The POWER-tool: Recommendations for involving patient representatives in choosing relevant outcome measures during rare disease clinical trial design

In clinical trials, it is relevant to ask patients and/or their caregivers which aspects concerning their disease they consider important to measure when a new intervention is being investigated. Those aspects, useful as outcome measures in a trial, are of pivotal importance for the result of the trial and the subsequent decision-making. In rare diseases the choice of outcome measures may be even more important, due to the small numbers and heterogeneity of the patients that are included.We have developed a tool to involve patients in the determination of outcome measures and the choice of measurement instruments. This tool was developed together with a patient think tank, consisting of a group of rare disease patient representatives, and by interviewing end users. We have road-tested our tool in an ongoing trial, and evaluated it during a focus group meeting.The tool consists of three steps: 1) Preparation, 2) Consultation of patients, 3) Follow-up during which the consultation results are implemented in the trial design.The tool provides guidelines for researchers to include the patient’s opinion in the choice of outcome measures in the trial design stage. We describe the development of the POWER-tool (Patient participation in Outcome measure WEighing for Rare diseases), and first experiences of the tool in an ongoing trial.     

High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in Luminal B HER2 negative and node-positive breast cancer

BackgroundThe indication of adjuvant chemotherapy for patients with highly proliferative estrogen receptor-positive breast cancer is controversial. We analyzed the predictive value of Ki67 for the efficacy of adjuvant chemotherapy in patients with estrogen receptor-positive, node-positive breast cancer.Patients and methodsWe identified 1241 patients with Luminal B early stage breast cancer with 1–3 axillary positive nodes who underwent surgery between 1995 and 2005 at the European Institute of Oncology and received adjuvant hormonotherapy and/or chemotherapy. Differences in the distribution of characteristics according to treatment were evaluated by the Chi-square test. To evaluate the effect of adding chemotherapy to hormonotherapy, the propensity score method was used to match patients' characteristics minimizing bias related to the non-random assignment of treatment.ResultsThe probability of receiving chemotherapy was significantly associated with age, tumor grade, degree of hormone responsiveness, tumor size and peripheral vascular invasion. The propensity score distribution was statistically different between the two treatment groups (p < 0.0001). The 5-year OS percentages were 95.8% (95% CI, 93.5–97.2) in the hormonotherapy group and 96.2% (95%CI, 94.4–97.4%) in the hormonotherapy/chemotherapy group (log-rank test p-value 0.663). The 5-year DFS percentages were 84.6% (95% CI, 81.0–87.6%) in the hormonotherapy group and 84.2% (95% CI, 81.3–86.7%) in the hormonotherapy/chemotherapy group (log-rank test p-value 0.388). However, when analyzing the 5-year DFS by Ki-67 distribution, Subpopulation Treatment Effect Pattern Plot (STEPP) analysis showed a beneficial effect of chemotherapy in patients with highly proliferative tumor (Ki-67 ≥ 32%). The interaction between Ki-67 and treatment was statistically significant (p = 0.027).ConclusionsKi67 expression identifies a subset of patients with Luminal B and node-positive breast cancer who could benefit from addition of adjuvant chemotherapy to hormonotherapy. Dichotomy was observed for Ki67 at 32% level.     

Time in Parenting Activities in Dual‐Earner Families at the Transition to Parenthood

Time parenting was compared for new mothers and fathers in a sample of 182 dual‐earner families. Parenting domains included positive engagement, responsibility, routine child care, and accessibility. Time diaries captured parents' time use over a 24‐hour workday and nonworkday when infants were age 3 and 9 months. Parents were highly involved with their infants. Mothers were more involved than fathers in positive engagement and routine child care on days and at each assessment, and allocated more available time on workdays to these domains than fathers, with one exception. Fathers and mothers allocated similar shares of available workday time to positive engagement at 9 months. Greater equity in responsibility and accessibility was found; mothers spent more, and a greater share of, parenting time in responsibility than fathers on the 9‐month workday only, and were more accessible on the 3‐month workday only. Implications for parents in today's diverse families are discussed.