Monitoring product safety in the postmarketing environment

Sharrar, Robert G.; Dieck, Gretchen S.

doi:10.1177/2042098613490780

Cited by 63 publications

(60 citation statements)

References 9 publications

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“…Selective enrollment of participants may also limit the generalizability in the postmarketing environment. Continuous safety surveillance is thus essential to ensure patient safety …”

Section: Introductionmentioning

confidence: 99%

Characteristics of drugs safety signals that predict safety related product information update

Insani

Păcurariu

Mantel‐Teeuwisse

et al. 2018

Pharmacoepidemiology and Drug

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PurposeInvestigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016.MethodsA comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI.ResultsMultivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources (adjusted odds ratio [OR] 7.8 95% CI [1.5, 40.1]); mechanistic plausibility of the drug‐event association (adjusted OR 3.9 95% CI [1.9, 8.0]); seriousness of the event (adjusted OR 4.2 95% CI [1.3, 13.9]); and age of drugs ≤5 years (adjusted OR 3.9 95% CI [1.2, 12.7]) were associated with the decision to change the PI (P < 0.05).ConclusionsThis study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates.

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“…Selective enrollment of participants may also limit the generalizability in the postmarketing environment. Continuous safety surveillance is thus essential to ensure patient safety …”

Section: Introductionmentioning

confidence: 99%

Characteristics of drugs safety signals that predict safety related product information update

Insani

Păcurariu

Mantel‐Teeuwisse

et al. 2018

Pharmacoepidemiology and Drug

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“…Information was lacking about relevant risk factors of stroke such as smoking, dyspepsia, the use of over-the-counter medicines, or presence of restricted mobility [24]. Regarding post-marketing data, some limitations should be mentioned [25]. Passive surveillance suffers from underreporting of AE which might affect the accuracy of the reporting rates.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous Interferon-β1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance

et al. 2018

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IntroductionPrevious studies suggest that multiple sclerosis (MS) patients have a greater stroke risk than the general population but there is limited evidence of stroke risk in patients receiving disease-modifying treatment. We assessed stroke risk in MS patients treated with subcutaneous interferon-β1a (sc IFN-β1a) using pooled data from clinical trials and post-marketing surveillance.MethodsSeventeen phase II–IV Merck KGaA-sponsored trials of sc IFN-β1a were assessed to estimate the stroke incidence rate (IR) and IR ratio (IRR) per 100 patient-years (PY), and associated 95% confidence intervals (CI). The association of treatment duration with stroke was assessed through a Cox model. IR, IRR, and hazard ratio (HR) were adjusted by age, sex, presence of any comorbidity, and MS duration. Individual case safety reports were retrieved from the Global Patient Safety Database. The reporting rates of stroke were calculated and classified as medically confirmed or non-medically confirmed according to the source of each report.ResultsIn 17 clinical trials, 4412 patients were treated with sc IFN-β1a for a total of 10,622 PY and 1055 patients with placebo for 2005 PY. The IR/100 PY (95% CI) of stroke was 0.025 (0.004, 0.150) in sc IFN-β1a patients and 0.051 (0.008, 0.349) in placebo patients. The IRR for sc IFN-β1a vs placebo was 0.486 (0.238, 0.995) and the HR was 0.496 (0.235, 1.043) for time to stroke-related event for sc IFN-β1a treatment at any dose compared with placebo. Among sc IFN-β1a patients, the IRR in those treated for < 2 years was 0.602 (0.159, 2.277) and for ≥ 2 years 0.469 (0.196, 1.124). Analysis of the safety database showed that the overall reporting rate for stroke was 13.286/10,000 PY.ConclusionSafety data from both clinical trial and post-marketing settings indicate that treatment with sc IFN-β1a does not increase stroke risk in patients with MS.FundingMerck KGaA, Darmstadt, Germany.

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“…A companion paper will discuss how a sponsor can monitor safety and assess risk postapproval [Sharrar and Dieck, 2013].…”

Section: Introductionmentioning

confidence: 99%

Preparing for safety issues following drug approval: pre-approval risk management considerations

Dieck¹,

Sharrar²

2013

Therapeutic Advances in Drug Safety

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Risk management plans and risk minimization plans as well as postapproval commitment studies are based on risks identified pre-approval that need to be further characterized or minimized in the postmarketing environment. Although the implementation of these activities are conducted in the postapproval arena, the design of the plans and studies as well as the development of effective postapproval tools and mitigation strategies should be carried out pre-approval. The pre-approval period also provides the opportunity to fully understand the treatment population that is included in the clinical trial program and to determine how the target population for the drug after approval may differ from the clinical trial patient population. When regulators or sponsors have expressed concerns about safety issues identified during clinical development, the result may be a postapproval commitment in the form of a registry or an observational safety study or, in the US, a Risk Evaluation and Mitigation Strategy (REMS) as a condition of approval. Specific examples are given for risk mitigation activities that can be conducted pre-approval.

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Monitoring product safety in the postmarketing environment

Cited by 63 publications

References 9 publications

Characteristics of drugs safety signals that predict safety related product information update

Characteristics of drugs safety signals that predict safety related product information update

Subcutaneous Interferon-β1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance

Preparing for safety issues following drug approval: pre-approval risk management considerations

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