Principle of Threes

1. Description

Principle of threes assesses benefit-risk balance using three criteria (disease, effectiveness, and adverse drug reactions) on three attributes (seriousness, duration, and incidence), each scored on three levels 1-3.[1][2][3] Decision maker compares the total scores in disease, effectiveness and ADRs criteria to make the decision. This approach has been modified by introducing the scoring system for benefit and risk separately: (1) ; and (2) .

2. Evaluation

2.1 Principle

• It is a simple multi-criteria model with specific number and level of criteria.

• There is no restriction on the number of options.

• The scoring method is crude or ad-hoc, and it does not consider the relative importance of different criteria.

• It does not account for statistical uncertainties in the data.

2.2 Features

• It allows multiple risk criteria with some modifications, but the risks criteria are weighted equally.

• Risk and benefit are handled separately.

• There is no direct way to handle new data or to accommodate multiple sources of data.

• The appealing feature of this approach is its simplicity; but the simplicity also prevents its application in more complex situations.

2.3 Visualisation

• A simple table is sufficient to visualise the Principle of Threes.

2.4 Assessability and accessibility

• It is easy to perform and understand.

• The scores are to be based on the best current evidence.

• It does not take into account of stakeholder's value preferences.

• It may be useful for quick initial assessments, but not for full benefit-risk assessments.

3. References

[1] Edwards R, Wiholm BE, Martinez C. Concepts in risk-benefit assessment. A simple merit analysis of a medicine? Drug Saf 1996 Jul;15(1):1-7.
[2] CIOMS Working Group IV. Benefit-Risk Balance for Marketed Drugs. Evaluating Safety Signals. 1998. Geneva, Council for International Organizations of Medical Sciences.
[3] Mussen F, Salek S, Walker S. Benefit-Risk Appraisal of Medicines. John Wiley & Sons, Ltd.; 2009.