Ebook Evaluating clinical research (2/E): Part 2
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Ebook Evaluating clinical research (2/E): Part 2
Ebook Evaluating clinical research (2/E): Part 2
Chapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2Chapter 13. In this chapter, we expand the discussion to include the utility of these markers, especially in terms of their treatment-induced effects on patient care and whether findings from the first members of a drug class should be extrapolated to subsequent “me-too” drugs of the same class.Do s Ebook Evaluating clinical research (2/E): Part 2urrogate markers predict benefit in individuals?It has been generally assumed that only patients with hypercholesterolemia or hypertension benefit froEbook Evaluating clinical research (2/E): Part 2
m lipid'-lowering or antihypertensive treatment. Recent trial reports, however, have raised questions about these assumptions.I he 1 leart Protection Chapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2normal and abnormal serum lipids, as well as those with and without a history of vascular disease. Convincing subgroup analyses demonstrated that subjects with normal lipids and no vascular history (i.e., those with no indication for statin treatment) benefited the same as those in other subgroups, Ebook Evaluating clinical research (2/E): Part 2in terms of relative event reduction. The authors raised the logical question — Is elevated total or LDL cholesterol in serum a reliable indicator forEbook Evaluating clinical research (2/E): Part 2
initiation of lipid-lowering (statin) treatment? Should treatment guidelines and treatment decisions be based only on these measures? Clearly, drugs Chapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2I in project was designed to determine whether increases in IIDL- cholesterol would reduce recurrent coronary events in a long-term, placebo-controlled trial involving more than 2,500 coronary patients. Using multivariate analysis, the investigators determined how much of the observed9596Chapter 19 Ebook Evaluating clinical research (2/E): Part 2- Do changes in biologic markers predict clinical benefit?reduction in coronary' events could be explained by rhe presumed beneficial mechanism of actEbook Evaluating clinical research (2/E): Part 2
ion -- the increase in HDL- cholesterol.The result was surprising — only 23%! Thus, more than three quarters of rhe observed benefit was attributable Chapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2 be rhe major contributor to clinical benefit.Similar findings seem to apply to the use of antihypertensive treatment. In the PROGRESS project,3 normotensive patients with a history of cerebrovascular events benefited as much as their hypertensive counterparts. This raises the question... who should Ebook Evaluating clinical research (2/E): Part 2 start on antihypertensive therapy and when?Does blood pressure lowering predict clinical benefit?Blood pressure lowering is one of rhe most well-knowEbook Evaluating clinical research (2/E): Part 2
n surrogate markers. It is well established that hypertension increases the risks of stroke, acute myocardial infarction and heart failure. Avery largChapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2But can we conclude that the entire benefit of treatment is mediated through blood pressure lowering? Or do antihypertensive agents have meaningful actions that arc unrelated to blood pressure lowering? (Towing evidence indicates that the latter is the case, so the choice of antihypertensive may be Ebook Evaluating clinical research (2/E): Part 2important.According to many studies, most of rhe benefit in reducing stroke occurrence is attributable directly to blood pressure lowering. Thus, forEbook Evaluating clinical research (2/E): Part 2
stroke prevention, drug selection may be less of an issue. For other vascular events, drug choice is more critical. The ALLHAT study6 reported that doChapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2ups. The calcium channel blocker amlodipine (Norvasc) increased heart failure risk by 40%, while again yielding equivalent blood pressure reductions in patients receiving amlodipine or a diuretic.” These observations confirm that drugs have multiple mechanisms of action and that reliance on just one Ebook Evaluating clinical research (2/E): Part 2 as a surrogate marker is misguided. These non-blood pressure-mediated actions, which are not yet completely understood, can add to or detract from thEbook Evaluating clinical research (2/E): Part 2
e benefit of blood pressure lowering per se.Chapter 19 - Do changes in biologic markers predict clinical benefit?97Should changes in a surrogate markeChapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2e of the first drug of a particular class. Clinicians and regulatory agencies prefer to sec trial evidence of event reductions. Wien simvastatin (Zocor) was shown to reduce total and LDL-cholesterol, the 1*1>A approved the drug, but asked for outcome trials. When the first large simvastatin trial, 4 Ebook Evaluating clinical research (2/E): Part 2S,6 showed a convincing reduction in all-cause mortality in coronary patients, use of the drug increased markedly. It is appropriate that the clinicalEbook Evaluating clinical research (2/E): Part 2
criteria for accepting the first drug of a class are themost stringent. Should later drugs of the same class, the typical “me-too” drugs, be held to Chapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2o,” respectively.Cerivastatin (Baycol) was introduced as a potent lipid-lowering agent, and promoted as “another statin.” Many were led to believe that it was interchangeable with the other approved statins, which had very positive event and safety data. By lowering the cost of the drug compared to Ebook Evaluating clinical research (2/E): Part 2the other brandname statins, the manufacturer of cerivastatin succeeded in gaining modest market share. I lowever, cerivastarin had harmful non-cholesEbook Evaluating clinical research (2/E): Part 2
terol-lowering98Chapter 19 - Do changes in biologic markers predict clinical benefit?actions that were never properly reported.4 It caused a higher riChapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2is story is just another reminder that drugs have multiple actions and that similarity in one mechanism of action does not mean interchangeability. All members of a drug class ought to be subjected to strict regulatory oversight prior to approval. Evidence of overall health benefits and safety canno Ebook Evaluating clinical research (2/E): Part 2t be determined with certainty by investigating surrogate markers.Key Points--- Biologic markers are imperfect measures in predicting drug benefit orEbook Evaluating clinical research (2/E): Part 2
harm. — Surrogate efficacy should not form the basis for determining class effects.“A substitute shines brightly as a King until a King be by ”(W. ShaChapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2uestions. Most scientists share this goal, recognizing that the outcomes of research projects arc unpredictable in terms of direction and magnitude. Unfortunately, uncertainty about the outcome of a trial may create conflicts for those with vested or self-serving interests, whether they be financial Ebook Evaluating clinical research (2/E): Part 2 or scientific. Authors must take full responsibility for their published articles, even if the trials arc designed and conducted by a for-profit sponEbook Evaluating clinical research (2/E): Part 2
sor.One key factor contributing to this potential bias relates to the authors of scientific articles, who typically exercise total control over what iChapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2 study findings has certain advantages. It increases the likelihood of getting the article published in a reptp table journal, leads to peer recognition, invitations to conferences and academicpromotions, and brings more funding opportunities from industry sponsors.These potential conflicts of inter Ebook Evaluating clinical research (2/E): Part 2est are well recognized by medical journal editors, who have taken actions to deal with them. Simple disclosure is easy, but this does not preclude faEbook Evaluating clinical research (2/E): Part 2
vorable spinning of trial results.What do journals do?In 1984, the New England Journal of Medicine was the first medical journal to require authors ofChapter 19Do changes in biologic markers predict clinical benefit?The limitations of biologic or surrogate markers in drug evaluation are covered in C Ebook Evaluating clinical research (2/E): Part 2th this policy was not very strict. Even the NEJMadmitted failure to follow its own guidance for eighteen review articles.1rhe rules are getting even more stringent. They now apply to all coauthors and have been broadened to include journal reviewers. Disclosure of potential conflicts is now part of Ebook Evaluating clinical research (2/E): Part 2 funding decisions at the National Institutes of Health and also contributes to decisions about who can serve on FDA Advisory99Gọi ngay
Chat zalo
Facebook