Safety cohort studies

Phase IV clinical trials and prospective observational cohort studies have been criticised as no more than promotional devices used by aggressive pharmaceutical companies. The fact that misuse has sometimes happened should not be allowed to obscure the greatly more important needs of safety evaluation and the further development of new and improved therapies. A set of guidelines has been published in the United Kingdom which are specifically intended to provide the high standards of study design and methodology necessary for observational cohort studies. It is to be hoped that similar procedures will be adopted internationally. 

A 2004 report by the Institute of Medicine s Immunization Safety Review Committee concluded that available evidence favored rejection of a causal relation between thimerosal-containing vaccines and autism. In like manner, a recent retrospective cohort study conducted by the CDC did not support a causal association between early prenatal or postnatal exposure to mercury from thimerosal-containing vaccines and neuropsychological functioning later in childhood. 

Krum H, Schlaich M, Whitboum P, et al. Catheter-based renal sympathetic denervation for resistant hypertension a multiplecentre safety and proof-of-principle cohort study. Lancet. 2009 373 1275-1281. 

Mackay, F., Dunn, N., Wilton, L., Pearce, G., Freemantle, S., Mann, R. (1997). A comparison of fluvoxamine, fluoxetine, sertraline, and paroxetine examined by observational cohort studies. Pharmacoepidemiology and Drug Safety, 6, 235-246. 

Tucker AP, Lai C, Nadeson R, Goodchild CS. Intrathecal midazolam I A cohort study investigating safety. Anesth Analg 2004 98 1512-20. 

Artemisinin derivatives have been studied in 461 pregnant women in a prospective cohort study in Thailand over 8 years (33). Oral artesunate monotherapy was associated with a treatment failure rate of 6.6%. Artesunate and artemether were well tolerated. The rates of abortions (including 44 first-trimester exposures), stillbirths, or congenital abnormalities were 4.8%, 1.58%, and 0.8% respectively, and were not significantly different from pregnant controls. These results are reassuring, but further information is needed before the safety of artesunate in pregnancy can be confirmed. 

Irl C, Hasford J. Assessing the safety of drugs in pregnancy the role of prospective cohort studies. Drug Saf 2000 22(3) 169-77. 

Wager E, Tooley PJ, Pearce GL, Wilton LV, Mann RD. A comparison of two cohort studies evaluating the safety of cisapride Prescription-Event Monitoring and a large phase PV study. Eur J Chn Pharmacol 1997 52(2) 87-94. 

A critical review of observational cohort studies conducted by or on behalf of pharmaceutical companies in the UK drew attention to a number of deficiencies in study design which, in certain cases, limited the value of the study. The authors, from the Medicines Control Agency and the Committee on Safety of Medicines, were motivated by the wish to improve the standard of postmarketing cohort studies, but they failed to distinguish... 

Other critics state that EBM considers randomized, controlled trials (RCTs) as the only evidence to be used in clinical decision making. AcmaUy, EBM seeks the best existing evidence from basic science to clinical research with which to inform clinical decision. For example, a decision about the accuracy of a diagnostic test is best informed by evidence from a cross-sectional study, not an RCT. A cohort study, not an RCT, best answers a question about prognosis. However, in selecting a treatment, the randomized trial is the best study design to provide the most accurate estimate of treatment efficacy and safety. 

Although randomized, controlled trials form the basis for some of the most reliable assessments of drug safety, pregnant women usually are not eligible for participation in clinical trials. Other types of data often are used to estimate the risk associated with medication use during pregnancy, such as animal studies, case reports, case-control studies, prospective cohort studies, historical cohort studies, and voluntary reporting systems. 

Gallo M, Au W, Koren G. The safety of echinacea use during pregnancy a prospective controlled cohort study. Teratology 1998 57 283. 

The objectives of the Phase IV program (see Tables 12.1 and 12.2) include further safety evaluation, comparative safety and efficacy vs. other products, discovery of new indications, and market expansion. Phase IV trials are not restricted to randomized, double-blind, placebo-controlled trials, but may include other study formats, such as open-label trials and case control and cohort studies. 

Lynch TJ et al. Preliminary treatment patterns and safety outcomes for non-small cell lung cancer (NSCLQ from ARIES, a bevadzumab treatment observational cohort study (OCS). Journal of Clinical Oncology (Meeting Abstracts) 2008 26 8077. 

One of the largest and most recent observational studies of Afib is the ATRIA-1 cohort study at Kaiser Permanente Northern California (KPNC). This cohort comprised 13,559 individuals who were members of KPNC with a diagnosis of Afib during years 1996-2003. These individuals were followed longitudinally for comorbidities, lab values, warfarin treatment, and stroke and death outcomes. The effectiveness of warfarin in reducing the risk of stroke or death was recently addressed in Brooks et al. (2013). The safety analysis in this chapter focuses on the estimation of the causal effect of warfarin on the probability of nonstroke death within the first year of follow-up. 

Paul M, Bishara J, Levcovich A, Chowers M, Goldberg E, Singer P, Lev S, Leon P, Raskin M, Yahav D, Leibovici L. Effectiveness and safety of colistin prospective comparative cohort study. J Antimicrob Chemother 2010 65(5) 1019-27. 

Patomo E, Everett BM, Goldfine AB et al (2016) Compeuative cardiovascular safety of glucagon-Uke peptide-1 receptor agonists versus other antidiabetic drugs in routine care a cohort study. Diabetes Obes Metab. [Epub ahead of print]... 

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