International Journal of Risk & Safety in Medicine - Volume Pre-press, issue Pre-press

Authors: Pandey, Ekta | Paul, Sourabh B.

Article Type: Research Article

Abstract:  In an era which marks an exceptional phase of growth in science and technology, the acute disparities in access to healthcare still persist. So where on one hand scientific advancement in medicine aims at increasing life expectancy, on the other hand there are millions who are denied access to existing medicines. Patents on medicines also pose a significant barrier to access new drugs, especially in low and middle income countries which already suffer from poor health financing mechanisms. The patent laws were built on the assumption of incentivizing the innovators by rewarding them with the exclusive right to produce, sell …or market the innovation. The basic premise for granting patents was based on the thought that it would increase investment in research and development promoting dynamic gains through newer innovations. However, evidence found to support this justification is meager. So in a situation where the drug gap still persists and we aim to achieve sustainable development goals by 2030, this paper attempts to focus on understanding how compulsory licensing has been used in selected cases to alleviate the major legal and political barriers to access medicines. The methodology comprises of cross-country comparison of patent framework and compulsory licensing cases. The sample selected for study includes both developed as well as developing countries. The aim is to evaluate the policy approaches used by selected countries to grant compulsory licenses and to identify the best practices for evidence-based policy making on international issues related to pharmaceutical patents. In each case, a driving factor has been the international extension of patent laws through trade agreements; first bilaterally (US-Canada) and subsequently internationally (1995 Uruguay round, under which low- and middle-income countries were granted a grace period until 2005 to comply). Show more

DOI: 10.3233/JRS-195007

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-15, 2019

Authors: Gøtzsche, Peter C.

Article Type: Research Article

Abstract: BACKGROUND: The widespread use of psychiatric drugs does not appear to be evidence-based but seems to be driven mainly by commercial pressures. I studied whether two widely differing drug classes, antipsychotics and antidepressants, showed similar patterns in long-term usage. METHODS: I constructed usage curves over a ten-year period, from 2006 to 2016, based on data from Statistics Denmark. RESULTS: In 2006, a total of 110,235 patients deemed a prescription for an antipsychotic and 395,018 for an antidepressant, corresponding to 2.0% and 7.3% of the Danish population. Only 21,846 vs. 79,030 of these were first-time users (19.8% …vs. 20.0% ). The percentage of current users who redeemed a prescription for the same or a similar drug in each of the following years was remarkably similar for the two classes of drugs, and after ten years, it was 35% vs. 33%. Using the requirement that the patients identified in 2006 needed to redeem the prescription only once during the next ten years, 42% vs. 43% were taking a drug in 2016. This suggests that most patients identified at any given point in time as drug users continue taking such drugs for many years, with little or no interruption in drug intake. For first-time users, the drop in usage was much quicker. The percentage of first-time users who redeemed a prescription for the same or a similar drug in each of the following years fell to about one-third (29% vs. 36% ) already after two years. Using 2011 as the starting year yielded similar results. CONCLUSIONS: If we accept the evidence-based premises that antipsychotics and antidepressants do not have clinically relevant effects and that the patients dislike them, the data suggest massive overuse of the drugs, to a remarkably similar degree. We need to focus on helping patients withdraw slowly and safely from the drugs they are on instead of telling them that they need to stay on them. Show more

Keywords: Antipsychotics, antidepressants, usage

DOI: 10.3233/JRS-195060

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

Authors: Katyal, Jatinder | Arora, Ekta | Gupta, Yogendra Kumar

Article Type: Research Article

Abstract: BACKGROUND: Recent years have seen a surge in pharmacovigilance (PV) related activities in India. In the present study the impact of these initiatives on medical students from across the country was evaluated to identify their effectiveness, lacunae and arrive at remedial measures. METHODS: A cross-sectional, questionnaire based study was conducted. The survey questionnaire consisted of 28 multiple response items. The areas covered included subject knowledge (theoretical and practical), attitude and awareness towards pharmacovigilance. RESULTS: The survey participants (n  = 253) were from 71 medical colleges and 17 states across India. While 60% of the participants were familiar …with the term ‘Pharmacovigilance’, many could not distinguish side effect and adverse drug reaction. The majority was unaware that ‘Periodic Safety Update Report’ (PSURs) is a mandatory pharmacovigilance activity by the industry. 91% felt reporting is a useful practice and causes for under-reporting are a lack of awareness followed by attitude, misconceptions about what to report, fear of litigation and interestingly the least important is lack of time. However, most were reluctant to have reporting as mandatory tool; they would rather use it voluntary. CONCLUSION: In spite of collaborative and synchronized efforts by various agencies there is a need to further improve the PV milieu in India by confidence building exercises, imparting training on PV programme, updating of the current knowledge on PV and also sustaining motivation. Show more

Keywords: Pharmacovigilance, medicine safety, adverse drug reaction, medical students, India

DOI: 10.3233/JRS-195012

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Ivashchenko, D.V. | Buromskaya, N.I. | Savchenko, L.M. | Shevchenko, Yu.S. | Sychev, D.A.

Article Type: Research Article

Abstract: OBJECTIVE: To analyse the frequency, structure and risk factors of adverse drug effects in adolescents with acute psychotic episode by the methods of global triggers - Paediatric All-Cause Harm Measurement Tool (PACHMT) and Global Assessment of Paediatric Patient Safety Tool (GAPPS). PATIENTS AND METHODS: We used 151 completed case histories of patients who were admitted to a psychiatric hospital with acute psychotic episode. We applied Global Trigger Tool algorithm to each case retrospectively: we developed a special trigger list for psychiatric patients based on PACHMT, GAPPS and general Global Trigger Tool. We also calculated the Medical Appropriateness Index …(MAI) for each case. We applied trigger tool analysis for calculation of treatment safety parameters. Statistical analyses included Pearson’s Chi-square, Mann-Whitney U, and Kruskal-Walles tests. RESULTS: We identified a total of 261 triggers among 151 analysed cases, 51 of which were accompanied by adverse drug effects (ADEs) (overall positive prediction value = 19.54% ). The value of ADEs per 1000 bed days was 4.73, ADEs per 100 admissions was 33.77%. Extrapyramidal reactions to antipsychotics (58.8% ) were the most common ADEs, followed by an abrupt medication stop of one or more drugs due to ADEs (25.5% ). Significant predictors of antipsychotic-induced extrapyramidal symptoms were age, MAI score and total number of hospital admissions. CONCLUSION: We recommend three triggers, “Abrupt medication stop”, “Prescribing of extrapyramidal symptoms corrector”, and “Hospital readmission within 30 days”, with reasonable positive predictive value for incorporation into routine systems for patient safety monitoring in adolescents with an acute psychotic episode. Antipsychotic-induced extrapyramidal symptoms were more prevalent in older adolescents and patients with fewer lifetime hospital admissions. These patients need to be carefully monitored to ensure patient safety. Show more

Keywords: Drug safety, psychiatry, Global Trigger Tool, antipsychotics, safety, adolescents, GAPPS

DOI: 10.3233/JRS-195030

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Harasani, Klejda | Xhafaj, Delina | Qipo, Orgesa

Article Type: Research Article

Abstract: BACKGROUND: Prevalence of potentially inappropriate prescriptions (PIP) varies among community-dwelling patients and this difference partly depends on the methods used to evaluate improper use. OBJECTIVE: The aim of our study was to assess the prevalence and type of PIP among community-dwelling elderly as well as among middle-aged people by applying three different explicit tools – Ghent Older People’s Prescriptions community Pharmacy Screening (GheOP3 S) tool, The European Union Potentially Inappropriate Medications EU(7)-PIM list and PRescribing Optimally in Middle-aged People’s Treatments (PROMPT). METHODS: Cross-sectional study among community-dwelling patients in Tirana (Albania) from 1 March to 1 June …2018. Two community pharmacists reviewed the prescriptions independently. The PIP index and the mean number of PIP / patient was calculated. RESULTS: In total, 241 participants were included in the study. Among 142 elderly patients, 55.6 % and 54.2 % of them were prescribed at least one PIP, respectively according to the GheOP3 S tool and the EU7 PIM list. After applying PROMPT criteria, we found at least one PIP in 33.3 % of the middle-aged patients. The most commonly represented PIP drugs groups were cardiovascular drugs among older people and non-steroidal anti-inflammatory drugs among middle-aged people. Reminding and proposing the patient to undergo yearly influenza vaccination was the most common potentially prescribing omission. CONCLUSIONS: Prevalence of PIP is higher in elderly patients and slightly different according to the tool used for detection. However, PIP are also common in the middle-aged population. Show more

Keywords: Potentially inappropriate prescriptions, community-dwelling patients, prevalence, Albania ORCID 0000-0002-1877-6662

DOI: 10.3233/JRS-195052

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Danborg, P.B. | Gøtzsche, P.C.

Article Type: Research Article

Abstract: OBJECTIVE: To study the benefits and harms of antipsychotics in drug-naïve patients with psychosis. METHODS: This study is a systematic review and meta-analysis of placebo-controlled trials. Main outcome measures: Mortality, activities of daily living, quality of life, core psychiatric events, and relapse and recovery rates. Data sources: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), two trial registers and references in potentially eligible articles. Data extraction: Two researchers extracted data independently. The outcomes were planned to be meta-analysed using Review Manager based on a fixed effect model. RESULTS: Our searches resulted in 493 unique …records of which 447 were clearly not eligible. We read the full text of the 46 potentially eligible articles and found one eligible trial in drug-naïve patients, which was unreliable. It was a Chinese trial comparing olanzapine with placebo in 261 patients with first-episode schizophrenia. After 12 weeks, there was an extremely large difference favouring placebo, but the authors reported the opposite, that olanzapine was effective. CONCLUSIONS: The use of antipsychotics cannot be justified based on the evidence we currently have. Withdrawal effects in the placebo groups make existing placebo-controlled trials unreliable. Show more

Keywords: Antipsychotics, drug-naïve, first-episode, psychosis, schizophrenia

DOI: 10.3233/JRS-195063

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Sharma, Tarang | Guski, Louise Schow | Freund, Nanna | Meng, Dina Muscat | Gøtzsche, Peter C.

Article Type: Research Article

Abstract: Objective: To study the drop-out rates in trials of selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs). Methods: This study is a systematic review and meta-analysis of trials. The main outcome measure: Overall drop-out rate. Secondary outcomes were drop-outs due to adverse events and lack of effect. We obtained clinical study reports (CSRs) of five antidepressant drugs from the European Medicines Agency and the UK’s Medicines and Healthcare products Regulatory Agency. The eligibility criteria for selecting studies: double-blind randomised, placebo-controlled trials for any indication. Data extraction and analysis: The primary outcome was extracted by two researchers independently …and meta-analysed using the Mantel-Haenszel method (fixed effect model). The secondary outcomes were extracted by one researcher and checked by another. Sensitivity analyses were performed using Peto’s odds ratio and beta binomial methods, due to presence of null events, and by excluding unreliable trials. Results: We included 71 CSRs (67,319 pages) with information on 73 trials (11,057 patients on SSRI or SNRI drugs, and 7,369 on placebo). There were minor discrepancies within the CSRs when a modified intention to treat principle was used and patients lost to follow up early in the trial were not accounted for. Significantly more patients dropped out on active drug than on placebo, risk ratio 1.08 (95% CI 1.03 to 1.13), with no difference between adults and children/ adolescents, RR = 1.08 (1.03 to 1.13) and 1.07 (0.95 to 1.21), respectively. When three trials with a prior single-blind phase on active drug were removed, the difference was a risk ratio of 1.12 (1.07 to 1.18), whereas the result was the same after removal of three trials with fraudulent data or other issues with data validity, risk ratio 1.08 (1.03 to 1.13). There were more drop-outs due to adverse events on active drug than on placebo, risk ratio 2.63 (2.33 to 2.96). There were fewer drop-outs due to lack of effect, risk ratio 0.47 (0.43 to 0.53). However, this result is biased; when more people drop out due to adverse effects, fewer can drop out because of lack of effect. Conclusions: By using CSRs, we were able to demonstrate for the first time that more patients dropped out on active drug than on placebo. As it can be argued that the drop-out rate reflects the patients’ overall assessment of the balance between benefits and harms, our review adds to the growing concern that SSRIs and SNRIs might not have the desired effect. Our review also highlights the importance of using CSRs for undertaking reviews of drugs. Show more

Keywords: Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, drop-out rates, drug acceptability, drug tolerability, clinical study reports

DOI: 10.3233/JRS-195041

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-16, 2019

Authors: Okkenhaug, Arne | Tritter, Jonathan Q. | Myklebust, Tor Åge | Deilkås, Ellen T. | Meirik, Kathinka | Landstad, Bodil J.

Article Type: Research Article

Abstract: BACKGROUND: Patients treated in psychiatric care are exposed to the risk of adverse events, similar to patients treated in somatic health care. OBJECTIVES: In this article we report the findings of triggers associated with adverse events (AEs) identified by a version of the Global Trigger Tool – Psychiatry (GTT-P) adapted for Norwegian hospital-based psychiatric treatment. METHODS: The design was a retrospective analysis of a random sample of 240 patient records from a psychiatric clinic in one Norwegian hospital. Patient records were sampled from both inpatient and outpatient psychiatric clinics in hospitals serving the northern part of …the county of Trøndelag, Norway. RESULTS: Our analysis was based on the identification of 32 potential triggers of adverse events. Eighteen of the triggers were significantly related to adverse events. No adverse events were identified in patient records that did not also contain triggers included in the Global Trigger Tool. CONCLUSIONS: There is a clear relationship between the presence of triggers in a patient record and the likelihood of adverse events. Particularly relevant for psychiatric patients is ‘suffering’ as a trigger and this may also be relevant to somatic care and has implications for inclusion in the GTT-P. Show more

Keywords: Adverse events, mental health, patient safety, precipitating factors, psychiatry

DOI: 10.3233/JRS-190064

Citation: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-14, 2019