Development and Content Validity of a Novel Myelodysplastic Syndromes Symptom Daily Diary

Background

Myelodysplastic syndromes (MDS) are associated with the reduction in healthy blood cells produced in the bone marrow, which subsequently lead to a variety of symptoms. A review of existing patient-reported outcome (PRO) questionnaires used in MDS or acute myeloid leukemia found that few if any were developed to measure symptoms of higher-risk MDS in the context of clinical trials. An MDS symptom daily diary has been developed following conduct of a targeted review of peer-reviewed literature and advice meetings with three clinical experts who treat patients with higher-risk MDS. The primary goal of this study was to evaluate the content validity of the novel MDS symptom daily diary among adults with higher-risk MDS.

Methods

Qualitative interviews were conducted via telephone with 15 adults with higher-risk MDS. The interviews were composed of two parts. During the concept elicitation portion, participants were asked to spontaneously describe their experience of higher-risk MDS, with particular focus on the symptoms they experience and the impact on their lives. Participants then completed the MDS symptom daily diary and provided feedback on the instructions, items, and response options in order to evaluate its readability, comprehensibility, relevance, and comprehensiveness. Interviews were conducted in three waves. Following each wave, developers reviewed summaries of results based on detailed interviewer notes. Revisions to the daily diary were made based on interim results prior to the next wave of interviews. Following the completion of all interviews, audio-recordings of the interviews were transcribed, coded, and analyzed.

Results

A total of 15 participants (53.3% female, ages 36 - 81 [mean=66, standard deviation=11.3] years) completed an interview: 7 in Wave 1, 3 in Wave 2, and 5 in Wave 3. All had begun treatment with a hypomethylating agent within six months prior to screening or were treatment-naïve. Participants reported experiencing 20 different symptoms of higher-risk MDS; the most frequently reported symptoms were fatigue (n = 13, 86.6%), bruising (n = 11, 73.3%), shortness of breath (n = 11, 73.3%), lack of energy (n = 10, 66.6%), heaviness in the arms or legs (n = 9, 60.0%), weakness (n = 9, 60.0%), bleeding (n = 8, 53.3%), and bone pain (n = 4, 26.6%). Participants identified fatigue and lack of energy as the most bothersome symptoms and the most important to improve with treatment.

Based upon participant feedback in Wave 1, two items were removed from the draft diary due to their overlap with other items. Additionally, one item was revised for clarity. Following Wave 2, a single item to assess shortness of breath was retained while alternate items assessing shortness of breath were removed based on participant feedback. No further revisions to the diary were made based on participant feedback in Wave 3.

The final version of the MDS symptom daily diary consists of eight items assessing fatigue, weakness, lack of energy, shortness of breath, bruising, bleeding, bone pain, and heaviness in arms or legs. All participants interpreted the instructions, items, and response options as intended by the developers. Participants found the diary easy to complete and relevant to their experience, and no participants suggested removing any items from the final version.

Conclusion

The MDS symptom daily diary has been developed as a tool to characterize the symptom burden of MDS and to evaluate the efficacy of study medications in clinical trials. The qualitative interviews provide evidence of its content validity; in future research, the psychometric properties of the daily diary and interpretation of its scores will be evaluated using data from an upcoming Phase 3 clinical trial.