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Changes in the characteristics of approved New Drug Applications for antihypertensives

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dc.contributor.advisor Ernst R. Berndt. en_US
dc.contributor.author MacNeil, John Simon Howe en_US
dc.contributor.other Massachusetts Institute of Technology. Technology and Policy Program. en_US
dc.date.accessioned 2008-02-27T22:15:52Z
dc.date.available 2008-02-27T22:15:52Z
dc.date.copyright 2007 en_US
dc.date.issued 2007 en_US
dc.identifier.uri http://hdl.handle.net/1721.1/40373
dc.description Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, Technology and Policy Program, 2007. en_US
dc.description Includes bibliographical references (p. 83-86). en_US
dc.description.abstract In this thesis, the control of hypertension provides the backdrop for my effort to investigate how clinical trial design has evolved for antihypertensive drug submissions reviewed and approved by the Food and Drug Administration between 1988 and 2001. To do this, I have constructed and undertaken a preliminary analysis of a number of quantitative surrogate measures of complexity and scale, such as trial design, numbers of patients, treatment lengths, active drug comparators, number of indications pursued, number of indications approved, and approval times. In addition, I review how practice guidelines for the treatment of hypertension have changed with advancing clinical and biological knowledge. I attempt to investigate whether a link exists between the changing characteristics of clinical trials for antihypertensive therapies and the evolving guidelines for treating hypertension, promulgated by the Joint National Committee Report on the Detection, Evaluation, and Treatment of High Blood Pressure, (JNC), a committee assembled by the National Heart, Lung, and Blood Institute. en_US
dc.description.abstract (cont.) Although the number of New Drug Applications (NDAs) examined in the antihypertensive class is too small to permit rigorous statistical analyses, I am nonetheless able to observe a number of apparent trends within the set of NDA submissions for antihypertensives approved by the FDA. Specific trends I observe in support of increasing trial complexity include: 1) trial sizes increase over time as measured by patient enrollments per trial (p-value = 0.003); 2) clinical trial designs over time have included greater numbers of arms per trial (p-value = 0.022); and 3) the number of drug-drug interaction studies in antihypertensive NDAs has increased with time (p-value = 0.027). These trends offer preliminary support for the hypothesis that clinical trials associated with NDA applications for antihypertensives have become more complex over the last two decades. The mechanisms responsible for the observed increase in complexity are less clear. Based on available information, I cannot determine if FDA guidance documents or informal correspondence were responsible for making antihypertensive clinical trials more complicated, or whether pharmaceutical companies introduced greater complexity into the trial design for commercial reasons. en_US
dc.description.abstract (cont.) Furthermore, while I observe that FDA guidelines did not precisely track changes in JNC guidelines for treating hypertension, it is not clear whether the discrepancies are meaningful. Future research might attempt to identify more precisely the causes of increasing clinical trial complexity, and attempt to relate trial complexity to the cost of drug development more generally. en_US
dc.description.statementofresponsibility by John Simon Howe MacNeil. en_US
dc.format.extent 86 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri http://dspace.mit.edu/handle/1721.1/7582
dc.subject Technology and Policy Program. en_US
dc.title Changes in the characteristics of approved New Drug Applications for antihypertensives en_US
dc.type Thesis en_US
dc.description.degree S.M. en_US
dc.contributor.department Massachusetts Institute of Technology. Technology and Policy Program. en_US
dc.identifier.oclc 190864724 en_US


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