TABLE 1.
Comparison of Schemes
| Level | Proposed scheme | Fryback and Thornbury scheme |
|---|---|---|
| 1 | In vitro characterization | Technical efficacy |
| Kon, Koff, Kd, Bmax, and IC50 Partition coefficient and binding potential |
||
| Labeling efficiency and yield | ||
| In vitro label stability | ||
| 2 | In vivo animal studies | Diagnostic accuracy |
| In vivo stability | ||
| Target vs. nontarget tissue specificity | ||
| Pharmacokinetics | ||
| Radiochemistry optimization | ||
| Dosimetry and toxicity | ||
| 3 | Initial human studies | Diagnostic thinking |
| Safety, dosimetry, and target specificity | ||
| Tracer stability in vivo | ||
| Pharmacokinetics (including metabolites) | ||
| Reproducibility | ||
| Determination of sensitivity, specificity, PPV, and NPV IND application | ||
| Chemistry, manufacturing, and controls development | ||
| 4 | Impact on clinical care (change in management) | Therapeutic efficacy |
| Diagnosis (patients with suspicion of disease) | ||
| Staging (patients with known disease) | ||
| Response to therapy (imaging before and after therapy) | ||
| Evaluation for targeted therapy | ||
| Current-good-manufacturing-practices implementation | ||
| 5 | Impact on patient outcome | Patient outcomes |
| Assessment of implementation of change in management | ||
| Assessment of correctness of change in management | ||
| Survival with and without test (Kaplan–Meier plots) | ||
| Quality-adjusted life years | ||
| 6 | Societal efficacy | Societal efficacy |
| Cost-benefit analysis | ||
| Risk-benefit analysis | ||
| Postapproval monitoring for side effects |
Kon = binding rate constant; Koff = release rate constant; Kd = dissociation constant; Bmax = maximum number of binding sites; IC50 = inhibitory concentration of 50%; NPV = negative predictive value; PPV = positive predictive value.