Under-reporting

Estimated worldwide sales excluding Japan. Based on audited sales adjusted for under reporting. Sales of less than 10 million per annum not included. 

The second major change enacted under the 1962 amendment was the change in the approval process from premarket notification to a premarket approval system. Under the terms of the 1938 law, an NDA would take elfect automatically if the FDA did not respond. For example, the only reason thalidomide was not approved was because Dr. Kelsey returned the application to the sponsor with a request for more information. In contrast, the 1962 law required affirmative FDA action before a drug could be put on the market. Under the terms of the 1962 amendments, the FDA was also empowered to withdraw NDA approval and remove the drug from the market for a variety of reasons, including new evidence that the product was unsafe or that the sponsor had misrepresented or under-reported data. 

Events are under-reported in a passive surveillance system because of the failure to recognize an adverse event as being related to a food additive, the amount of effort involved, or other reasons. 

Even in areas in which shellfish poisonings are endemic, cases of these diseases are substantially under-reported. McKee et al. (2001) studied the diagnosis, treatment, and reporting of CFP in Miami-Dade County, Florida. They found that physicians had little experience of recognizing the disease, were unaware of a possible treatment (i.e., intravenously administered mannitol), and were thus unable to provide information to their patients to prevent further cases of the disease. This suggests that, despite the fact that these diseases have been known for more than 150 years, the diseases... 

It is usual for a subject to under-report the intake or to consume less than usual, if intake is being monitored by an observer. 

Ciguatera is also an American problem and is grossly under-reported. My files contain numerous reports of poisonings which occurred while on vacation or from fish obtained in a hot area. 

The majority of foodbome illness associated with enteric viruses are short-lived and not life threatening (Kurdziel et al., 2001). Tracing sources of enteric viruses is problematic due to the lack of routine detection techniques combined with under-reporting of outbreaks (Kurdziel et al., 2001). 

Under-reporting, reports of known reactions, and false causality attribution are the common criticisms of spontaneous reporting systems. Several studies show that workload, doubt about causal relationship, and doubt about whether it is worth reporting, are the common reasons for under-reporting. It follows that the attribution of causality is at least as good as any other careful clinical diagnosis, often after the exclusion of other disease (because doctors are less likely to report where there is doubt over causality) if under-reporting is due to workload, then there must be a real motivation to send a report. 

Adverse effects have been documented for a variety of dietary supplements however, under-reporting of adverse effects is likely since consumers do not routinely report, and do not know how to report, an adverse effect if they suspect that the event was caused by consumption of a supplement. Furthermore, chemical analysis is rarely performed on the products involved, including those products that are described in the literature as being linked to an adverse event. This leads to confusion about whether the primary ingredient or an adulterant caused the adverse effect. In some cases, the chemical constituents of the herb can clearly lead to toxicity. Some of the herbs that should be used cautiously or not at all are listed in Table 64-1. 

Since the relationship between physicians and pharmaceutical companies is open to abuse in a myriad of ways, safeguards are necessary to reduce the chances of a duality of interest becoming a conflict of interest and corruption. Because abuses have occurred in the past and because positive outcomes are usually not reported or are under-reported, there is a tendency for the public to label the relationship as "bad."... 

Most of the information about the long-term safety of somatropin in children has been derived from databases voluntarily maintained by two pharmaceutical companies thus, there may be under-reporting. Other trials have generally been of short duration, with few participants, and may thus have been subject to type II error. The effectiveness and safety of somatropin in children has been the subject of a systematic review (108). 

It should be noted by the reader that this section is based upon clinical research information, personal experiences, and returns from surveys of athlete s whom have used the drugs listed. In the Drug References Descriptions section under Reported Characteristics listings such as Average Reported Dosages are based upon interviews with athlete s and the survey returns from polled athletes and are not in any wav meant as a recommendation or advise. 

Under reported conditions,104 the only tractable product from rearrangement of 241 was alcohol 271, isolated in 79% yield as shown in Scheme 24. From a mechanistic standpoint, it would seem that radical 267 is a probable precursor to 271, while it is less clear how 270 is derived from 241. Homolysis of the peroxide bond of 241 could lead to either 267 or 268. If C-4 H-atom abstraction from 268 were to occur giving radical 269, then it would be more difficult to explain the product 271. In fact, a more reasonable product of radical 268 might be the epoxide 272 which was, however, not formed in this reaction. 

In residents of Seveso, Italy, a significant rise in the incidence of birth defects, as compared to pre-accident levels, was observed the year after the accident (Bisanti et al. 1980). A variety of birth defects were observed, but the incidence for any particular defect was not elevated. The authors suggest that the rise in birth defects may not be related to 2,3,7,8-TCDD exposure. Prior to 1976, birth defects in Italy were usually under reported the authors note that the reported incidences of birth defects after the accident (23 per 1,000 births) were similar to incidences reported in other western countries. Thus, the increased incidence may be reflective of the increased reporting rather than an increased number of birth defects. In a study which assessed the risk of birth defects for the 6-year period after the Seveso accident, no increases were observed for the risk of total defects (RR of 1.2, 90% Cl of 0.88-1.64 for zones A and B and RR of 0.97, 90% 0=0.83-1.13 for zones A, B, and R), major defects RR of 1.02, 90% 0=0.64-1.61 for zones A and B and RR of 0.83, 90% 0=0.67-1.04 for zones A, B and R), and minor defects RR of 1.44 90% 0=0.92-2.24 for zones A and B and RR of 1.14, 90% 0=0.92-1.42 for zones A, B and R) (Mastroiacovo et al. 1988). The small number of observed birth defects limits the statistical power of this study to detect significant increases in a specific defect. 

Adverse affects Commonly observed adverse effects of fluoxetine are summarized in Figure 12.7. Loss of libido, delayed ejaculation and anorgasmia are probably under-reported side effects often noted by clinicians but are not prominently featured in the list of standard side effects. Overdoses of fluoxetine do not cause cardiac arrhythmias but can cause seizures. For example, in a report of patients who took an overdose of fluoxetine (up to 1200 mg compared with 20 mg/day as a therapeutic dose) about half of the patients had no symptoms. 

Acute laryngeal dystonia is probably under-reported but it is potentially lethal and can mimic anaphylaxis (204). It can occur within hours to days of starting therapy with neuroleptic drugs and is characterized by sudden onset of difficulty in breathing and swallowing (SEDA-22, 51). 

Yin Foo Lee G, Wooi Kee Gong G, Vrodos N, Patrick Brophy B. Ecstasy -induced subarachnoid haemorrhage an under-reported neurological complication J Clin Neurosci 2003 10 705-7. 

Erythromycin has been associated with complications such as confusion, paranoia, visual hallucinations, fear, lack of control, and nightmares. These suspected psychiatric adverse effects were seen within 12-48 hours of starting therapy with conventional doses. Such complications may even be under-reported (256-259). 

Another interesting feature of the study was the unreliability of the absolute number of individuals who self-reported cocaine use and the underestimation of cocaine use by urinalysis there is an approximately threefold under-reporting of cocaine use as compared to the positive rate by hair analysis, whereas the positive rate by unannounced urine testing was approximately half that of hair analysis. 

Limitations of FDA spontaneous reporting include both under-reporting and over-reporting. 

A metallic taste due to antimonials is uncommon but probably under-reported (SEDA-16, 311). 

In a report of generalized urticaria after skin cleansing with and urethral instillation of chlorhexidine-containing products, the authors suggest that there is under-reporting... 

The author of a review of the safety of homeopathic products concluded that they are usually safe, but that continued vigilance is in order, not least because of the currently high popularity of homeopathy (138). In response, it was pointed out that under-reporting is high, that homeopathic products are often mistaken for herbal medicines, and that the main risks of homeopathy relate to the prescriber rather than the medicine (139). 

A survey of 323 UK neurologists disclosed 35 previously unreported cases of serious neurological complications of spinal manipulation (187). This means that in this particular series, under-reporting of adverse events had been 100%. 

Of 230 people who had been exposed to formaldehyde and had asthma-like respiratory symptoms with a bronchial provocation test, 12 were considered to be caused by specific sensitization to formaldehyde, 11 were triggered by a concentration of 2.5 mg/m, and one by 1.2 mg/m (SEDA-11, 477) (8). The authors concluded that formaldehyde-induced asthma, although apparently rare, is under-reported. 

In a retrospective review of 37 patients with chronic non-malignant pain (mostly from failed lumbosacral spine surgery) treated with intrathecal hydromorphone there was an analgesic response in six of the 16 patients who were switched from morphine to hydromorphone because of poor pain relief (1). Opioid-related adverse effects, such as nausea, vomiting, pruritus, and sedation, were also reduced by hydromorphone in the 21 patients who were switched to hydromorphone because of morphine-related adverse effects, especially 1 month after use. These results should be treated cautiously, because of the limitations of a retrospective study that lacks strict inclusion criteria, with obvious population bias and under-reporting, and without standardized procedures for rotation to hydromorphone. 

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