Protocol refinement for a diabetes pragmatic trial using the PRECIS-2 framework

Background This report describes how we refined a protocol for a pragmatic comparative effectiveness study of two models of an evidence-based diabetes shared medical appointment intervention and used the PRECIS-2 rating system to evaluate these adaptations. Methods We report primary data collected between June and August 2019, and protocol refinements completed between 2018 and 2020. Twenty-two members of the study team collaborated in protocol refinement and completed the PRECIS-2 ratings of study pragmatism. We discuss study design refinements made to achieve the desired level of pragmatism vs. experimental control for each of the nine PRECIS-2 dimensions. Study team members received training on PRECIS-2 scoring and were asked to rate the study protocol on the nine PRECIS-2 dimensions. Ratings were compared using descriptive statistics. Results In general, the PRECIS-2 ratings revealed high levels of pragmatism, but somewhat less pragmatic ratings on the categories of Delivery and Organization (costs and resources). This variation was purposeful, and we provide the rationale for and steps taken to obtain the targeted level of pragmatism on each PRECIS-2 dimension, as well as detail design changes made to a) make the design more pragmatic and b) address COVID-19 issues. There was general agreement among team members and across different types of stakeholders on PRECIS-2 ratings. Conclusions We discuss lessons learned from use of PRECIS-2 and experiences in refining the study to be maximally pragmatic on some dimensions and less so on other dimensions. This paper expands on prior research by describing actions to achieve higher levels of pragmatism and revise our protocol fit to the changed context. We make recommendations for future use of PRECIS-2 to help address changing context and other strategies for the planning of and transparent reporting on pragmatic research and comparative effectiveness research. Trial registration Clinicaltrials.gov Registration ID: NCT03590041.

283 Salvage Versus Primary Robot-Assisted Radical Prostatectomy: A Propensity-Matched Comparative Effectiveness Study from A High-Volume Tertiary Centre

Aim Salvage Robot-Assisted Radical Prostatectomy (sRARP) is a potential treatment option for locally recurrent Prostate Cancer after non-surgical primary treatment. There are minimal data comparing outcomes between propensity-matched salvage and primary Robot-Assisted Radical Prostatectomy (RARP). We compare perioperative, oncological, and functional outcomes of sRARP with primary RARP and between sRARP post-whole and focal gland therapy. Method 1:1 propensity-matched comparison of 146 sRARP with primary RARP from a cohort of 3,852 consecutive patients from a high-volume tertiary centre. Results There were no significant differences in patient characteristics between the salvage and primary RARP groups. Grade III-V Clavien-Dindo complication rates were 1.3% and 0% in the salvage and primary groups, respectively (p = 0.310). Median (IQR) follow-up was 16 (10,30) and 21 (13,33) months in the salvage and primary groups, respectively. BCR rates were 30.8% and 13.7% in the salvage and primary groups, respectively (p < 0.001). Pad-free continence rates were 79.1% and 85.4% at two years in the salvage and primary groups, respectively (p = 0.160). ED rates were 95.2% and 77.4% in the salvage and primary groups, respectively (p < 0.001). Comparing the whole gland and focal gland groups, BCR rates were 33.3% and 29.1%, respectively (p = 0.687), pad-free continence rates were 66% and 89.3%, respectively (p = 0.001), and ED rates were 98.3% and 93%, respectively (p = 0.145). Conclusions SRARP has similar perioperative but inferior oncological outcomes to primary RARP. Continence rates are similar to primary RARP, but potency is worse. Perioperative and oncological outcomes of sRARP after focal gland therapy are similar but continence outcomes are superior compared to sRARP after whole gland therapy.

Comparative Effectiveness of Methotrexate versus Methylprednisolone in Treatment Naïve Pulmonary Sarcoidosis Patients

Among those who study granulomatous diseases, sarcoidosis is of tremendous interest, not only because its cause is unknown, but also because it is still as much an enigma today as it was 150 years ago when Jonathan Hutchinson first described the cutaneous form of the disease as “livid papillary psoriasis”. This piece editorializes a comparative effectiveness study of methotrexate versus methylprednisolone in treatment naïve pulmonary sarcoidosis patients for CT-guided clinical responses and drug-related adverse events.

Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study

Objective: Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: a comparative effectiveness study (GRADE). <p>Research Design and Methods: Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic (SBP) and diastolic (DBP) BP, hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test (SEVLT), letter (LF) and animal fluency (AF) tests, and Digit Symbol Substitution Test (DSST). </p> <p>Results: Among 5,047 GRADE participants, 5,018 (99.4)% completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modeslty better DSST scores. Hypertension history was not related to cognition. </p> <p>Conclusions: In persons with type 2 diabetes with a mean duration of less than 5 years, lower LDL and statin use were related to modestly better executive cognitive function. SBP levels in the range of 120 to 139 mmHg, and DBP levels in the range of 80 to 89 mmHg, but not lower levels, were related to modeslty better executive function. These differences may not be clinically significant. </p> <p> </p>

Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study

Objective: Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: a comparative effectiveness study (GRADE). <p>Research Design and Methods: Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic (SBP) and diastolic (DBP) BP, hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test (SEVLT), letter (LF) and animal fluency (AF) tests, and Digit Symbol Substitution Test (DSST). </p> <p>Results: Among 5,047 GRADE participants, 5,018 (99.4)% completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modeslty better DSST scores. Hypertension history was not related to cognition. </p> <p>Conclusions: In persons with type 2 diabetes with a mean duration of less than 5 years, lower LDL and statin use were related to modestly better executive cognitive function. SBP levels in the range of 120 to 139 mmHg, and DBP levels in the range of 80 to 89 mmHg, but not lower levels, were related to modeslty better executive function. These differences may not be clinically significant. </p> <p> </p>