Risk/benefit balance

Although medical products are required to be safe, safety does not mean zero risk. A safe product is one that has reasonable risks, given the magnitude of the benefit expected and the alternatives available. All participants in the medical product development and delivery system have a role to play in maintaining this benefit-risk balance by making sure that products are developed, tested, manufactured, labeled, prescribed, dispensed, and used in a way that maximizes benefit and minimizes risk. ... 

It will be seen that the factors of seriousness, duration and frequency are common to both sides of the benefit-risk balance. This is a help in making a decision about a drug, but there is a problem with adverse reactions, since many are possible with differing seriousness etc. They must be summarised, perhaps best by considering the most serious and most common, and then comparing with the benefit of the drug (see Edwards et ah, 1996). 

Stop those dmgs likely to be causing serious reactions and whose benefit/risk balance in this situation is not good. 

Gordon AJ, editor. Benefit-risk balance for marketed drugs evaluating safety signals. Report of CIOMS Working Group IV. Geneva WHO Press 1998. 

Govoni S, Trabucchi M, Cagiano R, Cuomo V. 1994. Alcohol and the brain setting the benefit/risk balance. Alcohol 11 241-246. 

No drug is 100% safe in 100% of patients. Comparative evaluation, or benefit-risk balancing of pharmaceutical products is inevitable. Furthermore, there are no absolute or arithmetical standards for this it is part of the art of practicing medicine, if at a large than usual scale of conducting what is essentially an n = 1 clinical trial every time a prescription is written. Thus, the definitions and terms chosen depend entirely on the context in which they are used, and on the user, in a case-by-case manner. These complexities are not always obvious to information users, such as patients and their lawyers. But again, the factors influencing benefit-risk assessments include... 

CIOMS Working Group IV. 1999. Benefit-Risk Balance for Marketed Drugs. Evaluating Safety Signals. CIOMS Geneva. 

Only when there is an acceptable benefit-risk balance in terms of public health and risk to the individual patient should bioequivalence testing according to the guidelines given in this section be permitted. 

Mibefradil is the first calcium antagonist known to selectively block T-type calcium channels. It is highly effective against hypertension and angina pectoris, and significantly improves the benefit-risk balance in comparison with drugs which have similar targets. 

The chapter is organized along the risk management process and will discuss the topics of risk identification, risk characterization, benefit-risk balance, and risk minimization. Dependence on other regulatory documents with relevance to safety will be pointed out throughout all sections. 

Coplan PM, Noel RA, Levitan BS, Ferguson J, Mussen F. Development of a framework for enhancing the transparency, reproducibility and communication of the benefit-risk balance of medicines. Clinical Pharmacology and Therapeutics 2010 89(2) 312-315. 

Interest in subgroup analysis has intensified in recent years due to the development of targeted therapies under the broad theme of personalized medicine. While most of the attention on targeted therapies is currently focused on efficacy, safety will play an important role as the ultimate decision on a therapy is the balance between benefit and risk. While increasing benefit is one way to increase the benefit/risk balance, reducing adverse reaction could also lead to a more favorable benefit/risk profile for a subgroup of patients. 

If the medicine is used for other indications its benefit risk balance will be different and should be assessed again. If not the medicine is used off-label . 

The ICH QIO guideline is developed as a PQS model for the whole life cycle of an industrially made product. It therefore starts with the design phase of the product and ends with product discontinuation. It does not include however the very first step the therapeutic issues (prescription assessment, benefit/risk balance) which are relevant for pharmacy preparations. 

A similar decision process occurs at the level of the individual patient once a relevant drug is approved the physician and the patient must decide together that a particular course of pharmacotherapy has a favorable benefit-risk balance for the drug to be prescribed. 

---