Building an infrastructure to support the development, conduct, and reporting of informative clinical studies: The Rockefeller University experience.

Introduction: Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of "informativeness," highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise. Methods and Results: Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies. Conclusions: We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.

The Rockefeller Team Science Leadership training program: Curriculum, standardized assessment of competencies, and impact of returning assessments.

The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar's primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development.

Vibrio cholera and V. parahaemolyticus coinfection in an oncology patient with gastroenteritis.

Vibrio-related gastroenteritis in the United States is mostly associated with the consumption of raw or improperly cooked seafood. We describe a case of a stage IV lung adenocarcinoma patient who became ill after eating crab while visiting Upstate New York. Molecular testing and culture confirmed a coinfection with V. parahaemolyticus and a nontoxigenic strain V. cholera.

Sleep problems in breast cancer survivors 1-10 years posttreatment.

ABSTRACTObjective:Sleep can affect quality of life (QoL) during cancer survivorship, and symptoms related to poor sleep can be exacerbated. We examined the prevalence, severity, and nature of subjective sleep complaints in women surviving stage I-III breast cancer who were 1-10 years posttreatment. We also examined the demographic, medical, physical, and psychosocial correlates of poor sleep in these women in order to identify the subgroups that may be most in need of intervention. METHOD: A total of 200 patients at a comprehensive cancer center who were 1-10 years posttreatment for primary stage I-III breast cancer with no evidence of disease at the time of enrollment completed a battery of questionnaires on demographics, sleep, physical symptoms, mood, cancer-specific fears, and QoL. RESULTS: The women had a mean age of 57 years (SD = 10.0), with a mean of 63.3 months (SD = 28.8) of post-cancer treatment. Some 38% of these patients were identified as having poor-quality sleep. Women with poor sleep took longer to fall asleep, had more awakenings, and acquired 2 hours less sleep per night than those with good sleep. They also had a lower QoL, greater severity of pain, more concerns about health and recurrence, and increased vasomotor symptoms (p < 0.05). Daytime sleepiness and depression were found to be not significantly correlated with sleep quality. SIGNIFICANCE OF RESULTS: Many breast cancer survivors had severe subjective insomnia, and several breast cancer survivor subgroups were identified as having members who might be most in need of sleep-improvement interventions. Addressing physical symptoms (e.g., vasomotor symptoms and pain) and providing education about the behavioral, social, environmental, and medical factors that affect sleep could result in substantial improvement in the life course of breast cancer survivors.

The Rockefeller University Clinical Scholars (KL2) Program 2006-2016.

INTRODUCTION AND METHODS: The Rockefeller Clinical Scholars (KL2) Program began in 1976 and transitioned into a 3-year Master's degree program in 2006 when Rockefeller joined the NIH Clinical and Translational Science Award (CTSA) program. The program consists of ~15 trainees supported by the CTSA KL2 award and University funds. It is designed to provide an optimal environment for junior translational investigators to develop team science and leadership skills by designing and performing a human subjects protocol under the supervision of a distinguished senior investigator mentor and a team of content expert educators. This is complemented by a tutorial focused on important translational skills. RESULTS: Since 2006, 40 Clinical Scholars have graduated from the programs and gone on to careers in academia (72%), government service (5%), industry (15%), and private medical practice (3%); two (5%) remain in training programs. 39/40 remain in translational research careers with 23 NIH awards totaling $23 million, foundation and philanthropic support of $20.3 million, and foreign government and foundation support of $6 million. They have made wide ranging scientific discoveries and have endeavored to translate those discoveries into improved human health. CONCLUSION: The Rockefeller Clinical Scholars (KL2) program provides one model for translational science training.

Polysomnographic Study of Sleep in Survivors of Breast Cancer.

STUDY OBJECTIVE: Insomnia is a frequent complaint in breast cancer patients during and after treatment. Breast cancer survivors, 1-10 years posttreatment, underwent in-lab polysomnography (PSG) to objectively define the insomnia in those patients with such a complaint. METHODS: Twenty-six breast cancer survivors (aged 39-80, mean 54.0 months posttreatment) spent 2 nights in the sleep laboratory. Sleep on Night 2 was scored for sleep stages, sleep onset latency, REM sleep onset latency, wake time, apneas and hypopneas, periodic limb movements and arousals. Subjects were allocated into 2 groups by their scores on the Pittsburgh Sleep Quality Index (PSQI): no/ mild sleep disturbance (PSQI score ≤ 9, n = 15) or moderate/ severe sleep disturbance (PSQI ≥ 10, n = 11). RESULTS: Standard PSG/EEG parameters failed to differentiate insomniacs from non-insomniacs. The single variable that distinguished the insomnia group was periodic limb movements in sleep (PLMS). PLMS were significantly correlated (r ≅ 0.7, p < 0.02) with subjective report of insomnia on PSQI and insomnia severity index. Log[Number of PLMS] was higher in the moderate/severe insomnia group (p = 0.008). Five of 11 patients in the moderate/severe insomnia group had a PLMS index ≥ 15, compared to only one of 15 patients in the none/mild insomnia group (p = 0.02). Menopausal symptoms and use of caffeine, hypnotics, and antidepressants were unrelated to insomnia severity or PLMS. CONCLUSIONS: PLMS was the sole PSG variable that separated breast cancer survivors with moderate/severe insomnia from those with no/mild sleep disturbance. Further study of the incidence and significance of PLMS in breast cancer survivors with the complaint of insomnia is merited.