Genetics

Developing an Evaluation Framework

To accurately evaluate the impact of molecular genetics on common diseases, appropriate criteria to assess the contribution to treatment and prevention must first be available. Key elements of such an evaluation framework must provide answers to questions such as the following: How do the answers provided by this new research fit with what researchers already know? Can molecular tests provide new information about prediction or risk stratification? Will it help to tailor therapy? And will it yield insights into pathogenesis and/or pathways? Answers to these and related evaluation questions will have to be provided by data from the different but dependent stages of molecular genetic research, from discovery to application, as illustrated in Figure 1.

Figure 1 Schematic of Stages in Molecular Genetic Research

A pertinent question therefore becomes, What will the payoff be from finding disease susceptibility variants or loci? The first most likely outcome is improved prediction and/or risk stratification. Experience so far suggests that prediction is an unlikely use of the knowledge of susceptibility loci. To be useful for diagnosis or risk stratification, such a genetic test must substantially increase the posttest probability and also provide supplemental and independent information beyond currently available tests. Based on the assumption that individuals known to be at high risk of developing a disease will benefit from earlier, more intensive intervention, either through lifestyle changes or drugs, risk stratification could also be an important use of the knowledge of disease susceptibility loci. However, in a situation where both exposure and susceptibility are widespread, population-wide measures are often the most effective public health strategy (e.g., smoking, high cholesterol). Likewise, measurement of the phenotype (e.g., high blood pressure) is likely to provide more information than the genotype.

...