Gelb BD, Roberts AE, Tartaglia M Cardiomyopathies in Noonan syndrome and the other RASopathies. Prog Pediatr Cardiol. 2015 Jul 1;39(1):13-19. doi: 10.1016/j.ppedcard.2015.01.002.
Jhang WK, Choi JH, Lee BH, Kim GH, Yoo HW Cardiac Manifestations and Associations with Gene Mutations in Patients Diagnosed with RASopathies. Pediatr Cardiol. 2016 Dec;37(8):1539-1547. doi: 10.1007/s00246-016-1468-6. Epub 2016 Aug 23.
Kim EK, Choi EJ Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010 Apr;1802(4):396-405. doi: 10.1016/j.bbadis.2009.12.009. Epub 2010 Jan 14.
Pierpont EI, Wolford M Behavioral functioning in cardiofaciocutaneous syndrome: Risk factors and impact on parenting experience. Am J Med Genet A. 2016 Aug;170(8):1974-88. doi: 10.1002/ajmg.a.37725. Epub 2016 May 5.
Ratner N, Miller SJ A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer. 2015 May;15(5):290-301. doi: 10.1038/nrc3911. Epub 2015 Apr 16.
Schubbert S, Bollag G, Shannon K Deregulated Ras signaling in developmental disorders: new tricks for an old dog. Curr Opin Genet Dev. 2007 Feb;17(1):15-22. doi: 10.1016/j.gde.2006.12.004.
Smpokou P, Zand DJ, Rosenbaum KN, Summar ML Malignancy in Noonan syndrome and related disorders. Clin Genet. 2015 Dec;88(6):516-22. doi: 10.1111/cge.12568. Epub 2015 Mar 4.
Interventional studies are often prospective and are specifically tailored to evaluate direct impacts of treatment or preventive measures on disease.
Observational studies are often retrospective and are used to assess potential causation in exposure-outcome relationships and therefore influence preventive methods.
Expanded access is a means by which manufacturers make investigational new drugs available, under certain circumstances, to treat a patient(s) with a serious disease or condition who cannot participate in a controlled clinical trial.
Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.
Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.
