A decade of safety-related regulatory action in the Netherlands: a retrospective analysis of direct healthcare professional communications from 1999 to 2009.
Background: As pre-approval trials are inherently limited in assessing the complete benefit-risk profile of a new drug, serious safety issues may emerge once a drug gains widespread use after approval. Regulators face the dilemma of balancing timely market access with the need for complete data on r...
| Publicado en: | Drug Safety Vol. 33; no. 6; pp. 463 - 475 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
2010
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105206819&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105206819 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01145916 C5E jtl: Drug Safety issn: 01145916 maglogo: N pubinfo: dt: 2010 vid: 33 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105206819 53402842 NLM20486729 2010662607 10.2165/11532840-000000000-00000 NLM20486729 105206819 ppf: 463 ppct: 12 formats: tig: atl: A decade of safety-related regulatory action in the Netherlands: a retrospective analysis of direct healthcare professional communications from 1999 to 2009. aug: au: Mol PG Straus SM Piening S de Vries JT de Graeff PA Haaijer-Ruskamp FM Mol, Peter G M Straus, Sabine M J M Piening, Sigrid de Vries, Jonie T N de Graeff, Pieter A Haaijer-Ruskamp, Flora M affil: University Medical Center Groningen, Groningen, the Netherlands sug: subj: Drug and Narcotic Control Statistics and Numerical Data Drug and Narcotic Control Trends Drugs, Prescription Adverse Effects Product Recall Product Recall Trends Communication Human Netherlands Product Evaluation Statistics and Numerical Data Time Factors ab: Background: As pre-approval trials are inherently limited in assessing the complete benefit-risk profile of a new drug, serious safety issues may emerge once a drug gains widespread use after approval. Regulators face the dilemma of balancing timely market access with the need for complete data on risks. This challenge has led to a life-cycle approach but, so far, few data are available on post-approval safety issues requiring regulatory action.Objective: The aim of this study is to determine the frequency, timing and nature of safety issues that necessitated safety-related regulatory action in the form of a Direct Healthcare Professional Communication (DHPC) issued by pharmaceutical companies in collaboration with the Dutch Medicines Evaluation Board during the past decade.Methods: All DHPCs issued in the Netherlands from 1 January 1999 to 1 January 2009 were retrospectively collected from the national regulatory authorities. Elapsed time between the approval date and the issue of the DHPC was determined. Characteristics of the action including the nature of the safety issue (according to Medical Dictionary for Regulatory Activities [MedDRA] terminology), type of drug and procedural aspects of the regulatory action taken were reviewed. DHPC characteristics were tabulated and explorative non-parametric tests were performed to study the effect of safety issue, drug class, drug type, orphan drug and first-in-class status on elapsed time from approval to the DHPC.Results: 157 DHPCs were issued concerning 112 different active substances, approximately 9% (112/1200) of active substances available in the Netherlands in 2007. The number of DHPCs issued increased by 2.1 (95% CI 1.2, 3.1; p < 0.001) DHPCs per year over the past decade, reaching a total of 25 in 2008. The median time between approval and DHPC was 5.3 years (range 0.13-48 years). No significant trend in elapsed time to DHPC was observed in relation to the studied years (p = 0.06). One-third of all DHPCs were issued in the first 3 years after approval, but 27% (n = 43/157) of the DHPCs were issued 10 or more years after approval. Timing of DHPCs differed depending on safety issue, drug class, drug type and orphan drug status. DHPCs mostly concerned adverse events in the system organ class of 'cardiac disorders' (15%), 'injury, poisoning and procedural complications' (13%) and 'general disorders and administration site conditions' (10%). In ten cases the drug was eventually withdrawn. Withdrawal occurred a median duration of 2.4 years after registration (range of 1.5-48 years) and was most frequently due to cardiac disorders (including QT interval prolongation; four occasions) and hepatobiliary disorders (two occasions).Conclusions: In the past decade, the number of DHPCs has increased over time. This is likely caused by a multitude of factors: increased risk awareness by the public, media, regulators and other stakeholders; the type of drugs approved, such as orphan drugs and biologicals; and the regulatory process, including conditional approvals. The number of DHPCs may in the future increase further with the possibility of screening large epidemiological databases proactively for adverse drug events. Nine percent of all marketed drugs required a safety-related action. Regulatory action is taken shortly (<3 years) after market approval nearly as often as after intermediate (3-10 years) and long-term (>10 years) market exposure. These findings underline the need for risk management during the whole life cycle of a drug. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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