Developing a Phase II RCT: The effects of n-3 fatty acids on lung and systemic inflammation in patients with acute lung injury Renee Stapleton 7/07/05

Outline Choosing a research question and selecting study design Process of designing the trial Timeline Budget Lessons learned

Choosing a Research Question 1.What types of clinical questions do I enjoy the most?  Supportive care mechanisms in the ICU 2.What methods do I want to focus on?  Obtain training as a clinical trialist 3.Which particular areas of ICU care need championing?  Nutritional delivery and supplementation

Choosing a Research Question 4.Is there a means to do a small trial feasibly?  ALI “Clinical Trials Incubator Unit” (CTIU) 5.Under the umbrella of nutrition and ALI, are there any questions that have a high chance of offering me early success?  Fish oil in acute lung injury (ALI)

Designing the Trial CTIU established for phase II “proof of concept” trials in ALI Details to think about –2 arms versus 3 arms –Endpoints Primary and secondary –Sample size calculations Accurate pilot data? –Enough patients at Harborview alone? –Inclusion and exclusion criteria

Designing the Trial Details to think about (continued) –Intervention Where to get the fish oil? How to deliver it? Dose? Need to do independent testing of product Do we need to submit an IND to the FDA? –Placebo –Blinding How to successfully achieve blinding?

Designing the Trial Details to think about (continued) –Identification, enrollment, and consent of patients Who will do it? When? –Randomization Who will do it? When? What design?

Designing the Trial Details to think about (continued) –Adverse effects –“Cointerventions” Need to standardize other practices that may affect outcome –Collecting and managing data How to ensure accuracy? Missing data –Statistical analyses

The Final Design 100 patients with ALI 1/3 fish oil + enteral nutrition 1/3 placebo + enteral nutrition 1/3 Oxepa® Enrollment and randomization within 48 hours of ALI diagnosis Bronchoalveolar lavage and serum sampling at study entry and on days 5 and 10 (primary outcome is BAL IL-8) Study drug delivered through day 10, extubation, or death Secondary outcomes recorded for use in designing future trial

Timeline February 2004 – Idea was conceived June 2004 – Started writing K23 October 2004 – Submitted K23 March 2005 – K12 funding July 2005 – Human subjects application January 2006 – Begin enrollment December 2007 – End of enrollment?

Budget CTIU already pays for –Full time research nurse –Full time laboratory tech –Some laboratory support for assays K12 pays for –My salary –Travel to national meeting –Desktop computer and software –Biostatistical consultation

Budget – My Costs ITEM5-YEAR COST 0.25 FTE research nurse$87,500 Pharmacy (IDS) costs for fish oil product, packaging, and randomization $43,345 Lab assays$43,390 Oxepa® enteral feeding formula$23,680 Laptop computer and printer$3,000 Travel to Toronto and Kingston, Ontario$10,000 Sample banking/storage$10,000??? Total$220,915

Lessons Learned Start early Designing the trial and getting funded is hard… Rumor is that conducting and managing the trial is HARDER! We’ll see

Mmmm, sausage!