Clinical hazard

It is not common practice to screen routinely for this disorder as the milder variants are not clinically hazardous, and screening for the rarer variants is impractical. In high-prevalence populations (Africans, Mediterranean) however, there should be a high index of suspicion in patients presenting with appropriate clinical symptoms. 

Acute salicylate poisoning is a major clinical hazard (96), although it is associated with low major morbidity and mortality, in contrast to chronic intoxication (SEDA-17,... 

Finding a new indication is an obvious opportunity to increase market size by enlarging the potential pool of patients that can benefit from the product. In this case, two pivotal, well-controlled phase IV studies demonstrating efficacy will usually be required, at a minimum. If there is the potential for a new type of clinical hazard to be associated with new disease being studied, then a safety database, of a size that regulators will find acceptable, will be needed for the supplemental application, too. Clearly, whenever such a project is contemplated, then a financial assessment is needed of the balance between the cost of the program, the probability of success and the size of the eventual revenue increment that may or may not justify it. 

A drug interaction is an effect observed with two or more drugs, which is not seen with one drug alone. The effect can be qualitative or quantitative. Drug interactions can constitute clinical hazard or be exploited for therapeutic benefit. 

It is a curious assumption, and illogical that a complementary therapy could have sufficient pharmacological activity to improve health (however imprecisely that may be defined), and yet these properties are automatically insufficient to cause harm. Part of the problem is that adverse reactions to natural therapies are not reported in the same way as for orthodox drugs (Barnes et al., 1998). Reporting bias also tends toward the association of adverse effects with the condition being treated rather than from the harmless over-the-counter or herbal remedy that has been administered. The only complementary therapies that are safe in overdose are those that are homeopathic, with even these carrying the clinical hazard of under-treatment. 

Note, however, that amendments that are made to reduce an immediate clinical hazard to the trial participants may be implemented immediately, and remains the primary responsibility of the designated medical monitor for the study, without prior written approval from the ethics committee. However, the investigator is under obligation to inform the ethics committee, the sponsor must inform the RA, both as soon as possible and in any case within 72 h (see European Commission Directive 2003/94/EC, 2005/28/EC). 

Before the trial is started, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. [However, the Declaration has a central tenet that civilians must not be subjected to undue clinical hazards, without any potential for benefit themselves, but in order to benefit society at large.]... 

Clinical hazard has two aspects. The most obvious aspect is avoiding the inappropriate exposure of a patient to a potentially harmful drug. But let us not forget that clinical hazard can also be created by restrictions on product distribution channels if these are too rigourous, then the drug... 

These common situations are discussed in the previous chapters on regulatory affairs. They can be viewed as the default set of risk management programs to be implemented in the absence of any special clinical hazard. 

What sorts of drugs and indications have special clinical hazards and need special risk management programs At the pan-European level, the EMEA now considers risk management plans more or less routinely prior to Marketing Authorization. But in general, the products for which detailed risk management plans will almost always be required are... 

Major clinical hazard, mifepristone. This prostaglandin analog is capable of inducing abortion of a uterine pregnancy of less than 49 days duration when administered orally. In 2000, it was approved in the United States amidst controversy associated with the cultural aspects of pregnancy and its termination. 

At the time of writing, about four years have elapsed since product launch. The most widely reported serious adverse events during those four years have been four cases of fatal sepsis, a clinical hazard that is much smaller than the general risks associated with pregnancy to full term. 

This is an example of a risk management program that currently appears to have been scaled appropriately for the minimization of direct clinical hazard. Cultural aspects of this form of therapy continue to provoke protest at product availability, and reported adverse events are also used to keep these protests in the public eye. 

The USP specifies that injectable products be 100% inspected to ensure that the product is free from visible foreign particulate matter (< 788>). This is crucial because particulate matter in injectable drug products is considered a clinical hazard. Particulate matter has been implicated in the formation of granulomas in various internal organs in rats, as well as embolisms and phlebitis in humans.4 Pulmonary capillaries (the smallest capillary vessels in the human body) are about 7 (tm in size. This is why determination of particles about 7 Lm and larger is deemed important. 

Information is very limited, but on the basis of the evidence cited above the manufacturers of astemizole contraindicate the concurrent use of quinine in order to avoid the risk of cardiac arrhythmias. The case report that is cited here confirms that this is a potentially clinically hazardous drug combination. ... 

Kenneback G, Bergfeldt L, ValUn H, Tomson T, Edhag O. Electrophysiologic effects and clinical hazards of carbamaze-pine treatment for neurologic disorders in patients with abnormahties of the cardiac conduction system. Am Heart J 1991 121 (5) 1421-9. 

All these observations and findings will be included in the Clinical Investigators Brochure (CIB). Indeed, the initial guidance for clinical hazard potential may depend almost entirely on safety pharmacology findings because of an unspectacular toxicology profile, the lack of human exposure, and the fact that normal volunteers are unlikely to be capable of exhibiting certain adverse event types... 

Where the health organisation identifies clinical hazards with these interoperations, it follows that the hazardous aspects of the interface be subject to more rigor and additional controls/validation than would be the case currently. In some health organisations there is no existing capacity to perform this kind of application validation and testing. 

---