International Journal of Risk & Safety in Medicine - Volume 28, issue 1

Authors: Simonsen, Anders Lykkemark | Danborg, Pia Brandt | Gøtzsche, Peter Christian

Article Type: Review Article

Abstract: BACKGROUND: Sexual dysfunction is a common adverse effect of selective serotonin reuptake inhibitors (SSRIs) and there is a concern that the sexual harms might persist after discontinuation of therapy. OBJECTIVE: To assess whether the use of SSRIs in animals can lead to persistent sexual dysfunction. METHODS: Systematic review of animal studies measuring sexual behaviour after end of treatment with SSRIs or serotonin norepinephrine reuptake inhibitors. DATA SOURCES: We searched PubMed and EMBASE. RESULTS: We included 14 studies. The general quality of the studies was poor. Only four studies reported use of randomisation …and none mentioned allocation concealment. All studies used placebo and were therefore blinded. For rats exposed to SSRIs compared with those exposed to placebo, we found a higher risk of no mounting behaviour (RR = 0.73; 95% CI = 0.62–0.86), no intromission behaviour (RR = 0.74; 95% CI = 0.60–0.92) and no ejaculation behaviour (RR = 0.49, 95% CI = 0.24–1.00). CONCLUSION: Our results showed substantial and lasting effects on sexual behaviour in rats after exposure to an SSRI early in life on important sexual outcomes. Show more

Keywords: Selective serotonin reuptake inhibitors (SSRIs), long lasting harm, permanent sexual dysfunction, animal studies, systematic review

DOI: 10.3233/JRS-160668

Citation: International Journal of Risk & Safety in Medicine, vol. 28, no. 1, pp. 1-12, 2016

Authors: Awodele, Olufunsho | Ibrahim, Ali | Orhii, Paul

Article Type: Research Article

Abstract: BACKGROUND: Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank. OBJECTIVE: Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. METHODS: A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 …and the data were analyzed using SPSS version 17. RESULTS: Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia. CONCLUSION: More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals. Show more

Keywords: Signals, ADRs, Pharmacovigilance, NAFDAC, antiretroviral agents

DOI: 10.3233/JRS-160669

Citation: International Journal of Risk & Safety in Medicine, vol. 28, no. 1, pp. 13-23, 2016

Authors: Peymani, Payam | Tabrizi, Reza | Afifi, Saba | Namazi, Soha | Heydari, Seyed Taghi | Shirazi, Mohammad Khabaz | Nouraei, Hasti | Sadeghi, Elham | Lankarani, Kamran B. | Maharlouei, Najmeh

Article Type: Research Article

Abstract: BACKGROUND: An adverse drug reaction (ADRs) is linked with the use of medications and unpredictable negative consequences. The Iranian Pharmacovigilance center (IPC) has reported that the rate of ADR is very low. OBJECTIVE: Thus, this study was performed to find the reasons for this under-reporting, and investigate the level of knowledge, attitude and practice (KAP) of General Practitioners (GPs) about spontaneous reporting system in Shiraz. METHODS: The present cross-sectional study was conducted on 350 general practitioners (GPs) working in Shiraz, Iran from Oct 2014 to March 2015. A semi-structured questionnaire was used which included demographic features, …and evaluated KAPs of GPs regarding ADRs, Pharmacovigilance, and yellow card reporting. Statistical analysis was done by descriptive and analytical statistics (frequency, Mean±SD, Student t -test, Chi-square) using SPSS version 16. RESULTS: Of 350 (95.1%) GPs, 333 completed the questionnaire. The respondents aged from 26 to76 years, of whom 176 (52.9%) were males with mean age 39.6±8.8 SD years. In regard to work place, 85 (25.5%) had their own office, and 112 (33.7%), 101 (30.9%), and 35 (10.5%) worked in private hospitals, in governmental hospitals, and in more than one place, respectively. Work experience mean was 13.3±8.2SD years and median was 12 years (range 1–50 years). Although, less than half of the participants (n  = 151; 45.3%) described ADR correctly, 215 (64.6%) respondents claimed that they were not familiar with physician’s responsibility regarding ADR reporting. Overall, few of the participants were aware of the steps in either ADR reporting or using Yellow Card System. On the whole, 100 (30%) respondents achieved acceptable knowledge score, while the median score was 9 out of 14 and minimum and maximum being 5 and 14, respectively. CONCLUSIONS: The physicians in Shiraz have poor knowledge of the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude regarding ADRs reporting system. National Pharmacovigilance center should play a more active role in improving physicians’ adherence to the ADRs reporting systems and the comprehensive educational pack can be used in local and national meetings. The main factor for low ADR reporting rates is lack of information about ADRs and how to report an ADR. Otherwise, obligatory education and training courses should be designed for general practitioners on reporting ADRs during and after graduation. Show more

Keywords: General practitioners, knowledge, attitude, practice, adverse drug reaction, reporting, Iran

DOI: 10.3233/JRS-160670

Citation: International Journal of Risk & Safety in Medicine, vol. 28, no. 1, pp. 25-31, 2016

Authors: Jureidini, Jon N. | Amsterdam, Jay D. | McHenry, Leemon B.

Article Type: Research Article

Abstract: OBJECTIVE: Deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States. METHODS: Approximately 750 documents from the Celexa and Lexapro Marketing and Sales Practices Litigation : Master Docket 09-MD-2067-(NMG) were deconstructed. RESULTS: The published article contained efficacy and safety data inconsistent with the protocol criteria. Procedural deviations went unreported imparting statistical significance to the primary outcome, and an implausible effect size was claimed; positive post hoc measures were introduced and negative secondary outcomes were not reported; and adverse events …were misleadingly analysed. Manuscript drafts were prepared by company employees and outside ghostwriters with academic researchers solicited as ‘authors’. CONCLUSION: Deconstruction of court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety. Show more

Keywords: Citalopram, depression, escitalopram, FDA, ghostwriting, key-opinion-leaders, psychiatric litigation, research misconduct, SSRI antidepressants

DOI: 10.3233/JRS-160671

Citation: International Journal of Risk & Safety in Medicine, vol. 28, no. 1, pp. 33-43, 2016

Authors: dos Reis, Camila | Teixo, Ricardo | Mendes, Fernando | Cruz, Rui Santos

Article Type: Review Article

Abstract: INTRODUCTION: By definition, biosimilars are similar to a biological reference that has already received marketing authorization for biologic drugs. The purpose of biosimilars is reducing costs, thus increasing access to this treatment, however, the concerns of health professionals and users refer to the fact that to reduce costs will not neglecting the quality, effectiveness and especially security. OBJECTIVE: The aim of this study is then to assess the degree of similarity between the biosimilar and its reference biopharmaceuticals, trying to understand the production process, requirements necessary for approval, and its impact on the quality, safety, efficacy and costs. …METHODS: For the systematic review without meta-analysis, we researched articles to the b-on, Pubmed and Medscape to 2005–2014, and selected 23 articles that contributed to the verification of the objectives of this study. RESULTS: Several studies indicate that overall the biosimilar and biological reference showed no significant differences except those inherent to the production process, being the first susceptible to comparability tests demonstrating the similarity in terms of clinical efficacy and safety. CONCLUSION: Biosimilars will be increasingly present in the future as promising therapeutic arsenal and targeted therapy, however, issues related to immunogenicity, interchangeability, automatic substitution and extrapolation of indications should continue to be studied and debated. Show more

Keywords: Biosimilars, biologics, efficacy, safety, immunogenicity, interchangeability, extrapolation

DOI: 10.3233/JRS-160672

Citation: International Journal of Risk & Safety in Medicine, vol. 28, no. 1, pp. 45-60, 2016

Authors: Kapp, Marshall B.

Article Type: Letter

Abstract: The author describes his own negative series of encounters with the front office staff of a large specialty medical practice during a recent lengthy episode of significant medical distress. The author suggests several reasons, including legal risk management, that medical students should be exposed as part of their education to the interactions of patients with front office staffs (not just physicians) to get a fuller picture of patients’ actual experiences with the health care system.

Keywords: Office staff, medical education, patient relationships

DOI: 10.3233/JRS-160673

Citation: International Journal of Risk & Safety in Medicine, vol. 28, no. 1, pp. 61-64, 2016