Margaret Rosenfeld, MD, MPH

Pulmonary and Sleep Medicine, Cystic Fibrosis Research

On staff since May 1995

Children's Title: Director, Clinical Research Scholars Program; Associate Director, Center for Clinical and Translational Research

Academic Title: Professor, Department of Pediatrics

Research Center: Center for Clinical and Translational Research

  • Margaret Rosenfeld, MD, MPH, is attending physician at Seattle Childrens Hospital and Professor in the Department of Pediatrics at the University of Washington School of Medicine. Her clinical interests focus on the diagnosis and management of respiratory illnesses in children of all ages, working closely with families. Her research program focuses on NIH and foundation-sponsored multicenter observational and interventional studies in pediatric chronic lung diseases, including cystic fibrosis and primary ciliary dyskinesia. She also conducts research on mobile health tools for respiratory diseases in low resource settings.

    She is also an investigator in a national network investigating rare disorders of mucociliary clearance, including primary ciliary dyskinesia. She is director of the Clinical Research Scholars Program, codirector of the Seattle Childrens Fellows College. She serves as CF consultant to the Washington State Newborn Screening Program.

    • Chelsea Bothell, WA 09.13.17

      We met with Dr. Rosenfeld to follow up after our toddler's recent admission for Reactive Airway Disease. She was warm, knowledgeable, and spent plenty of time with us answering our questions. She validated our concerns/fears and gave us good insight into his condition. We felt confidence in the plan of action after the appointment. We feel really grateful to have her as part of our son's medical team.

    • Ellisa Chehalis, WA 03.21.11

      We first saw Dr. Rosenfeld when our child was very young, around 4 months old. We were seeing her to determine if our child had PCD. She was very caring, thourough, and was willing to sit and answer all our questions as long as we needed. She has continued caring for our child, who is now 2. We are so greatful to have such a knowledgable Doctor taking care of our child and helping us prevent future health problems and research this rare pulmonary disorder. We highly recommend her. Ellisa Alderson

  • Award Name Award Description Awarded By Award Date
    Finalist, UW School of Medicine Mentoring Award 2013
    Finalist, UW School of Medicine Mentoring Award 2010
    Physician Scientist Fellowship Award Glaxo Corporation 1993
    Leroy Matthews Physician Scientist Award Cystic Fibrosis Foundation 1992 - 1998
  • Manuscripts in Refereed Journals

    • Fink AK, Graff G, Byington CL, Loeffler DR, Rosenfeld M, Saiman L. Palivizumab and Long-term Outcomes in Cystic Fibrosis.
      Palivizumab and Long-term Outcomes in Cystic Fibrosis
      Pediatrics, 2019
    • Ratjen F, Davis SD, Stanojevic S, Kronmal RA, Hinckley Stukovsky KD, Jorgensen N, Rosenfeld M; SHIP Study Group
      Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial.
      Lancet Respir Med, 2019
    • Sanders DB, Ostrenga JS, Rosenfeld M, Fink AK, Schechter MS, Sawicki GS, Flume PA, Morgan WJ
      Predictors of pulmonary exacerbation treatment in cystic fibrosis.
      J Cyst Fibros, 2019
    • Rosenfeld M, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Chilvers M, Higgins M, Tian S, Cooke J, Davies JC; KLIMB study group
      An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB).
      J Cyst Fibros, 2019
    • M. Rosenfeld, S. Cunningham, W.T. Harris, et al
      An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2–5 years (KLIMB)
      Journal of Cystic Fibrosis, 2019
    • Davis SD, Rosenfeld M, Lee HS, Ferkol TW, Sagel SD, Dell SD, Milla C, Pittman JE, Shapiro AJ, Sullivan KM, Nykamp KR, Krischer JP, Zariwala MA, Knowles MR, Leigh MW; and Genetic Disorders of Mucociliary Clearance Consortium
      Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.
      Am J Respir Crit Care Med, 2018
    • Chi DL, Rosenfeld M, Manci L, Chung WO, Presland RB, Sarvas E, Rothen M, Alkhateeb A, McNamara S, Genatossio A, Virella-Lowell I, Milla C, Scott J
      Age-related heterogeneity in dental caries and associated risk factors in individuals with cystic fibrosis ages 6-20 years: A pilot study
      J Cyst Fibros, 2018
    • Mayer-Hamblett N, Retsch-Bogart G, Kloster M, Accurso F, Rosenfeld M, Albers G, Black P, Brown P, Cairns A, Davis S, Graff G, Kerby G, Orenstein D, Buckingham R, Ramsey B, for the OPTIMIZE Study Group
      Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis: The Optimize Randomized Trial
      Annals of the American Thoracic Society, 2018
    • Shapiro AJ, Davis SD, Polineni D, Manion M, Rosenfeld M, Dell SD, Chilvers MA, Ferkol TW, Zariwala MA, Sagel SD, Josephson M, Morgan L, Yilmaz O, Olivier KN, Milla C, Pittman JE, Daniels MLA, Jones MH, Janahi IA, Ware SM, Daniel SJ, Cooper ML, Nogee LM, Anton B, Eastvold T, Ehrne L, Guadagno E, Knowles MR, Leigh MW, Lavergne V
      Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline.
      Am J Respir Crit Care Med, 2018 : e24-e39
    • Rosenfeld M, Wainwright CE, Higgins M, Wang LT, McKee C, Campbell D, Schneider J, Cunningham S, Davies JC, ARRIVAL study group
      Ivacaftor treatment in children 12 to <24 months old with cystic fibrosis and a CFTR gating mutation: results from the a phase 3 single-arm study
      Lancet Respir Med, 2018 : 30202-9
    • Rosenfeld M, VanDevanter DR, Ren CL, Elkin EP, Pasta DJ, Konstan MW, Morgan WJ
      Decline in Lung Function Doest not Predict Future Decline in Lung Function in Cystic Fibrosis Patients
      Pediatr Pulmonol, 2018
    • Ratjen F, Klingel M, Black P, Powers MR, Grasemann H, Solomon M, Sagel SD, Donaldson SH, Rowe SM, Rosenfeld M
      Changes in Lung Clearance Index in Preschool Cystic Fibrosis Patients Treated with Ivacaftor
      Am J Respir Crit Care Med, 2018
    • Robinson PD, Latzin P, Ramsey KA, Stanojevic S, Aurora P, Davis SD, Gappa M, Hall GL, Horsley A, Jensen R, Lum S, Milla C, Nielsen KG, Pittman JE, Rosenfeld M, Singer F, Subbarao P, Gustafsson PM, Ratjen F
      ATS Assembly on Pediatrics. Preschool Multiple-Breath Washout Testing. An Official American Thoracic Society Technical Statement
      Am J Respir Crit Care Med, 2018
    • Cogen JD, Onchiri F, Emerson J, Gibson RL, Hoffman LR, Nichols DP, Rosenfeld M
      Chronic Azithromycin Use in Cystic Fibrosis and Risk of Treatment-Emergent Respiratory Pathogens
      Ann Am Thorac Soc, 2018
    • Edwards TC, Emerson J, Genatossio A, McNamara S, Onchiri F, Goss C, Patrick DL, Rosenfeld M
      Development and Pilot Testing of Observer-Reported Outcomes (ObsROs) for Children with Cystic Fibrosis Ages 0-11 Years
      J Cyst Fibros, 2018
    • Sawicki GS, Ostrenga J, Petren K, Fink AK, D'Agostino E, Strassle C, Schechter MS, Rosenfeld M
      Risk Factors for Gaps in Care during Transfer from Pediatric to Adult Cystic Fibrosis Programs in the United States.
      Ann Am Thorac Soc, 2017
    • Culver B, Graham B, Coates A, Wanger J, Berry C, Clarke P, Hallstrand T, Hankinson J, Kaminsky D, MacIntyre N, McCormack M, Rosenfeld M, Stanojevic S, Weiner D
      Recommendations for a Standardized Pulmonary Function Report - An ATS Technical Statement
      Am J Resp Crit Care Med , 2017 : 1463-1472
    • Heltshe SL, Khan U, Beckett V, Baines A, Emerson J, Sanders DB, Gibson RL, Morgan W, Rosenfeld M
      Longitudinal development of initial, chronic and mucoid Pseudomonas aeruginosa infection in young children with cystic fibrosis.
      J Cyst Fibros, 2017
    • Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S, Milla CE, Robinson PD, Waltz D, Davies JC; VX14-809-109 investigator group; Rosenfeld M
      Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial
      Lancet Respir Med, 2017 : 557-567
    • Psoter KJ, DeRoos AJ, Wakefield J, Mayer J, Rosenfeld M
      Air pollution exposure is associated with MRSA acquisition in young U.S. children with cystic fibrosis
      BMC Pulm Med, 2017 : 106
    • Psoter KJ, De Roos AJ, Wakefield J, Mayer JD, Rosenfeld M
      Seasonality of acquisition of respiratory bacterial pathogens in young children with cystic fibrosis
      BMC Infect Dis, 2017 : 411
    • Otjen JP, Swanson JO, Oron A, DiBlasi RM, Swortzel T, Van Well J, Gommers E, Rosenfeld M
      Spirometry-assisted HRCT in children: Is it worth the effort? Current Problems in Diagnostic Radiology
      Curr Probl Diagn Radiol, 2017 : 30164-5
    • Cogen J, Oron A, Gibson RL, Hoffman L, Kronman M, Ong T, Rosenfeld M
      Characterization of Inpatient Cystic Fibrosis Pulmonary Exacerbations
      Pediatrics, 2017 : 139(2)
    • Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, Howenstine M, McColley SA, Rock M, Rosenfeld M, Sermet-Gaudelus I, Southern KW, Marshall BC, Sosnay PR
      Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation
      J Pediatr, 2017
    • Ong T, Schechter M, Yang J, Peng L, Emerson J, Gibson RL, Morgan W, Rosenfeld M for the EPIC Study Group
      Socioeconomic Status and Environmental Tobacco Smoke Impact on Lung Outcomes in Cystic Fibrosis
      Pediatrics, 2017 : 139(2)
    • Farrell PM, White TB, Howenstine MS, Munck A, Parad RB, Rosenfeld M, Sommerburg O, Accurso FJ, Davies JC, Rock MJ, Sanders DB, Wilschanski M, Sermet-Gaudelus I, Blau H, Gartner S, McColley SA
      Diagnosis of Cystic Fibrosis in Screened Populations
      J Pediatr , 2017
    • Leigh MW, Ferkol TW, Davis SD, Lee HS, Rosenfeld M, Dell SD, Sagel SD, Milla C, Olivier KN, Sullivan KM, Zariwala MA, Pittman JE, Shapiro AJ, Carson JL, Krischer J, Hazucha MJ, Knowles MR
      Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents.
      Ann Am Thorac Soc, 2016 : 1305-13
    • Lahiri T, Hempstead SE, Brady C, Cannon C, Clark K, Condren ME, Guill MF, Guillerman RP, Leone CG, Maguiness K, Rosenfeld M, Schwarzenberg SJ, Tompkins CL, Zemanick ET, Davis SD
      Clinical Practice Guidelines for Preschoolers with Cystic Fibrosis
      Journal of Pediatrics, 2016 : 137(4)
    • Leigh MW, Ferkol TW, Davis SD, Lai HS, Rosenfeld M, Dell SD, Sagel SD, Milla C, Olivier KN, Sullivan KM, Zariwala MZ, Pittman J, Shapiro AJ, Corson JS, Krischer J, Hazucha M, Knowles M
      Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents
      Ann Am Thoracic Society, 2016
    • Shapiro AJ, Zariwala MA, Ferkol T, Davis SD, Sagel SD, Dell SD. Rosenfeld M, Olivier KN, Milla C, Daniel SJ, Kimple AJ, Manion M, Knowles MR, Leigh MW
      Diagnosis, Evaluation, and Treatment of Primary Ciliary Dyskinesia:PCD Foundation Consensus Recommendations Based on State of the Art Review
      Pediatric Pediatr Pulmonol, 2016 : 115-32
    • Davies, JC, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GW, Southern KW, Robertson S, Green Y, Cooke J, Rosenfeld M
      An Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Patients Aged 2 to 5 Years with Cystic Fibrosis from a CFTR Gating Mutation: The KIWI Study
      Lancet Respir Med, 2016 : 107-15
    • Peterson-Carmichael S, Seddon P, Cheifetz I, Frerichs I, Hall GL, Hammer J, Hantos Z, van Kaam AH, McEvoy CT, Newth CJL. Pillow JJ, Rafferty GF, Rosenfeld M, Stocks J, Ranganathan S
      An Official ATS/ERS Workshop Report: Evaluation of Respiratory Mechanics and Function in the Pediatric and Neonatal Intensive Care Units
      Ann Am Thorac Soc, 2016 : S1-S11
    • Davis SD, Ratjen F, Brumback LC, Johnson RC, Filbrun AG, Kerby GS, Panitch HB, Donaldson SH, Rosenfeld M
      Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis
      J Cyst Fibros, 2015
    • Psoter KJ, De Roos AJ, Wakefield J, Mayer JD, Bryan M, Rosenfeld M
      Association of meteorologic and geographic factors and risk of initial Pseudomonas aeruginosa acquisition in young children with cystic fibrosis
      Association of meteorologic and geographic factors and risk of initial Pseudomonas aeruginosa acquisition in young children with cystic fibrosis, 2015 : 1-9
    • Sanders DB, Fink A, Mayer-Hamblett N, Schechter MS, Sawicki GS, Rosenfeld M, Flume PA, Morgan WJ
      Early Life Growth Trajectories in Cystic Fibrosis are Associated with Pulmonary Function at Age 6 Years
      J Pediatr, 2015
    • Sanders DB, Emerson J, Ren C, Schechter MS, Gibson RL, Morgan W, Rosenfeld M for the EPIC Study Group
      Early childhood risk factors for decreased FEV1 at age 6-7 years in young children with cystic fibrosis
      Ann Am Thorac Soc, 2015 : 1170-6
    • Ren C, Fink A, Petren K, Borowitz D, McColley S, Rosenfeld M, Sanders D, Marshall B
      Outcomes of Infants with Indeterminate Diagnosis Detected by Cystic Fibrosis Newborn Screening
      Pediatrics, 2015 : 2014-3698
    • Subbarao P, Milla C, Aurora P, Davies J, Davis S, Hall G, Heltshe S, Latzin P, Linblad A, Pittman J, Robinson P, Rosenfeld M, Singer F, Starner T, Ratjen F, Morgan W
      Multiple Breath Washout as a Lung Function Test in Cystic Fibrosis: Ready for Prime Time?
      Ann Am Thorac Soc, 2015 : 932-9
    • Cogen J, Sanders DB, Ren C, Schechter M, Emerson J, Gibson R, Morgan W, Rosenfeld M for the EPIC Study Group
      Risk factors for lung function decline in a large cohort of young cystic fibrosis patients
      Pediatr Pulmonol, 2015 : 763-70
    • Schechter MS, Regelmann W, Sawicki GS, Rasouliyan L, VanDeVanter DR, Rosenfeld M, Pasta D, Morgan W, Konstan MW
      Antibiotic treatment of pulmonary exacerbations: a comparison by care site
      Pediatr Pulmonol, 2015 : 431-40
    • Psoter KJ, De Roos AJ, Mayer JD, Kaufman JD, Wakefield J, Rosenfeld M
      Fine particular matter exposure and initial Pseudomonas aeruginosa acquisition in cystic fibrosis
      Ann Am Thorac Soc, 2015 : 385-91
    • Davis SD, Ferkol TW, Rosenfeld M, Lee HS, Dell SD, Sagel SD, Milla C, Zariwala MA, Pittman JE, Shapiro AJ, Carson JL, Krischer JP, Hazucha MJ, Cooper ML, Knowles MR, Leigh MW
      Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype
      Am J Respir Crit Care Med, 2015 : 316- 24
    • Zemanick ET, Emerson J, Thompson V, McNamara Sh, Morgan W, Gibson RL, Rosenfeld M for the EPIC Study Group
      Clinical outcomes after initial Pseudomonas acquisition in cystic fibrosis
      Pediatric Pulmonology, 2015 : 42-8
    • Mogayzel PJ Jr, Naureckas ET, Robinson KA, Brady C, Guill M, Lahiri T, Lubsch L, Matsui J, Oermann CM, Ratjen F, Rosenfeld M, Simon RH, Hazle L, Sabadosa K, Marshall BC
      Cystic Fibrosis Foundation Pulmonary Clinical Practice Guidelines Committee. Cystic Fibrosis Foundation pulmonary guideline. pharmacologic approaches to prevention and eradication of initial Pseudomonas aeruginosa infection.
      Ann Am Thorac Soc, 2014 : 1640-50
    • Alpern AN, Brumback LC, Ratjen F, Rosenfeld M, Davis SD, Quittner AL
      Initial validation of the Parent Cystic Fibrosis Questionnaire-Revised (CFQ-R) in infants and young children. Journal of Cystic Fibrosis
      Journal of Cystic Fibrosis , 2014
    • Mayer-Hamblett N, Ramsey BW, Kulasekara HD, Wolter DJ, Houston LS, Pope CE, Kulasekara BR, Armbruster CR, Burns JL, Retsch-Bogart G, Rosenfeld M, Gibson RL, Miller SI, Khan U, Hoffman LR
      Pseudomonas aeruginosa phenotypes associated with eradication failure in children with cystic fibrosis
      Clin Infect Dis , 2014 : 624-31
    • Daines C, VanDeVanter D, Khan U, Emerson J, Heltshe S, McNamara S, Anstead M, Langkamp M, Doring G, Ratjen F, Ramsey B, Gibson RL, Morgan W, Rosenfeld M; EPIC Investigators
      Serology as a diagnostic tool for predicting initial Pseudomonas aeruginosa acquisition in children with cystic fibrosis
      J Cyst Fibros , 2014 : 542-9
    • Mayer-Hamblett N, Rosenfeld M, Gibson RL, Ramsey BW, Kulasekara HD, Retsch-Bogart GZ, Morgan W, Wolter DJ, Pope CE, Houston LS, Kulasekara BR, Khan U, Burns JL,Milller SI, Hoffman LR
      Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes
      Am J Respir Crit Care Med, 2014 : 289-97
    • Psoter KJ, Rosenfeld M, De Roos AJ, Mayer JD, Wakefield J
      Differential Geographical Risk of Initial Pseudomonas aeruginosa Acquisition in Young U.S. Children with Cystic Fibrosis
      American Journal of Epidemiology , 2014 June : 1503-13
    • Stanojevic, S., Stocks, J., Bountziouka, V,. Aurora, P., Kirkby, J., Bourke, S., Carr, S.B., Gunn, E., Prasad, A., Rosenfeld, M., Bilton, D
      The Impact of switching to the new Global Lung Function Initiative Equations on Spirometry Results in the UK CF Registry
      Journal of Cystic Fibrosis, 2014 May : 319-27
    • Brumback LC, Baines A, Ratjen F, Davis SD, Daniel SL, Quittner AL, Rosenfeld M; for the ISIS Study Group
      Pulmonary exacerbations and parent-reported outcomes in children <6 years with cystic fibrosis.
      Pediatr Pulmonol, 2014
    • Leigh MW, Hazucha MJ, Chawla KK, Baker BR, Shapiro AJ, Brown DE, Lavange LM, Horton BJ, Qaqish B, Carson JL, Davis SD, Dell SD, Ferkol TW, Atkinson JJ, Olivier KN, Sagel SD, Rosenfeld M, Milla C, Lee HS, Krischer J, Zariwala MA, Knowles MR; the Genetic Disorders of Mucociliary Clearance Consortium
      Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia
      12406843 Ann Am Thorac Soc, 2013 Dec. : 574-81

  • Presentations Title Event Location Date
    Digital health monitoring: Beyond heart rates and pedometers Association for Women in Science 30th anniversary meeting Seattle, WA Feb. 18, 2015
    Home spirometry: whats on the horizon North American Cystic Fibrosis Conference Atlanta, GA Oct. 2014
    Clinical trials in preschool children with CF European Cystic Fibrosis Conference Gothenburg, Sweden June 14, 2014
    Survey of clinical infant lung function testing practices. International Symposium on Respiratory Disease Shanghai, China Nov. 9, 2013
    Early CF Lung Disease: Diagnosis, Treatment and Prevention Duke University School of Medicine Nov. 28, 2012
    Pulmonary Exacerbation as a Clinical Trial Endpoint: The Pros and Cons North American CF Conference Orlando, FL Oct. 2012
    Designing Investigator Initiated Trials Presentation In symposium "Multidisciplinary Approach to Investigator-initiated Trials," North American CF Conference Orlando, FL Oct. 2012
    Pulmonary and Nutritional Consequences of CF in the First 6 Years of Life presentation in symposium "After the Newborn Screen: What to Do Next?" North American CF Conference Orlando, FL Oct. 2012
    What lung function test is best for managing young children with CF talk in session "Is it time to bring pre-school lung function testing to the clinic? Update from the ATS/ERS Task Force" European Respiratory Society Congress Vienna, Austria Sept. 2012
    Writing Your First Grant ITHS career development series, University of Washington Seattle, WA Oct. 30, 2009
    Successful Transition to an Academic Career half-day SCH Fellows’ College workshop unknown Oct. 28, 2009
    Risk factors for early age at acquisition of Pseudomonas aeruginosa North American Cystic Fibrosis Conference Minneapolis, MN Oct. 17, 2009
    Newborn screening North American Cystic Fibrosis Conference Minneapolis, MN Oct. 17, 2009
    Pulmonary Exacerbations: How do we define them Symposium presentation, North American Cystic Fibrosis Conference Minneapolis, MN Oct. 16, 2009
    Comparison of published pulmonary exacerbation definitions Cystic Fibrosis Foundation Workshop on Pulmonary Exacerbations Bethesda, MD Sept. 9, 2009
    Guidelines for Care of theGuidelines for Care of the Infant with CF Infant with CF Cystic Fibrosis annual Northwest regional conference, Center for Urban Horticulture unknown July 24, 2009
    Risk factors for early Pseudomonas acquisition Cystic Fibrosis Epidemiology/Biostatistics Working Group annual meeting, Center for Urban Horticulture unknown July 23, 2009
    Optimal lung function tests for monitoring cystic fibrosis, bronchopulmonary dysplasia and recurrernt wheezing in children under 6 years of age American Thoracic Society annual convention San Diego, CA May 12, 2009
    unknown ITHS Career Development Seminar- Career Development (K Award) Seminar unknown Jan. 29, 2009

Overview

Board Certification(s)

Pediatric Pulmonology

Medical/Professional School

Harvard Medical School, Boston
University of Washington, Seattle

Clinical Interests

Diagnosis and management of all pediatric lung conditions

Research Description

Multicenter observational studies and investigator-initiated clinical trials in cystic fibrosis emphasizing early CF lung disease. Multicenter observational studies in primary ciliary dyskinesia. Development of outcome measures for clinical trials, including home spirometry, home cough monitoring, infant and preschool lung function tests. Global health, including mobile health tools for diagnosis of respiratory distress and pneumonia in low resource settings

Research Focus Area

Translational research, observational studies, investigator-initiated interventional studies