BackgroundClinical trials in rare diseases are more challenging than trials in frequent diseases. Small numbers of eligible trial participants, often complicated by heterogeneity among rare disease patients, hamper the design and conduct of a ‘classical’ Randomized Controlled Trial. Therefore, novel designs are developed by statisticians. However, it is important to be aware of possible design aspects that may jeopardize the feasibility of trial conduct. If the burden of participation is considered out of proportion by patients or parents, recruitment may fail or participants may drop out before trial completion. In order to maximize the chance of success of trials in small populations, it is important to know which aspects of trial design are considered important by patients.ResultsWe have interviewed all ten members of the Patient Think Tank (PTT) of the ASTERIX project, a European research consortium on methodology for clinical trials in small populations. The PTT members are rare disease patient representatives who have completed extensive training in clinical trial methodology. We have analyzed the interviews qualitatively according to Grounded Theory using a thematic analysis, and we structured the topics in four chronologically ordered themes: 1. Involvement in trial design; 2. Opinions on trial design; 3. Trial participation; 4. Phase after the trial. Our main findings are that the PTT-members recommend that patients are involved in trial design from an early stage on, and have influence on the outcomes and measurement instruments that are chosen in the trial, the length of the study, the choice of participants, and the information that is sent to potential participants. Also, according to the PTT-members, patient groups should consider setting up disease registries, placebo groups should be minimized, and more education on clinical trials is advised.ConclusionsRare disease patient representatives who have been educated about clinical trial methodology think it is important to involve patient representatives in research at an early stage. They can be of advice in trial design in such a way that the ratio of potential benefit and burden of trial participation as well as the chosen outcome measures and in- and exclusion criteria are optimized.Electronic supplementary materialThe online version of this article (10.1186/s13023-019-1002-z) contains supplementary material, which is available to authorized users.

Absolute Pitch (AP) is the ability to identify or produce isolated tones in the absence of contextual cues or reference pitches. While AP is thought to differ from other human abilities in its bimodal distribution (Takeuchi & Hulse, 1993) -either you have it or you do not -recent evidence suggests that memory for absolute pitch in a melody is actually widespread (Schellenberg & Trehub, 2003). In the current project the Dutch collection of historic audio recordings, Onder de Groene Linde (Grijp, 2008), is used as a source to explore the potential role of AP in the memory of songs transmitted in oral traditions. Since the melodies in this database are grouped by tune family and are available as sound files, they can serve as empirical support for the Absolute Pitch Memory (APM) hypothesis, predicting that these tunes are memorized and transmitted over time and geographical location based on their absolute pitch height. To this end, between-and within-tune family analyses were performed. In the between-tune family analysis, two tune families showed significant inter-recording tonic pitch consistency. The within-tune family analysis further substantialized that effect, while controlling for possible factors of variance such as gender, geographical origin, and lyrics. Together, the results are taken as empirical support that APM plays a significant role in the oral transmission of folksongs.