Postmarketing Study Reports

Currently, the Annual Postmarketing Study Report should include the following ... 

The exception is the NDA/ANDA Postmarketing Study Reports, which are evolving and likely to become more structured and more closely scrutinized. Once those new guidelines are released, strict adherence to then-requirements will be mandatory, at the ultimate risk of a withdrawing of drug approval. 

Hypersensitivity reactions Serious hypersensitivity reactions have been rarely reported. One case of a life-threatening hypersensitivity reaction has been observed in a patient who received a single dose of sodium ferric gluconate complex in a postmarketing study. Three serious hypersensitivity reactions have been reported from the spontaneous reporting system. 

NDA requires manufacturers to submit product-labeling language, which describes the proper use, benefits, and risks of the product in question. FDA may also require, as a condition of approval of an NDA or BLA application, that postmarketing studies be conducted to monitor and confirm the safety and efficacy of a product as it is used more widely in clinical practice. In addition, all sponsors or manufacturers are required to monitor and report adverse effects, defined as health effects that may or may not be related to the drug in question. For vaccines, adverse events that occur after immunization must be reported to the Vaccine Adverse Event Reporting System. 

US Food and Drug Administration (USFDA). 2002. Report to Congress. Reports on Postmarketing Studies [FDAMA 130], Washington, DC FDA. 

Under the current final rule, those applicants with a commitment to conduct postmarketing studies must submit an annual report within 60 days of the anniversary of the product approval, and annually thereafter until notified by the Agency that either (a) the study commitment has been met or (b) the study is either no longer feasible or would not provide any additional useful data. 

In response to voluntary reports from physicians to the FDA or the manufacturer, the FDA has issued warnings, made label changes, required manufacturers to conduct postmarketing studies, and ordered product withdrawals that have ultimately prevented patient deaths and suffering. 

In 32 207 patients taking part in a short (1-4 weeks) postmarketing study of tolmetin, adverse effects occurred in 12%, and led to withdrawal in 3.6% (1). Tolerability was similar to that of naproxen, indometacin (SEDA-7, 114), and ibuprofen (SED-9, 152) (2). In another retrospective study in patients treated for 1 year or more with tolmetin, 64% reported generally mild transitory adverse effects. In controlled studies, about 10% of patients withdrew owing to adverse effects (3). In another study of 25 000 prescription records (4), tolmetin caused adverse... 

O Neill RT (1998) Biostatistical considerations in pharmacovigilance and pharmacoepidemiology Linking quantitative risk assessment in pre-market licensure application safety data, postmarket alert reports and formal epidemiological studies. Statistics in Medicine 17 1851-1858. 

Systematic reviews There has been a systematic review of adverse reactions to black cohosh as reported in 13 clinical trials, three postmarketing surveillance studies, four case series, and eight single case reports [25 ]. Three studies reported no serious adverse events. In one trial one of 21 patients had joint pain in the hands. Another trial reported... 

Studies in animals or humans or investigational or postmarketing reports, have shown fetal risk that dearly outweighs any possible benefit to the patient. 

LD Sasich, P Lurie, SM Wolfe. The drug industry s performance in finishing postmarketing research (Phase IV) studies, a Public Citizen s Health Research Group report, [Internet]. URL http // www.citizen.org/hrg/PUBLICATIONS/1520.htm, accessed 4-14-2000. 

Sasich, L., Lurie, P, and Wolfe, S.M., The drug industry s performance in finishing postmarketing research (phase IV) studies, letter and report from Public Citizen, Health Research Group Publication 1520, Washington, DC, April 13,2000. 

Studies indicate a significant trend toward higher rates of Ml and strokes with increasing doses of progestin in combination oral contraceptives. There have been postmarketing reports of Ml coincident with levonorgestrel implant system use. 

The most common adverse reaction to etanercept is mild to moderate erythema, pain, or pruritus at the injection site (37%). Headaches and abdominal pain can also occur. New positive autoantibodies, such as antinuclear antibodies (ANA), anti-dsDNA antibodies, and anticardiolipin antibodies, can develop in patients treated with etanercept. Although there is so far no association between this and the development of autoimmune diseases or malignancies, long-term studies have yet to be done. Rare cases of pancytopenia may be associated with this drug. Although clinical trials showed no increased risk of infection with etanercept treatment, postmarketing reports of serious infections, sepsis, and associated fatalities exist. 

Adverse effects. Postmarketing surveillance, in which more than 34,000 patients were studied, revealed that fluvoxamine is generally well tolerated if initial dose titration is employed (Wilde et al. 1993). By far the most common side effect reported was nausea (15.7%) other adverse effects included somnolence (6.4%), asthenia (5.1%), headache (4.8%), and dry mouth (4.8%) these events had an incidence of >1%. On reviewing the manufacturer s database, Henry (1991) found that 310 cases of overdose with fluvoxamine had been reported worldwide. The overwhelming majority recovered with no sequelae the 13 fatalities were associated with multiple substance ingestion, making the contribution of any single substance difficult to assess. 

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