Generating and evaluating evidence of the clinical utility of molecular diagnostic tests in oncology.

PURPOSE: Enthusiasm for molecular diagnostic (MDx) testing in oncology is constrained by the gaps in required evidence regarding its impact on patient outcomes (clinical utility (CU)). This effectiveness guidance document proposes recommendations for the design and evaluation of studies intended to reflect the evidence expectations of payers, while also reflecting information needs of patients and clinicians. METHODS: Our process included literature reviews and key informant interviews followed by iterative virtual and in-person consultation with an expert technical working group and an advisory group comprising life-sciences industry experts, public and private payers, patients, clinicians, regulators, researchers, and other stakeholders. RESULTS: Treatment decisions in oncology represent high-risk clinical decision making, and therefore the recommendations give preference to randomized controlled trials (RCTs) for demonstrating CU. The guidance also describes circumstances under which alternatives to RCTs could be considered, specifying conditions under which test developers could use prospective-retrospective studies with banked biospecimens, single-arm studies, prospective observational studies, or decision-analytic modeling techniques that make a reasonable case for CU. CONCLUSION: Using a process driven by multiple stakeholders, we developed a common framework for designing and evaluating studies of the clinical validity and CU of MDx tests, achieving a balance between internal validity of the studies and the relevance, feasibility, and timeliness of generating the desired evidence.Genet Med 18 8, 780-787.

Stakeholder-driven principles for advancing equity through shared measurement.

OBJECTIVE: To advance equity by developing stakeholder-driven principles of shared measurement, which is using a common set of measurable goals that reflect shared priorities across communities and systems, such as health care, public health, and human and social services. DATA SOURCES: From October 2019 to July 2021, we collected primary data from leaders in cross-systems alignment, measurement, and community engagement-including community members and community-based organization leaders-across the United States. STUDY DESIGN: In partnership with equity and community engagement experts, we conducted a mixed-methods study that included multiple formative research activities and culminated in a six-week, stakeholder-engaged modified-Delphi process. DATA COLLECTION: Formative data collection occurred through an environmental scan, interviews, focus groups, and an online survey. Principles were developed using a virtual modified Delphi with iterative rapid-analysis. Feedback on the final principles was collected through virtual focus groups, an online feedback form, and during virtual presentations. PRINCIPAL FINDINGS: We developed a set of five guiding principles. Measurement that aligns systems with communities toward equitable outcomes: (1) Requires upfront investment in communities; (2) Is co-created by communities; (3) Creates accountability to communities for addressing root causes of inequities and repairing harm; (4) Focuses on a holistic and comprehensive view of communities that highlights assets and historical context; and (5) Reflects long-term efforts to build trust. Using an equity-focused process resulted in principles with broad applicability. CONCLUSIONS: Leaders across systems and communities can use these shared measurement principles to reimagine and transform how systems create equitable health by centering the needs and priorities of the communities they serve, particularly communities that historically have been harmed the most by inequities. Intentionally centering equity across all project activities was essential to producing principles that could guide others in advancing equity.

Lessons Learned from Developing Plain Language Summaries of Research Studies.

BACKGROUND: Plain language translation may facilitate the public's ability to understand and use results of scientific research. Brief description of activity: This article describes the Patient-Centered Outcomes Research Institute's (PCORI) approach to and lessons learned from developing plain language summaries of PCORI-funded research for the lay public. IMPLEMENTATION: We developed and tested a standard template for the summaries, incorporating feedback in the template design from focus groups with members of the public. Between February 2017 and March 2020, we completed translation of 272 plain language summaries of PCORI-funded studies, covering topics including cardiovascular disease, obesity, cancer, mental health, asthma, HIV/AIDS, and comparative effectiveness research methods. RESULTS: Templates use a question-and-answer format, with sections on the rationale, methods, results, limitations, and how the research will help inform decisions. In addition to feedback on template heading wording and order, focus group participants stressed the importance of establishing relevance and conveying credibility and limitations. LESSONS LEARNED: Lessons learned relate to supporting consistency across individual summaries, carefully prioritizing content to include in the summaries, and balancing plain language and reading level with precision. These lessons learned from template development and implementation may be useful to other organizations or publishers contemplating similar efforts to make scientific research results more accessible. [HLRP: Health Literacy Research and Practice. 2021;5(2):e155-e161.] Plain Language Summary: The Patient-Centered Outcomes Research Institute (PCORI) funds comparative effectiveness research. This research compares the benefits and harms of two or more health care choices. In this article, we describe lessons learned from PCORI's efforts to develop plain language summaries of results from the research it funds. These lessons may help other organizations that want to share research results in plain language.

Neoadjuvant chemotherapy for epithelial ovarian cancer--role of apoptosis.

BACKGROUND: Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage. Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression. Little is known about the effect of various treatment regimens on the distribution of molecular markers of apoptosis in epithelial ovarian cancer. The objective of this study was to compare the expression levels of both proapoptotic and antiapoptotic proteins p53, p73, Bcl-2, Bcl-XL and survivin in the ascitic cells and tumor samples of patients undergoing treatment with two different regimens. METHODS: A total of 24 patients with untreated epithelial ovarian cancer were randomized into two groups of 12 each. Group 1 patients received three cycles of chemotherapy prior to surgery and three cycles after surgery and group 2 patients received six cycles of chemotherapy prior to surgery. The expression of apoptosis-related proteins was analyzed in ascitic fluid and tumor samples by Western blotting and immunohistochemistry. The apoptotic index was also determined in these samples by the TUNEL assay. RESULTS: Significant decreases in antiapoptotic bcl-2 and survivin were seen, accompanied by increases in apoptotic index in tumors that had undergone chemotherapy as compared to the baseline ascites samples. No significant change in bcl-XL was observed. A significant decrease in proapoptotic p53 was also seen. No expression of p73 was observed in tumors or ascites. The findings were similar in groups 1 and 2 patients and were not statistically significantly different, perhaps due to the small sample size (n=12) of each group. CONCLUSIONS: The above findings indicate that chemotherapy in ovarian carcinoma leads to an increase in apoptosis by a p53-independent pathway, which involves the downregulation of antiapoptotic Bcl-2 and survivin but not Bcl-XL. Furthermore, administering neoadjuvant chemotherapy (six cycles) as an alternative form of therapy for advanced epithelial ovarian cancer is more effective in inducing apoptosis than three cycles. However, the findings of this study need to be corroborated using a larger sample.