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BMC Medicine Feb 2016There have been no studies of the patterns of post-marketing withdrawals of medicinal products to which adverse reactions have been attributed. We identified medicinal... (Review)
Review
BACKGROUND
There have been no studies of the patterns of post-marketing withdrawals of medicinal products to which adverse reactions have been attributed. We identified medicinal products that were withdrawn because of adverse drug reactions, examined the evidence to support such withdrawals, and explored the pattern of withdrawals across countries.
METHODS
We searched PubMed, Google Scholar, the WHO's database of drugs, the websites of drug regulatory authorities, and textbooks. We included medicinal products withdrawn between 1950 and 2014 and assessed the levels of evidence used in making withdrawal decisions using the criteria of the Oxford Centre for Evidence Based Medicine.
RESULTS
We identified 462 medicinal products that were withdrawn from the market between 1953 and 2013, the most common reason being hepatotoxicity. The supporting evidence in 72 % of cases consisted of anecdotal reports. Only 43 (9.34 %) drugs were withdrawn worldwide and 179 (39 %) were withdrawn in one country only. Withdrawal was significantly less likely in Africa than in other continents (Europe, the Americas, Asia, and Australasia and Oceania). The median interval between the first reported adverse reaction and the year of first withdrawal was 6 years (IQR, 1-15) and the interval did not consistently shorten over time.
CONCLUSION
There are discrepancies in the patterns of withdrawal of medicinal products from the market when adverse reactions are suspected, and withdrawals are inconsistent across countries. Greater co-ordination among drug regulatory authorities and increased transparency in reporting suspected adverse drug reactions would help improve current decision-making processes.
Topics: Adverse Drug Reaction Reporting Systems; Africa; Americas; Asia; Australasia; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Europe; Evidence-Based Medicine; Humans; Oceania; Publications; Safety-Based Drug Withdrawals
PubMed: 26843061
DOI: 10.1186/s12916-016-0553-2 -
Tobacco Regulatory Science Oct 2016In this paper we synthesize the evidence from eye tracking research in tobacco control to inform tobacco regulatory strategies and tobacco communication campaigns.
OBJECTIVE
In this paper we synthesize the evidence from eye tracking research in tobacco control to inform tobacco regulatory strategies and tobacco communication campaigns.
METHODS
We systematically searched 11 databases for studies that reported eye tracking outcomes in regards to tobacco regulation and communication. Two coders independently reviewed studies for inclusion and abstracted study characteristics and findings.
RESULTS
Eighteen studies met full criteria for inclusion. Eye tracking studies on health warnings consistently showed these warnings often were ignored, though eye tracking demonstrated that novel warnings, graphic warnings, and plain packaging can increase attention toward warnings. Eye tracking also revealed that greater visual attention to warnings on advertisements and packages consistently was associated with cognitive processing as measured by warning recall.
CONCLUSIONS
Eye tracking is a valid indicator of attention, cognitive processing, and memory. The use of this technology in tobacco control research complements existing methods in tobacco regulatory and communication science; it also can be used to examine the effects of health warnings and other tobacco product communications on consumer behavior in experimental settings prior to the implementation of novel health communication policies. However, the utility of eye tracking will be enhanced by the standardization of methodology and reporting metrics.
PubMed: 27668270
DOI: 10.18001/TRS.2.4.9 -
The Cochrane Database of Systematic... Oct 2014Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammatory pain and swelling in inflammatory bowel disease (IBD) patients with rheumatological... (Review)
Review
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammatory pain and swelling in inflammatory bowel disease (IBD) patients with rheumatological manifestations. While these drugs effectively reduce musculoskeletal pain and stiffness, long-term use is limited by gastrointestinal (GI) adverse effects (AEs) and disease exacerbation. As an alternative to NSAIDs, selective cyclooxygenase 2 (COX-2) inhibitors were developed to improve GI safety and tolerability. COX-2 inhibitors include drugs such as celecoxib, rofecoxib, valdecoxib, etoricoxib, and lumiracoxib. Rofecoxib and valdecoxib have been withdrawn from the market worldwide due to safety concerns (most importantly for cardiovascular adverse events) and lumiracoxib has been withdrawn in many countries due to liver toxicity. However, celecoxib and etoricoxib continue to be available for use in many countries. Several studies have examined whether COX-2 inhibitors can be safely used for the treatment of rheumatological manifestations of IBD with inconsistent results. Some investigators report acceptable safety profiles associated with these drugs while others found that COX-2 inhibitors are associated with high rates of disease exacerbation.
OBJECTIVES
The objective of this systematic review was to evaluate the tolerability and safety of COX-2 inhibitors used for the treatment of rheumatological manifestations of IBD.
SEARCH METHODS
We searched the following databases from inception to 19 September 2013: PubMed, EMBASE, MEDLINE and CENTRAL. The search was not limited by language. Additional trials were identified by manually searching the reference lists of relevant papers and conference proceedings and through correspondence with experts and pharmaceutical companies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that compared COX-2 inhibitors to placebo were considered for inclusion. Participants were adult patients with IBD presenting with rheumatological manifestations of at least two weeks duration.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial eligibility and extracted data. Methodological quality was assessed using the Cochrane risk of bias tool. The primary outcome measure was the proportion of patients with disease exacerbation as defined by the included studies. Secondary outcomes included GI adverse effects, renal toxicity, cardiovascular and thrombotic events. Data were analysed on an intention-to-treat basis where patients with missing final outcomes were assumed to have had an exacerbation of IBD. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. The overall quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS
There were no RCTs that assessed the tolerability or safety of the withdrawn COX-2 inhibitors rofecoxib, valdecoxib, or lumiracoxib. Two RCTs (n = 381 IBD patients with rheumatological manifestations) were included in the review. One study (n = 159) compared etoricoxib (60 to 120 mg/day) to placebo in IBD patients with quiescent or active ulcerative colitis or Crohn's disease. The other study (n = 222) compared celecoxib (200 mg twice daily) to placebo in patients with quiescent ulcerative colitis. Both studies were judged to be at low risk of bias. The two included studies were not pooled for meta-analysis due to differences in patient populations and treatment duration. There was no statistically significant difference in exacerbation of IBD between etoricoxib and placebo. After 12 weeks of treatment the IBD exacerbation rate was 17% (14/82) in the etoricoxib group compared to 19% (15/77) in the placebo group (RR 0.88, 95% CI 0.45 to 1.69). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (29 events). There was no statistically significant difference in exacerbation of ulcerative colitis between celecoxib and placebo. After two weeks of treatment 4% (5/112) of celecoxib patients experienced an exacerbation of ulcerative colitis compared to 6% (7/110) of patients in the placebo group (RR 0.70, 95% CI 0.23 to 2.14). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (12 events). The study comparing etoricoxib to placebo documented but did not report on AEs. The proportion of patients who experienced AEs was similar in the celecoxib and placebo groups (21% and 17%, respectively, P > 0.20). No patients in either group died or experienced serious adverse events. Eleven percent of patients in the celecoxib and placebo groups experienced GI AEs (RR 0.97, 95% CI 0.46 to 2.07). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (24 events). GI AEs led to premature withdrawal from the study in 3% of patients in celecoxib and placebo groups respectively. GI AEs included increased stool frequency, rectal bleeding, and inflamed mucosa. No patients experienced any cardiovascular adverse events. Renal toxicity or thrombotic AEs were not reported.
AUTHORS' CONCLUSIONS
The results for disease exacerbation and AEs between the COX-2 inhibitors celecoxib and etoricoxib and placebo were uncertain. Thus no definitive conclusions regarding the tolerability and safety of the short term use of celecoxib and etoricoxib in patients with IBD can be drawn. The two included studies suggest that celecoxib and etoricoxib do not exacerbate IBD symptoms. However, it should be noted that both studies had relatively small sample sizes and short follow-up durations. Clinicians need to continue to weigh the risks and benefits of these drugs when treating patients IBD patients with rheumatological manifestations in order to avoid disease exacerbation and other adverse effects. Further RCTs are needed to determine the tolerability and safety of celecoxib and etoricoxib in these patients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Colitis, Ulcerative; Crohn Disease; Cyclooxygenase 2 Inhibitors; Diclofenac; Etoricoxib; Humans; Isoxazoles; Lactones; Pyrazoles; Pyridines; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Sulfonamides; Sulfones
PubMed: 25340915
DOI: 10.1002/14651858.CD007744.pub2