International Journal of Risk & Safety in Medicine - Volume 30, issue 4

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. 30, no. 4, pp. 193-201, 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. 30, no. 4, pp. 203-216, 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. 30, no. 4, pp. 217-232, 2019

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

Keywords: Compulsory license, intellectual property rights, TRIPS agreement, DOHA declaration, TRIPS flexibility

DOI: 10.3233/JRS-195007

Citation: International Journal of Risk & Safety in Medicine, vol. 30, no. 4, pp. 233-247, 2019