Clinical drug safety issues

Such support can involve responding to complaints about promotional activities, which may come from other companies or external agencies such as, in the UK, the Prescription Medicines Code of Practice Authority. A medically qualified person should certainly have overall responsibility for clinical drug safety issues (see Section 9.3.6). Pharmaceutical physicians are usually involved in the training of sales representatives. In addition, a good pharmaceutical physician can be a credible ambassador for the company when lecturing to external audiences or dealing with the communication media. 

Other activities that fall within the area of postmarketing surveillance require input from, if not handling by, those responsible for clinical drug safety. These may include observational (non-interventional) studies, which may be retrospective or prospective, and other projects specifically designed to investigate a safety issue. 

The science of pharmacovigilance - monitoring and evaluating drug safety issues and communicating them effectively - is a vital activity of worldwide significance in the safeguarding of patient welfare and public health. Its clinical, public health and economic importance has been demonstrated, but it needs to be better understood and appreciated by politicians, the media and the public. 

Healthcare professional sheet Concise summary of an important, and often emerging, drug safety issue, with background information about the detection of the issue and points to consider for clinical decision making Healthcare professionals... 

Thus, it can be seen that every section of the clinical advice in the SPC might potentially need to be modified in relation to a new drug safety issue. 

The first issue lies in the whole realm of the human disease process itself. Many adverse drug events mimic diseases and vice versa. Is an adverse event really an adverse event, or is it merely a natural occurrence of a disease process that is entirely independent of drug exposure The science of drug safety is often complicated by the lack of objective markers of drug toxicity that can systematically separate a disease process from an adverse drug event process [2]. Clinical trials, often viewed as the gold standard to assess efficacy, are simply too limited in scope to answer safety questions in a systematic way. 

Fig. 21.2. Reasons why the clinical development of drugs is sometimes terminated and the drug does not reach the market include safety issues, marketing reasons, lack of efficacy and/or pharmacokinetics/bioavail-...

A final challenge for early screening is the detection of genotoxic impurities and synthetic intermediates which can create occupational/manufacturing as well as patient safety issues. This again is a complex issue because the material screened from a library might be synthesized and purified by different routes to a drug that enters the clinic. These issues are addressed in a later section. 

The main information on safety of drugs in regular use is obtained from doctors reports of clinical concerns (ICSR) and published case reports from health professionals, post-marketing clinical studies, controlled retrospective or prospective studies, and case series. The studies may or may not have safety issues as their major focus. 

Before a drug may be tested on humans, it must first be tested on animals. Tests on humans are called clinical trials, and animal trials are often referred to as preclinical trials. Preclinical trials differ from the animal tests mentioned earlier in this chapter. The previously discussed animal tests help the drug discovery team determine and optimize the pharmacodynamic and pharmacokinetic behavior of a hit or lead. Preclinical trials, in contrast, are standardized, industrywide tests. The preclinical tests have technical names such as Segment II Reproductive Study in Rabbits or 6-Month Toxicity Study in Rats. The specific names suggest the exact nature of each study. Each trial seeks to answer predefined safety questions concerning a drug candidate. Preclinical trials do not address the therapeutic effectiveness of the drug candidate in any way. Preclinical trials examine exclusively safety issues. 

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