Pragmatic Estimation of Sample Size for Number of Interviews for PRO development in the 2009 FDA PRO guidance

PROs developed de novo, using the FDA guidance may involve structured patient interviews or focus groups. Qualitative Research is a methodology for eliciting and coding interviews and produces concepts or themes. These concepts are used to develop items in a PRO for use as an endpoint in Clinical trials. A convention in the field is that interviews and code/concept elicitation are considered complete when subsequent interviews produces "no new concepts" -termed "saturation". FDA reviewers frequently challenge PRO developers whether there are sufficient patient interviews to confirm that saturation is achieved after occurrence of zero new concepts. Several authors have reported that concrete criteria are need for confirming that saturation is achieved (Francis 2010, Mason 2010, Marshall 2013). I provide statistical methodology for confirming saturation, suitable for review by a regulatory authority. Type I error for saturation, may occur if further interviews elicited more concepts after first occurrence of saturation. I use published data set on code elicitation (Guest, 2006) to demonstrate that saturation may occur more than once in a sequence of interviews. I provide a statistical definition for saturation in qualitative research, that addresses regulatory concerns for PRO's developed for use as a clinical trial endpoint in a regulatory submission.