OBJECTIVES: Optimizing the clinical trial design and establishing the appropriate populations early in development are essential to substantiating a compelling value proposition. This project sought to provide an example of how a subpopulation investigation can inform early development strategy.  METHODS: US 2012 National Health and Wellness Survey data were used. Respondents with pain in the past month were included.  The distribution of work productivity (using the WPAI questionnaire) was examined and subpopulations of pain patients with particularly high or low impairment were described and compared to uncover groups with the highest likelihood of showing incremental benefit substantial enough to demonstrate value and compel funding.  RESULTS: A total of 24,215 respondents (34.0%) reported pain in the past month (mean age=49.96; 51.92% were female). Mean level of pain severity in the last week was 4.71 (SD=2.72) and mean overall work productivity loss was 22.04% (SD=27.84%). Although these variables were significantly related (r=0.45, p<0.05), a substantial percentage of people  with pain reported no work impairment (44.23%) creating a floor effect whereby regardless of the improvement in pain, no effect would be observed with respect to the ability to work. Conversely, 3.6% of people with pain reported 90% or more of their work week being impaired. Few demographic differences (age, sex) were observed between these two extremes, though those with 90%+ impairment were more likely to be obese (43.40%) versus those without any impairment (32.80%).  CONCLUSIONS: Pain severity and work productivity loss were significantly related but many of those with pain reported so little impairment that no intervention could provide a compelling proposition. However, key subgroups (e.g. those obese) reported significant impairments with a much greater likelihood of demonstrating treatment benefit. Subgroup analysis early in development can identify the most relevant patient populations and help inform clinical trial design, optimize incremental value, and drive cost effectiveness.