Cost-Effectiveness of Surveillance Programs of Carriers of Pathogenic Mutations in the TP53-Gene in Sweden

Abstract: Introduction: Pathogenic mutations in the TP53-gene is present in about 50% of all somatic cancers. The TP53 gene’s function is to stop cancer cells from dividing, thus protect us from cancer. When this gene is not functioning properly, carriers face 70-100% risk of developing cancer in their lifetime. Early diagnosis of cancer improves survival and currently individuals with pathogenic hereditary mutations in this gene are entitled to an extensive surveillance program to increase early detection of cancer. A new study, the Swedish TP53 study (SWEP53), is investigating a surveillance program offering whole-body magnetic resonance imaging (WBMRI) of confirmed carriers. It is not known if the potential health effects of such surveillance programs justify the additional costs. The objective of this thesis was to determine whether any of the surveillance programs are cost-effective in Sweden. Methods: A novel decision analytic model was developed using a health care perspective covering the lifetime of carriers of mutations in TP53. Nine different cancers were modelled. All cancers carry a cost. an impact on health-related quality of life and survival. Three separate scenarios were investigated; no surveillance, surveillance by current standard of care and surveillance using WBMRI as proposed in the SWEP53-study. The total costs and total quality adjusted life years (QALY) of each scenario were used to calculate incremental cost-effectiveness ratios for the current standard of care and the SWEP53-protocol. Results: Surveillance of both male and female carriers of pathogenic mutations in TP53 carries an incremental cost-effectiveness ratio of 748 194 SEK. Surveillance using is WBMRI carries a cost of more than seven million SEK. If the annual probability of diagnosis is ca 40-50 percentage points higher than in the standard of care this may change to a level similar to SOC in the current analysis. The greatest uncertainty of the results lay in the estimation of the impact on survival from cancer diagnosis and annual probability of diagnosis. Conclusion: The incremental cost per QALY of the current surveillance program is likely acceptable in Sweden given the rarity and severity of being a carrier of a hereditary pathogenic mutation in TP53. Surveillance using WBMRI carries an incremental cost per QALY that is much higher than what is traditionally acceptable in Sweden. The clinical benefit of surveillance using WBMRI in relation to current surveillance is unclear and more data is needed. This analysis is made under great uncertainty but shows that when analyzing hereditary mutations, it is imperative to consider the whole spectrum of attributed disease as this greatly impacts the cost-effectiveness of e.g. surveillance. These estimates may be uncertain but as of today this is the only and the best estimate available.