’s care included a medication review, referrals to podiatry, orthotics, physiotherapy and occupational therapy. His toenails were debrided and orthopaedic shoes were prescribed with no further falls.

Active Extraction of Experience of Adverse Drug Reactions in Children

OBJECTIVE Safety information regarding the use of medication, over-the-counter drugs, and supplements for Japanese children is scarce. The aim of this study was to clarify adverse drug reaction (ADR) experiences in children and consider the method to collect ADRs efficiently. METHODS We conducted a questionnaire survey regarding the ADR experiences of 20,412 children who were attending a preschool or kindergarten in the cities of Warabi and Toda, Saitama Prefecture, in May 2013. RESULTS Responses were received from the guardians of 15,076 children (49.5% girls; 8.2 ± 3.5 yr). A total of 196 guardians (1.3%) responded that their children had experienced ADRs. Among them, a total of 243 suspected drugs and 284 ADRs were reported. Of the 243 suspected drugs, 2.5% were associated with a vaccine. The most frequently reported medication, reaction, and “medication–reaction pair” were antibacterials for systemic use, rash, and “antibacterials for systemic use and rash,” respectively. CONCLUSIONS In this study, we clarified that there were many potential ADRs among children, but all “medication–reaction pairs” reported were consistent with adverse events reported in the clinical trials available in the prescribing information of each medication. This study provides data respective to the frequency of these adverse events in the general pediatric population. Additional education is needed to enlighten guardians of the importance to report ADRs through the Direct Patient Reporting System.

COVID-19 Dysautonomia

Objective: To report a case series of dysautonomia associated with COVID-19 infection.Methods: This is a retrospective review of patients evaluated in the autonomic clinic at our institution with suspected signs and symptoms of dysautonomia who underwent formal evaluation, including autonomic testing.Results: Six patients were identified with signs and symptoms suggestive of dysautonomia who underwent autonomic testing. All patients had symptoms typical of COVID-19 infection, though none were hospitalized for these or other symptoms. All patients reported symptoms of postural lightheadedness and near-syncope, fatigue, and activity intolerance. Five patients reported the onset of autonomic symptoms concomitant with other COVID-19 symptoms, with the other patient reporting symptom onset 6 weeks following initial COVID-19 symptoms. Autonomic testing demonstrated an excessive postural tachycardia in 4 patients, a hypertensive response with head-up tilt in 3 patients, orthostatic hypotension in 1 patient, and sudomotor impairment in 1 of the patients with excessive postural tachycardia.Conclusions: We present clinical features and results of autonomic testing in 6 patients with a history COVID-19 infection. While all patients reported typical features of orthostatic intolerance, fatigue, and activity intolerance, the results of autonomic testing were heterogenous, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.

Effect of Health Care Providers’ Focused Discussion and Proactive Education About Relapse Management on Patient Reporting of Multiple Sclerosis Relapse

Background: Treatments for multiple sclerosis (MS) relapse include intravenous corticosteroids and repository corticotropin injection. Despite available treatment, in the Multiple Sclerosis in America 2017 survey, only 47% of patients reported always/often contacting their MS health care provider (HCP) during relapse. In this study, the Multiple Sclerosis in America 2017 survey participants who received intravenous corticosteroids or repository corticotropin injection for treatment of past relapses completed a follow-up survey to understand how patients characterize relapse severity and to explore predictors of patients contacting their HCP during a relapse. Methods: Patients were18 years and older, diagnosed as having MS by an HCP, and currently using disease-modifying therapy. Patients completed an online survey assessing relapse characteristics and interactions with the HCP treating the patient’s MS. Regression analysis identified predictors of patients contacting their HCP during relapse. Results: Mean age of the 126 respondents was 49.2 years, 81.0% were female, and most (80.2%) had one or more relapses in the past 2 years. Patients estimated that 38.3% of their relapses were mild; 45.1%, moderate; and 16.6%, severe. Number and frequency of symptoms increased with relapse severity. Less than half (46.0%) reported they were extremely likely to contact their HCP during a relapse. The best predictors of being likely to contact the HCP during relapse were the HCP having previously discussed the importance of immediately communicating a relapse and patients’ willingness to accept the HCP’s recommendation for relapse treatment. Conclusions: Findings highlight the importance of HCPs’ advance discussions with patients with MS regarding relapse management to increase the likelihood patients will contact their HCP during relapse.

Adverse Drug Reaction Reporting by Patients in 12 European Countries

Patients who report suspected adverse drug reactions (ADRs) help minimize drug safety risks and bolster the pharmacovigilance system. The aim of this study was to examine the contribution of patients to pharmacovigilance and compare the tools used to promote patient reporting in European countries that implemented this reporting type in 2012–2013. A web-based questionnaire was sent to the national competent authorities (NCAs) of the European countries. The received answers were systematized and compared using statistical analysis. The performed statistical analysis demonstrated that changes in the number of received ADR reports increased significantly in each country during the analyzed period. These changes were significantly different in Ireland and Finland from those in the other reviewed countries. The common source of information on direct patient reporting was the country’s NCA website. Other sources used were social media pages, leaflets, and posters. This is the first study on patient reporting schemes implemented after the significant reform of the European regulatory system for pharmacovigilance. However, some countries did not actively promote their patient reporting schemes. Our findings indicate that countries with minimal experience in pharmacovigilance systems that include direct patient reporting should organize comprehensive campaigns on ADR reporting.