For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel therapeutics to treat rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat cancer and infectious diseases like HIV.In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel surrogate endpoint. The application of AA to rare diseases requires more predictability to drive greater access to appropriate use of AA for more rare disease treatments that might not be developed otherwise.This white paper proposes a scientific framework for assessing biomarker endpoints to enhance the development of novel therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in rare disease programs; 2) Implementing a Biomarker Qualification Request Process to provide the opportunity for an early determination of biomarker acceptance; and 3) A proposed scientific framework for qualifying biomarkers as primary endpoints. The paper’s final section highlights case studies of successful examples that have incorporated biomarker endpoints into FDA approvals for rare disease therapies. The focus of this paper is on the situation in the Unites States, but the recommendations are reasonably applicable to any jurisdiction.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0195-4) contains supplementary material, which is available to authorized users.

recent years, the relationship between orality and writing has become one of the most important areas in the study of the European Middle Ages. Historians have reached a broad consensus that oral and written traditions complemented one other to varying degrees from the ninth through the twelfth centuries. Written documents supported or reinforced ongoing oral traditions without replacing them, and oral communication played a central role even in highly literate communities.' Much scholarship on orality and literacy emphasizes the increased importance of written and literate modes in the Carolingian period and the high Middle Ages; historians of Western music have focused most closely on the interplay of oral and written transmission in the ninth and tenth centuries. With regard to the earliest surviving examples of Western musical notation, the importance of orality may have been overstated.2 A more fruitful approach would interpret the function and context of

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Medieval monastic Psalters attest to the central role of the psalms as living texts in religious communities, where the psalms were experienced both through constant liturgical performance and through reading the commentary traditions (such as the Christian tituli psalmorum and glosses) transmitted with the psalms in many manuscripts of the central Middle Ages. 1 Besides these texts, medieval monastic Psalters often contained office chants, computus, abbreviated Psalters, and collections of prayers for various purposes. Although modern scholarship frequently separates the elements of such books into several discrete categories, in combination these components constitute a rich ensemble of resources for monastic prayer in all its manifestations. Studying the monastic Psalters of the central Middle Ages as integrated collections brings out fundamental connections between the performance of the monastic liturgy and those prayers that scholars usually characterize as devotional.Historians of medieval religion have increasingly demonstrated that any consistent distinction between liturgy as a category of practices performed only in public and devotion as predominantly private is elusive indeed. 2 Although differences between the two are a matter of opinion, in this study I use the term "liturgy" to designate acts of structured communal worship (such as the Mass, Office, processions, and other ceremonies in which clergy preside) and "devotion" to refer to more flexible practices that can be performed by an individual and do not involve clergy. 3 Of course, such terms operate in a continuum of practice variable I am grateful to Rachel Fulton, Louis Hamilton, Roy Hammerling, and the anonymous readers for Speculum for their comments on earlier versions of this article.1 Among the many studies of psalmody in the monastic life see particularly three articles by Joseph Dyer: "Monastic convincingly for a broader usage of the word "liturgy." 896Speculum 82 (2007) Prayer as Liturgical Performance 897 across time and place; they designate fluid parameters rather than firm categories. An individual could experience the liturgy as a personal devotion, and prayers that were evidently intended for individuals to recite can be liturgically structured. 4 Particularly when studying medieval monastic communities, in which daily life was articulated around prayer, boundaries between categories of "public" liturgical worship and "private" devotion are fluid. Monastic Psalters of the central Middle Ages contain some prayers so profoundly shaped by liturgical performance that they cannot be entirely separated from the Divine Office. The hours of psalmody sung in monasteries daily constituted a deeply ingrained practice that informed ways of thinking and praying. Like the monastic garment, the liturgy was a habit that could not be shed, a fundamental and underlying condition of life in a religious community. 5 Situating the prayers found in monastic Psalters of the eleventh and twelfth centuries within the spectrum of liturgical performa...