Risk analysis is a systematic methodology used in an attempt to assess the hazardous or potential harm of an investigational product (Whitmore, 2004). Risk is a relative term in the context of the benefit provided by the product in question.  All medicinal products have risks, therefore, risk is subject to whether a product benefits sufficiently outweighs the risk of the product in question. For this reasons, before the approval of any medicinal product by regulatory agencies, it is required that risk-benefit assessment of the product must be evaluated to assess potential causes of product defects, adverse events (side effects) and the possible consequences of user’s error to mentioned but a few. Avoidance of product defects requires proper maintenance of GMPs and GLPs. An in-depth understanding of the pharmacodynamics (PD), pharmacokinetics (PK), and toxicology evaluation of an investigational product is crucial in ascertaining the safety and efficacy of an investigational product which could be used to mitigate and assess potential adverse events and consequences of user’s error (Ng, 2009). In addition, clinical trial is an important tool that is used to assess the statistical significance of an investigational product, but most importantly, it is also used to assess any clinical significance of the product in question. Furthermore, it is crucial in an intervention and other therapeutic studies to understand whether a product significantly improves a patient’s health well-being over a placebo or comparator (Whitmore, 2004).

The evaluation of risk-benefit assessment may be riskier or complicated by globalization if the study parameters such as intended user population, intrinsic and extrinsic factors are not well-defined. Researchers must know and anticipate the range of the intended end users for any product and conduct the clinical trial to represent the intended users. The issue of intrinsic factors such as pharmacogenetics or polymorphism has significant effects with race or ethnicity in the metabolism, clinical effectiveness and side effects profile of many medicinal products (Whitmore, 2004). Moreover, extrinsic factor such as epidemiological and environmental predisposition such as previous exposure to treatments may have effects on study subjects. Hence, it is very important while globalizing clinical trials to understand these limiting factors, account for the unknown and apply a sound scientific rationale.

A scenario to think about and use as a reference to pharmacogenetic issues is the P450 2D6 mutation that occurs among 7% of Caucasian population. Someone that has this mutation cannot metabolism molecules facilitated by Cytochrome P450 2D6 (Ng. 2004). This particular situation may lead to serious adverse events on subjects (Mutants) using medicinal product, which are composites of molecules metabolized or facilitated by cytochrome P450 2D6. It may also lead to improper labeling of a product if these subjects population is not represented in the clinical trial before the approval of the product. User error in this situation will apply if these sets of CYP450 2D6 mutants population uses the medication when they are not supposed it or are using it in the wrong dosage that will not compensate for the metabolic deficiency.

References

NG. R. (2009). Drugs: From discovery to approval (2nd ed.). Hoboken, NJ: Wiley-Blackwell.

Whitmore, E. (2004). Development of FDA-regulated medical products: Prescription drugs, biologics, and medical devices. Milwaukee, WI: ASQ Quality Press.