Study participants were comprised of self-identified adult patients with chronic ITP from among the membership of the Platelet Disorder Support Association (PDSA), a patient support group in the United States. Eligible study patients met the following criteria: diagnosed with chronic ITP, 18 years of age and older, and past or current experience with one or more of the most frequently used ITP treatment types: CS, IVIg, anti-D, RT, or SPL.
Survey instrument development
Accepted procedures were used to develop and field the survey instrument [22–24]. To draft the initial version, we identified ITP treatment side effects from product literature and package inserts, a review of the published medical literature, and expert clinical opinion. Upon central institutional review board approval, two patient focus groups with four and seven adults respectively with chronic ITP who met the eligibility criteria stated above, were conducted at the 2008 PDSA annual conference. The feedback of these patient focus groups was used to finalize the list of treatment side effects from the patient perspective and to ensure the clarity and accuracy of the instrument. Finally patient cognitive testing was implemented via phone interviews with three adult patients. These patients simultaneously completed the online survey while providing feedback to a trained interviewer on ease of use, clarity, and acceptance of survey content and instructions.
The survey instrument was specifically designed to collect patient self-reported data via a secure Internet portal on: (1) the types and numbers of side effects experienced during past and current treatments; (2) the level of burden, alternatively known as "bother"  or "distress", that patients' experienced with each reported side effect; and, (3) the patient-perceived impacts or limitations of their disease and its treatments on current daily functioning and treatment continuation. "Bother" is a term common among clinical researchers focused on patient health-related quality of life. Specifically, it refers to the amount of interference or negative impact an effect or condition has on a patient's well-being. "Aggregate bother" refers to overall or average level of the bother across all experienced effects among patients in receipt of the therapy of interest.
The instrument included modules for each treatment class: CS, IVIg, anti-D, RT, and SPL and an 'Other' intervention category. As part of the automatic navigation of the web-enabled survey, patients were allowed to complete only the modules for the treatments with which they had experience. Each treatment module included questions on treatment effects and associated bother for each treatment effect, as well as questions relating to duration of treatment, time since last treatment, and whether or not the patient had to stop or reduce treatment due to one or more of the reported side effects. Three questions related to patient perceived impact of disease on daily life. Several questions addressed clinical characteristics (e.g., typical low and high platelet count in the past 12 months), symptoms (e.g., wet bleeds (nose or mouth bleeds) and dry bleeds (bruising, hematomas, or petechiae) in the past 12 months), and demographic information.
Treatment side effects, if any, were ascertained via a series of closed ended questions, along with an open-ended option to document an "other" effect, which the patient then listed. Patients could specify a treatment effect that was not listed or could respond that no treatment side effects were experienced. For each selected treatment effect, the automated web-survey allowed patients to indicate their level of bother or distress for that effect, using a standard 5-point, fully anchored, Likert scale  (1 = "Not bothered at all;" 2 = "Bothered a little bit;" 3 = "Moderately bothered;" 4 = "Bothered quite a bit;" and 5 = "Extremely bothered"). To assess perceived impact of disease on daily life, patients were asked; "How much does your chronic ITP limit you in your: (a) choice of occupation or job, (b) daily activities, and (c) lifestyle." Again, with a standard 5-point, fully anchored Likert scale , patients rated their limitation due to disease in one of the following response categories: 1 = "Not limiting at all;" 2 = "Limiting a little bit;" 3 = "Moderately limiting;" 4 = "Limiting quite a bit;" and 5 = "Extremely limiting."
Upon study approval from the Abt Associates Institutional Review Board, a registered central institutional review board, and in accordance with the Declaration of Helsinki, accepted research practice [22, 24], and local laws and regulations, the instrument was fielded among patients with chronic ITP. First, patients in the PDSA were presented with an open invitation to participate. If interested, they then provided online consent as part of the web-based survey, before participating in the web-based survey data collection. The survey was conducted via an Internet portal with appropriate security. To control access to the survey and ensure patient confidentiality, each survey invitation included a unique password-protected link. A small honorarium ($20 USD) was provided to each qualifying patient completing the survey. To ensure complete data, the survey was configured to require an appropriate response to each relevant question before proceeding to the next question or step in the survey.
Descriptive analyses and independent t-tests comparing means were conducted. Ordinary Least Squares (OLS) and logistic regression analyses were performed to assess the association with aggregate bother, the need to stop or reduce treatment, and limitation on daily life. Models to evaluate the impact of effects on the need to stop or reduce treatment included the number of side effects and aggregate bother as the independent variables and the need to stop or reduce the dose (yes/no) as the dependent variable. Given that each patient had experience with a different combination of treatment types, a term was created to account for all patients in the model assessing limitation to daily life (treatment exposure (0,1) × Aggregate Bother (1-5)). Aggregate Bother was defined as a per patient weighted average of bother scores across their perceived side effects. Perceived impact or limitations imposed by chronic ITP on occupation, daily activities, and lifestyle were each assessed using OLS regression models which included terms for aggregate bother per side effect per treatment (0 = no treatment and 1-5 = bother). For all analyses, two-sided alpha levels of P < 0.05 were considered statistically significant. SAS 9.0 was used for analysis.