Clinical Trials—Collecting Safety Data and Establishing the Adverse Drug Reactions Profile

Talbot, John; Keisu, Marianne; Ståhle, Lars

doi:10.1002/9780470975053.ch4

Cited by 7 publications

(5 citation statements)

References 198 publications

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“…We acknowledge the hazards of multiple testing , without correction, but recognise the tensions between umbrella terms, which can hide true signals between specific anomalies and specific medicines, and narrow categories or rare outcomes yielding numbers too small for statistical comparisons[114,115]. A priori hypotheses[9,27,31,35,51] were tested without statistical adjustment, to limit misinterpretation (Table 3)[116].…”

Section: Discussionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

et al. 2016

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BackgroundHypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP).Methods and FindingsThree population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression.ConclusionThe additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care.

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Section: Discussionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

et al. 2016

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“…This was a feasibility study, without a comparator or “control” group, typical of adverse event research [ 74 ]. Low numbers precluded inferential analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Duration of follow-up was suboptimal, as in large trials of ADR initiatives [ 13 ], reflecting available resources. As in all uncontrolled adverse event studies, signs and symptoms may have been related to underlying conditions, concurrent therapy, or spontaneous events [ 74 ], and we cannot infer causation of the problems identified. However, to service users, amelioration may be more important than aetiology, and problem identification is a necessary prerequisite to management.…”

Section: Discussionmentioning

confidence: 99%

Medication Monitoring for People with Dementia in Care Homes: The Feasibility and Clinical Impact of Nurse-Led Monitoring

Jordan

Gabe

Newson

et al. 2014

The Scientific World Journal

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Objectives. People with dementia are susceptible to adverse effects of medicines. However, they are not always closely monitored. We explored (1) feasibility and (2) clinical impact of nurse-led medication monitoring. Design. Feasibility “before-and-after” intervention study. Setting. Three care homes in Wales. Participants. Eleven service users diagnosed with dementia, taking at least one antipsychotic, antidepressant, or antiepileptic medicine. Intervention. West Wales Adverse Drug Reaction (ADR) Profile for Mental Health Medicines. Outcome Measures. (1) Feasibility: recruitment, retention, and implementation. (2) Clinical impact: previously undocumented problems identified and ameliorated, as recorded in participants' records before and after introduction of the profile, and one month later. Results. Nurses recruited and retained 11 of 29 eligible service users. The profile took 20–25 minutes to implement, caused no harm, and supplemented usual care. Initially, the profile identified previously undocumented problems for all participants (mean 12.7 (SD 4.7)). One month later, some problems had been ameliorated (mean 4.9 (3.6)). Clinical gains included new prescriptions to manage pain (2 participants), psoriasis (1), Parkinsonian symptoms (1), rash (1), dose reduction of benzodiazepines (1), new care plans for oral hygiene, skin problems, and constipation. Conclusions. Participants benefited from structured nurse-led medication monitoring. Clinical trials of our ADR Profile are feasible and necessary.

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“…Primary care pharmacist questioning identified problems in 168/180 patients, for example, xerostomia, sweating, diarrhoea, constipation [ 112 ]. ADR reporting in clinical trials using standard questions and diary cards increased ADR reporting, for example, from 1.5–5.1% to 29–49% [ 113 ]. In USA primary care, 18% (394/2248) of patients reported ADRs to researchers, but only 3% (64) had previously had these documented [ 114 ]; incontinence and headache are among problems least likely to be documented [ 115 ].…”

Section: Regulatory Interventions To Modify Prescribing and Outcommentioning

confidence: 99%

Adverse Drug Reactions, Power, Harm Reduction, Regulation and the ADRe Profiles

et al. 2018

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The power and influence of healthcare systems comes largely from the ability to prescribe efficacious medicine. However, medicine can sometimes cause harm rather than bring benefits. Systematically checking patients for the adverse effects of medicines, as listed in manufacturers’ literature, would protect patients from iatrogenic harm, but this is rarely undertaken. We argue for the benefits of this approach using the example of the prescription of antipsychotics to older adults. Prescribing antipsychotics to control challenging behaviours associated with dementia is a controversial matter, and regulatory intervention is under discussion. Improved regulatory systems could protect against iatrogenic harm, such as over-sedation, falls, tremor, or drug-induced Parkinsonism. However, measuring the impact and outcomes of regulatory interventions has proved difficult, not least because there are rarely systematic records of all adverse effects of medicines. We indicate how regulatory initiatives to reduce antipsychotic prescribing can be supported by systematic monitoring and documentation of patients’ signs and symptoms of putative adverse drug reactions. Monitoring documentation then provides the rationale and support for professionals’ responses to identified problems. Longitudinal monitoring records would improve understanding of the impact and outcomes of adverse drug reactions (ADRs) on health and wellbeing, and the many costs of ADRs.

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Clinical Trials—Collecting Safety Data and Establishing the Adverse Drug Reactions Profile

Cited by 7 publications

References 198 publications

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Medication Monitoring for People with Dementia in Care Homes: The Feasibility and Clinical Impact of Nurse-Led Monitoring

Adverse Drug Reactions, Power, Harm Reduction, Regulation and the ADRe Profiles

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