Realising the full potential of data-enabled trials in the UK: a call for action.

RATIONALE: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. APPROACH: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. REFLECTION: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. DISCUSSION: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Accelerometer-determined physical activity, mobility disability, and health.

BACKGROUND: We have a limited understanding of the objectively-determined physical activity levels among those with mobility limitations. Further, the association between objectively-measured physical activity and biomarkers among those with mobility limitations is relatively unknown. OBJECTIVE: Therefore, the primary objectives of this study were to compare accelerometer-determined physical activity levels among those with and without mobility limitations and determine if greater participation in physical activity was associated with more favorable health outcomes among those with mobility disability. METHODS: Data from the 2003-2006 NHANES were used. Mobility limitation status was self-reported; accelerometer-measured estimates of sedentary, light, and moderate-to-vigorous physical activity (MVPA) were determined; and blood samples were taken to measure various biomarkers. RESULTS: In general, adults with mobility limitations, compared to those without, engaged in more sedentary behavior and less light-intensity physical activity and MVPA. Adults with mobility limitations, had a higher BMI, waist circumference, C-reactive protein, white blood cells, neutrophil levels, triglycerides, glucose, HbA1C and homocysteine levels. If an adult were to increase their sedentary behavior by 60-min, their rate ratio for chronic disease would be expected to increase by a factor of 1.04. Similarly, for an increase of 60-min in light-intensity physical activity, the rate ratio for chronic disease would be expected to decrease by a factor of 0.95. MVPA was also significantly associated with chronic disease (RR: 0.91; 95% CI: 0.85-0.97). CONCLUSIONS: Minimizing sedentary behavior and increasing physical activity (even light-intensity) among those with mobility limitations may help to improve health outcomes.

Long-term outcomes for laparoscopic versus open resection of nonmetastatic colorectal cancer.

BACKGROUND: Skepticism prevails over the role of minimally invasive surgery in the treatment of colorectal cancer. Long-term data on the safety and efficacy of this technique remain scarce. A nonrandomized, prospective comparison of laparoscopic colorectal cancer surgery (LS) with open surgery (OS) was undertaken to evaluate long-term survival. METHODS: A total of 233 patients with nonmetastatic colorectal cancer underwent either a laparoscopic (n = 116) or an open (n = 117) potentially curative resection. Almost all patients between July 1996 and December 2002 were randomized within two consecutive trials; however, prior to this, a significant proportion of patients received open surgery. The primary endpoints were overall survival, disease-free survival, and cumulative disease recurrence. Analysis was by intention to treat. RESULTS: Median follow-up was 40 months for the LS group and 58 months for the OS group. No statistically significant difference was found between the LS and OS groups regarding overall survival (P = 0.603 for colon cancer and P = 0.841 for rectal cancer), disease-free survival (P = 0.684 for colon cancer and P = 0.625 for rectal cancer), and overall recurrence (P = 0.383 for colon cancer and P = 0.166 for rectal cancer). Cumulative recurrence rate in colon cancer favors OS (P = 0.018). In rectal cancer, this did not differ between the two treatment modalities (P = 0.965). Tumor resection margins and lymph node harvest were similar in the two surgery groups. Perioperative mortality in the LS group was also no different from the OS group (P = 0.644 for 30-day mortality and P = 0.692 for in-hospital mortality). CONCLUSION: Long-term survival data support LS as a safe, effective alternative to conventional surgery for treating potentially curative colorectal cancer. However, the higher cumulative recurrence associated with LS in the colonic cancer group needs further research into its underlying cause.