Secondary use of randomized controlled trials to evaluate drug safety: a review of methodological considerations

Hammad, Tarek A.; Pinheiro, Simone P.; Neyarapally, George A.

doi:10.1177/1740774511419165

Cited by 38 publications

(63 citation statements)

References 93 publications

(107 reference statements)

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“…The exclusion of participants with symptomatic prostatic hyperplasia or bladder neck obstruction and moderate to severe renal impairment, the recruitment of a high proportion of short-acting anticholinergic users at baseline (approximately 50%) and during the trial (approximately 14% in both arms), and the high rate of loss to follow up of participants of approximately 40% in UPLIFT could have resulted in an inability to reliably ascertain systemic anticholinergic adverse effects. 'Depletion of susceptibles' is another possible explanation of the discrepant findings of adverse effects between earlier shortterm trials and longer-term studies [Hammad et al 2011]. Since the risk of urinary retention is most prominent soon after starting on anticholinergic drugs [Afonso et al 2011;Stephenson et al 2011;Martín-Merino et al 2009], patients most susceptible to drug-related bladder symptoms likely dropped out early on in UPLIFT, with only the healthier patients remaining in the intervention arm for long-term follow up.…”

Section: Discussionmentioning

confidence: 99%

Risk of acute urinary retention associated with inhaled anticholinergics in patients with chronic obstructive lung disease: systematic review

Loke

Singh

2013

Therapeutic Advances in Drug Safety

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BackgroundAcute urinary retention is a medical emergency which can be associated with serious complications. Previous studies have reported that the mortality rates in older men with precipitated acute urinary retention was double that of the general population [Armitage et al. 2007]. The mortality rates among men with acute urinary retention ranged from 9.5% in those aged between 45 and 54 years to 45.4% for men over 85 years of age [Armitage et al. 2007]. Hence, identification and avoidance of aetiological factors may have some impact in reducing risk of urinary retention and any associated medical complications.Acute urinary retention is typically related to the presence of prostatic disease. However, some drugs have been known to be associated with urinary retention, including antipsychotics, tricylic antidepressants, calcium channel antagonists and anticholinergic drugs [Verhamme et al. 2008].Risk of acute urinary retention associated with inhaled anticholinergics in patients with chronic obstructive lung disease: systematic review Yoon K. Loke and Sonal Singh Abstract: Inhaled anticholinergics (ipratropium bromide and tiotropium bromide) are widely used as maintenance treatment in chronic obstructive pulmonary disease. Previous studies have reported on their cardiovascular effects but relatively little is known about their effects on the bladder. Acute urinary retention is a medical emergency which can be associated with serious complications. Our objective was to evaluate the existing literature regarding the effects of inhaled anticholinergics on urinary retention among patients with chronic obstructive pulmonary disease. We searched PubMed and the United States Food and Drug Administration (FDA) adverse events database for case reports, observational studies, randomized controlled trials (or meta-analyses of such trials) that reported on the outcome of urinary retention with inhaled anticholinergics (ipratropium or tiotropium). We checked 27 published articles and identified relevant papers including two case reports, three pooled analyses, two observational studies and one randomized controlled trial. Two of the observational studies and a pooled analysis of randomized controlled trials reported a significant increase in the risk of acute urinary retention with inhaled anticholinergics. Older patients with benign prostatic hyperplasia seem to be at the highest risk of this adverse effect which tends to occur soon after treatment initiation. Although all the links in the chain have yet to be fully elucidated, the preponderance of evidence suggests the possibility of a causal relationship between inhaled anticholinergics and urinary retention. Clinicians should carefully balance these and other adverse effects of inhaled anticholinergics against their known symptomatic benefits on exacerbations, after eliciting patient preferences for various outcomes in a shared decisionmaking context.

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Section: Discussionmentioning

confidence: 99%

Risk of acute urinary retention associated with inhaled anticholinergics in patients with chronic obstructive lung disease: systematic review

Loke

Singh

2013

Therapeutic Advances in Drug Safety

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“…Regulatory agencies and clinicians rely on this information to understand the possible risks of a treatment decision. Incomplete AE reporting can lead to the underestimation of risk [2,3,9,11,19,20,27,28,32], potentially compromising regulatory approval and informed clinical use of treatments.…”

Section: Introductionmentioning

confidence: 98%

Adverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic review

Hunsinger¹,

Smith²,

Rothstein³

et al. 2014

Pain

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Assessment of treatment safety is 1 of the primary goals of clinical trials. Organizations and working groups have created reporting guidelines for adverse events (AEs). Previous research examining AE reporting for pharmacologic clinical trials of analgesics in major pain journals found many reporting inadequacies, suggesting that analgesic trials are not adhering to existing AE reporting guidelines. The present systematic review documented AE reporting in 3 main pain journals for nonpharmacologic, noninterventional (NP/NI) trials examining pain treatments. To broaden our pool of nonpharmacologic trials, we also included trials examining acupuncture, leech therapy, and noninvasive stimulation techniques (eg, transcutaneous electrical nerve stimulation). We documented AE reporting at 2 levels of specificity using coding manuals based on the Consolidated Standards of Reporting Trials (CONSORT) harms reporting standards and Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) AE reporting checklist. We identified a number of inadequacies in AE reporting across the 3 journals. For example, using the ACTTION coding manual, we found that less than one-half of the trials reported specific AE assessment methods; approximately one-third of the trials reported withdrawals due to AEs for each study arm; and about one-fourth of the trials reported all specific AEs. We also examined differences in AE reporting across several trial characteristics, finding that AE reporting was generally more detailed in trials with patients versus those using healthy volunteers undergoing experimentally evoked pain. These results suggest that investigators conducting and reporting NP/NI clinical trials are not adequately describing the assessment and occurrence of AEs.

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“…Concerns about epidemiological concepts such as external validity and generalizing use of research drugs have been raised in clinical trials (Hammad et al 2011). If women are not studied appropriately during the development of the drug in early Phases I and II of clinical trials, then how can the safety and efficacy of a particular compound be assessed with confidence for the general population?…”

Section: Limitations Of the Currents Status Of Clinical Research In Wmentioning

confidence: 99%

Considerations of Sex and Gender Differences in Preclinical and Clinical Trials

Raz

Miller

2012

Handbook of Experimental Pharmacology

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Women continue to be underrepresented in clinical trials, particularly in Phases I and II of experimental drug studies in spite of legislative guidelines in the USA, Canada, the European Union, Australia, and Japan requiring the inclusion of women in clinical trials. As such, women remain a vulnerable population subject to the adverse effects of pharmacological therapies. Thus, women experience higher rates of adverse drug reactions than do men and for women of reproductive age or who may be pregnant, therapeutic options may be limited. This chapter provides a brief history of inclusion of sex and gender as variables in clinical trials, summarizes governmental legislation for consideration of sex and gender in clinical trials and provides specific examples of drugs which have been withdrawn from the market because of side effects in women. Additional information related to sex and gender in preclinical testing, trial design, challenges to recruitment of women for clinical trials and statistical methods for analysis of data also is considered.

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Secondary use of randomized controlled trials to evaluate drug safety: a review of methodological considerations

Cited by 38 publications

References 93 publications

Risk of acute urinary retention associated with inhaled anticholinergics in patients with chronic obstructive lung disease: systematic review

Risk of acute urinary retention associated with inhaled anticholinergics in patients with chronic obstructive lung disease: systematic review

Adverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic review

Considerations of Sex and Gender Differences in Preclinical and Clinical Trials

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