Reference no: EM131594398

Mildrey Silverio

According to the article, Insulin adjustments to maintain glycemic control in individuals with type 1 diabetes often lead to wide glucose fluctuations, hypoglycemia, and increased body weight. Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 (SGLT2) inhibitor, increases glucosuria and reduces hyperglycemia in individuals with type 2 diabetes. The primary objective of this study was to assess short-term safety of dapagliflozin in combination with insulin; secondary objectives included pharmacokinetic, pharmacodynamic, and efficacy parameters.

The study design is explained as a 2-week, dose-ranging, randomized, double-blind, placebo-controlled proof-of-concept study randomly assigned 70 adults with type 1 diabetes (HbA1c 7-10%), who were receiving treatment with stable doses of insulin, to one of four dapagliflozin doses (1, 2.5, 5, or 10 mg) or placebo. The insulin dose was not proactively reduced at randomization but could be adjusted for safety reasons.

In my opinion, this is a pilot study. Large-scale research projects tend to be complex, take a lot of time to design and execute, and typically require quite a bit of funding. Conducting a pilot study before hand allows a researcher to design and execute a large-scale project in as methodologically rigorous a way as possible, and can save time and costs by reducing the risk of errors or problems.

For these reasons, pilot studies are common among quantitative sociology studies, but are often used by qualitative researchers too. A pilot study is a research study conducted before the intended study. Pilot studies are usually executed as planned for the intended study, but on a smaller scale. Although a pilot study cannot eliminate all systematic errors or unexpected problems, it reduces the likelihood of making a Type I or Type II error.

Both types of errors make the main study a waste of effort, time, and money. The second study I found is named "Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study". In this study, Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry.

Reference

Henry, R. R., Rosenstock, J., Edelman, S., Mudaliar, S., Chalamandaris, A. G., Kasichayanula, S., ... & Griffen, S. C. (2015). Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes care,38(3), 412-419.

Sitbon, O., Jaïs, X., Savale, L., Cottin, V., Bergot, E., Macari, E. A., ... & Montani, D. (2014). Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. European Respiratory Journal, 43(6), 1691-1697.

Yanicsi Yong

Sympathetic overactivation, is reduced by renal denervation in drug-resistant hypertension. A similar role for renal denervation in heart failure remains unstudied, partly due to the concern about potential concomitant deleterious blood pressure reductions. This pilot study evaluated the safety of renal denervation for heart failure using an intensive follow-up protocol.

According to the study, 7 patients (mean age 69 years) with chronic systolic heart failure (mean BP on referral 112/65 mm Hg) on maximal tolerated heart failure therapy underwent bilateral renal denervation May-July 2011. Patients were admitted for pre-procedure baseline assessments and in-patient observation for 5 days following denervation. Follow-up was weekly for 4 weeks, and then monthly for 6 months.

Pilot studies represent a fundamental phase of the research process. The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a larger scale study. The roles and limitations of pilot studies are described here using a clinical trial as an example. A pilot study can be used to evaluate the feasibility of recruitment, randomization, retention, assessment procedures, new methods, and implementation of the novel intervention.

A pilot study is not a hypothesis testing study. Safety, efficacy and effectiveness are not evaluated in a pilot. Contrary to tradition, a pilot study does not provide a meaningful effect size estimate for planning subsequent studies due to the imprecision inherent in data from small samples.

Feasibility results do not necessarily generalize beyond the inclusion and exclusion criteria of the pilot design. A pilot study is a requisite initial step in exploring a novel intervention or an innovative application of an intervention. Pilot results can inform feasibility and identify modifications needed in the design of a larger, ensuing hypothesis testing study. Investigators should be forthright in stating these objectives of a pilot study.

Grant reviewers and other stakeholders should expect no more. I found another study where patients with metastatic CRC with BRAF V600 mutations were recruited to an expansion cohort at the previously determined maximum-tolerated dose of 960 mg orally twice a day.

Reference

Davies, J. E., Manisty, C. H., Petraco, R., Barron, A. J., Unsworth, B., Mayet, J., ... & Francis, D. P. (2013). First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study. International journal of cardiology, 162(3), 189-192.

Kopetz, S., Desai, J., Chan, E., Hecht, J. R., O'Dwyer, P. J., Maru, D., ... & Issa, J. P. J. (2015). Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. Journal of Clinical Oncology, 33(34), 4032-4038.