Developing the Process and Tracking the Implementation and Evaluation of the National Institutes of Health Strategic Plan for Women's Health Research.

The National Institutes of Health (NIH) released Advancing Science for the Health of Women: The Trans-NIH Strategic Plan for Women's Health Research, 2019-2023 (Strategic Plan) in February 2019. The NIH Office of Research on Women's Health (ORWH) engaged staff members from across NIH to develop recommendations on the implementation and evaluation of the Strategic Plan. OBJECTIVE: This paper describes the process used to develop recommendations for tools and approaches that NIH Institutes, Centers, and Offices (ICOs) could apply when implementing and evaluating the Strategic Plan. METHODS: A Trans-NIH Strategic Plan Implementation and Evaluation Guidance Development Team conducted meetings and individual interviews with 69 NIH staff members knowledgeable about research on the health of women and sex and gender differences and met with 11 Advisory Committee on Research on Women's Health Strategic Plan Evaluation Working Group members. The purpose of these stakeholder meetings and interviews was to obtain recommendations for implementing the Strategic Plan and identify measures for evaluating implementation success. A thematic analysis was performed to synthesize and map the recommendations to the Strategic Plan goals and objectives. RESULTS: The process resulted in the Guide for Implementing and Evaluating the 2019-2023 Trans-NIH Strategic Plan for Women's Health Research Across NIH Institutes, Centers, and Offices (the Guide), which includes both a conceptual and logic model for implementation and evaluation. CONCLUSIONS: The Guide offers methods, tools, and suggestions that ICO planning and evaluation staff, as well as national and international entities, can choose from when determining how to implement the Strategic Plan through ICO activities, programs, and research initiatives and how to evaluate their efforts in the context of their unique mission.

Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies.

Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). However, appropriate clinical outcome measures to be used in clinical trials have not been validated in CMDs. We conducted a two-year pilot study to evaluate feasibility, reliability, and validity of various outcome measures, particularly the Motor Function Measure 32, in 33 subjects with COL6-RD and LAMA2-RD. In the first year, outcome measures tested included: Motor Function Measure 32 (MFM32), forced vital capacity (FVC) percent predicted sitting, myometry, goniometry, 10-meter walk, Egen Klassification 2, and PedsQL(TM) Generic and Neuromuscular Cores. In the second year, we added the North Star Ambulatory Assessment (NSAA), Hammersmith Functional Motor Scale (HFMS), timed functional tests, Measure of Activity Limitations (ACTIVLIM), Quality of Upper Extremity Skills Test (QUEST), and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue subscale. The MFM32 showed strong inter-rater (0.92) and internal consistency (0.96) reliabilities. Concurrent validity for the MFM32 was supported by large correlations (range 0.623-0.936) with the following: FVC, NSAA, HFMS, timed functional tests, ACTIVLIM, and QUEST. Significant correlations of the MFM32 were also found with select myometry measurements, mainly of the proximal extremities and domains of the PedsQL(TM) scales focusing on physical health and neuromuscular disease. Goniometry measurements were less reliable. The Motor Function Measure is reliable and valid in the two specific subtypes of CMD evaluated, COL6-RD and LAMA2-RD. The NSAA is useful as a complementary outcome measure in ambulatory individuals. Preliminary concurrent validity of several other clinical outcome measures was also demonstrated for these subtypes.

Predictors of functional shoulder recovery at 1 and 12 months after breast cancer surgery.

The objective of this study are (1) to determine if upper extremity function, as represented by shoulder ROM, self-reported symptoms and upper extremity functional limitations in activities of daily living could be predictively related to demographic and cancer characteristics post-surgery for breast cancer. And (2) to examine if variables related to early onset impairment contribute to late onset impairments in women after breast cancer surgery. Subjects were assessed preoperatively and 1, 3, 6, 9, and 12+ months post breast cancer surgery for impairments and symptoms and at 12+ months for shoulder functional limitations using a physical therapy surveillance model. Body weight, shoulder ROM, manual muscle testing, and upper limb volume were recorded. At 12+ months, the Harvard Alumni Health Study Physical Activity Questionnaire, and an Upper Limb Disability Questionnaire were administered. Symptoms and ROM impairments were compared by functional limitations. Characteristics significantly associated with early ROM impairment (but not later impairment) were axillary lymph node dissection, removal of ≥15 nodes, mastectomy surgery and stage II breast cancer. Positive nodes, older age, and BMI≥25 were significantly associated with reduced shoulder ROM at 12+ months. At 12+ months, only 10 % of the patients experienced ROM impairments while rates of self-reported symptoms in the affected upper extremity at 12+ months were as follows: pain-49%, weakness-47.1%, numbness-55.9%, feeling tired-42.5%. The majority of patients used the affected upper extremity for reaching without limitation, but ≥35% reported limitation with household chores, carrying and lifting. Difficulty carrying and lifting could be predicted by BMI≥25 and use of the dominant affected upper limb. Different factors are associated with early versus later ROM loss. Symptoms reported by breast cancer survivors are frequently associated with functional limitations in upper extremity tasks and warrant intervention. Physical therapy using a prospective surveillance model of care may reduce severity of ROM loss, symptoms and functional upper extremity limitations 1 year after breast cancer surgery.

Factors predicting clinically significant fatigue in women following treatment for primary breast cancer.

Cancer-related fatigue is common, complex, and distressing. It affects 70-100% of patients receiving chemotherapy and a significant number who have completed their treatments. We assessed a number of variables in women newly diagnosed with primary breast cancer (BrCa) to determine whether biological and/or functional measures are likely to be associated with the development of clinically significant fatigue (CSF). Two hundred twenty-three women participated in a study designed to document the impact of the diagnosis and treatment of primary breast cancer on function. Forty-four had complete data on all variables of interest at the time of confirmed diagnosis but prior to treatment (baseline) and ≥ 9 months post-diagnosis. Objective measures and descriptive variables included history, physical examination, limb volume, hemoglobin, white blood cell count, and glucose. Patient-reported outcomes included a verbal numerical rating of fatigue (0-10, a score of ≥ 4 was CSF), five subscales of the SF-36, Physical Activity Survey, and Sleep Questionnaire. At baseline, the entire cohort (n = 223) and the subset (n = 44) were not significantly different for demographic, biological, and self-reported data, except for younger age (p = 0.03) and ER+ (p = 0.01). Forty-five percent had body mass index (BMI) ≥ 25, 52% were post-menopause, and 52% received modified radical mastectomy, 39% lumpectomy, 52% chemotherapy, 68% radiation, and 86% hormonal therapy. Number of patients with CSF increased from 1 at baseline to 11 at ≥ 9 months of follow-up. CSF at ≥ 9 months significantly correlated with BMI ≥ 25, abnormal white blood cell count, and increase in limb volume and inversely correlated with vigorous activity and physical function (p < 0.05). Fatigue increases significantly following the treatment of BrCa. Predictors of CSF include high BMI and WBC count, increase in limb volume, and low level of physical activity. These are remediable.