@article{8249dc086c3341eeb23870213d5d2ea9,
title = "PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy",
abstract = "Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older. The many areas of investigation and rationale for each are discussed by organ systems, along with recognition of remaining important questions that will not be addressed by this study alone. Knowledge gained through this and multiple complementary studies around the world will help to understand important health outcomes, clinical care priorities, and research needs for a large majority of people treated with these or similarly effective medications targeting the primary cellular impairment in cystic fibrosis.",
keywords = "Cftr, Clinical trial, Cystic fibrosis, Drug, Elexacaftor, Ivacaftor, Modulator, Promise, Tezacaftor",
author = "Nichols, {Dave P.} and Donaldson, {Scott H.} and Frederick, {Carla A.} and Freedman, {Steven D.} and Daniel Gelfond and Hoffman, {Lucas R.} and Andrea Kelly and Narkewicz, {Michael R.} and Pittman, {Jessica E.} and Felix Ratjen and Sagel, {Scott D.} and Margaret Rosenfeld and Schwarzenberg, {Sarah Jane} and Singh, {Pradeep K.} and Solomon, {George M.} and Stalvey, {Michael S.} and Shannon Kirby and VanDalfsen, {Jill M.} and Clancy, {John P.} and Rowe, {Steven M.}",
note = "Funding Information: Clinical care and research in cystic fibrosis (CF) have been heavily influenced by the emergence of highly effective modulator drug therapies (HEMT) that target the CF transmembrane conductance regulator protein (CFTR). These CFTR modulators increase CFTR function by improving the processing, trafficking, and gating of aberrant proteins in the cell. Results show that CFTR modulators significantly, and at times dramatically, improve health outcomes and quality of life [ 1 , 2 ]. Herein we highlight a breadth of observational research studies now being conducted to understand the impact of HEMT regimens across a spectrum of disease manifestations. This work is organized within the PROMISE study (NCT04038047) in the United States and sponsored by the Cystic Fibrosis Foundation, independent of the manufacturer. Nearly 700 individuals will ultimately participate to contribute prospective research visits through 2 years of elexacaftor/tezacaftor/ivacaftor (ETI) treatment. This is similar to other recent post-approval trials (i.e. GOAL; NCT01521338, PROSPECT; NCT02477319), but PROMISE will expand upon key questions that have arisen in the modulator era. In the spirit of multi-disciplinary coordination, 8 sub-studies within PROMISE will be conducted by specialty experts. We describe below the rationale, objectives, and deliverables, while highlighting key questions that will remain to be addressed by further research and other investigative efforts (e.g. RECOVER; NCT04602468, BEGIN; NCT04509050) equally important in understanding the future for PwCF treated with modulators. This is a unique and time sensitive opportunity to understand how effective CFTR restoration alters the disease state as a large majority of PwCF begin HEMT. PROMISE, as one of several studies being conducted within the US CF Therapeutics Development Network (TDN), will broadly clarify remaining needs and priorities for clinical care and research in individuals with CF treated with HEMT. As with similar other studies supported by the CF Foundation and conducted in the TDN, upon study completion and publication of primary study results, de-identified datasets will be available through the CFF TDN Data Archive. Researchers may apply to the CF TDN for use of de-identified data from the archive for research purposes, and must receive appropriate IRB approval before data is sent from the Archive. In PROMISE, biospecimens are also being aliquoted and carefully preserved for future investigator-initiated requests through the centralized CF Foundation Biorepository. When approved, these samples can be linked with de-identified data from the Archive. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = mar,
doi = "10.1016/j.jcf.2021.02.003",
language = "English",
volume = "20",
pages = "205--212",
journal = "Journal of Cystic Fibrosis",
issn = "1569-1993",
number = "2",
}