![two stage sequential testing two stage sequential testing](https://image1.slideserve.com/2714444/slide10-l.jpg)
The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer. Go to the Clinical Considerations section for information on implementation of the C recommendation. Women with a parent, sibling, or child with breast cancer are at higher risk for breast cancer and thus may benefit more than average-risk women from beginning screening in their 40s. Beginning mammography screening at a younger age and screening more frequently may increase the risk for overdiagnosis and subsequent overtreatment. In addition to false-positive results and unnecessary biopsies, all women undergoing regular screening mammography are at risk for the diagnosis and treatment of noninvasive and invasive breast cancer that would otherwise not have become a threat to their health, or even apparent, during their lifetime (known as "overdiagnosis"). The balance of benefits and harms is likely to improve as women move from their early to late 40s. While screening mammography in women aged 40 to 49 years may reduce the risk for breast cancer death, the number of deaths averted is smaller than that in older women and the number of false-positive results and unnecessary biopsies is larger. Of all of the age groups, women aged 60 to 69 years are most likely to avoid breast cancer death through mammography screening.
![two stage sequential testing two stage sequential testing](https://issues.jenkins.io/secure/attachment/46604/Screenshot%202019-04-02%20at%2009.31.50.png)
For women who are at average risk for breast cancer, most of the benefit of mammography results from biennial screening during ages 50 to 74 years. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. The decision to start screening mammography in women prior to age 50 years should be an individual one. An example is provided to illustrate the procedures.The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. We also compare the proposed procedures with other commonly used group sequential procedures in terms of control of the FWER and the power of rejecting the secondary hypothesis. The procedures control the familywise error rate (FWER) strongly by construction and this is confirmed via simulation. The proposed procedures use the correlation between the interim and final statistics for the secondary endpoint while applying graphical approaches to transfer the significance level from the primary endpoint to the secondary endpoint.
![two stage sequential testing two stage sequential testing](https://support.sas.com/documentation/cdl/en/statug/63033/HTML/default/images/seqt00n.png)
We propose two group sequential testing procedures with improved secondary power: the improved Bonferroni procedure and the improved Pocock procedure. In comparison with marginal testing, there is an overall power loss for the test of the secondary endpoint since a claim of a positive result depends on the significance of the primary endpoint in the hierarchical testing sequence. To control the type I error rate for the secondary endpoint, this is tested using a Bonferroni procedure or any α-level group sequential method. Following a hierarchical testing sequence, the secondary endpoint is tested only if the primary endpoint achieves statistical significance either at an interim analysis or at the final analysis. In two-stage group sequential trials with a primary and a secondary endpoint, the overall type I error rate for the primary endpoint is often controlled by an α-level boundary, such as an O'Brien-Fleming or Pocock boundary.