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

ITEM 5-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!