Gladwin MT, Crawford JH, Patel RP The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation. Free Radic Biol Med. 2004 Mar 15;36(6):707-17. Review.
Gladwin MT, Schechter AN, Shelhamer JH, Ognibene FP The acute chest syndrome in sickle cell disease. Possible role of nitric oxide in its pathophysiology and treatment. Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1368-76. Review.
Hachiya T, Blaber AP, Saito M Near-infrared spectroscopy provides an index of blood flow and vasoconstriction in calf skeletal muscle during lower body negative pressure. Acta Physiol (Oxf). 2008 Jun;193(2):117-27. Epub 2007 Dec 19.
Lundberg JO, Weitzberg E Nitrite reduction to nitric oxide in the vasculature. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H477-8. doi: 10.1152/ajpheart.00611.2008. Epub 2008 Jun 27.
Raj A, Bertolone SJ, Mangold S, Edmonds HL Jr Assessment of cerebral tissue oxygenation in patients with sickle cell disease: effect of transfusion therapy. J Pediatr Hematol Oncol. 2004 May;26(5):279-83.
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.
