The Value, Qualification, and Regulatory Use of Surrogate End Points in Drug Development

Lathia, CD; Amakye, Dereck D.; Dai, Wen; Girman, Cynthia J.; Madani, Sedigheh; Mayne, James T.; MacCarthy, Philip; Pertel, Peter; Seman, Leo; Stoch, Aubrey; Tarantino, Paul; Webster, CJ; Williams, S. W. D.; Ja, Wagner

doi:10.1038/clpt.2009.69

Cited by 61 publications

(53 citation statements)

References 45 publications

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“…44 44 These estimates support informal arguments made by the cancer research community; see, for example, Korn and Stanski (2005), US Institute of Medicine (2008), Lathia et al (2009), and American Society for Clinical Oncology (2011). In the case of cardiovascular disease, the set of surrogate endpoints accepted by the US FDA were initially identified by the Framingham Heart Study, a large-scale, multi-decade, federally-funded observational study which identified factors such as high blood pressure as risk factors.…”

Section: Discussionsupporting

confidence: 57%

Do Fixed Patent Terms Distort Innovation?: Evidence from Cancer Clinical Trials

Budish

Roin²,

Williams

2013

SSRN Journal

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Section: Discussionsupporting

confidence: 57%

Do Fixed Patent Terms Distort Innovation?: Evidence from Cancer Clinical Trials

Budish

Roin²,

Williams

2013

SSRN Journal

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“…Research reported in this publication was supported by the National Institute on Aging and the NIH Common Fund, 52 See, for example, the discussion in Cutler and Kadiyala (2003). 53 This type of argument has also been made informally by the cancer research community; see, for example, Korn and Stanski (2005), US Institute of Medicine (2008), Lathia et al (2009), and American Society for Clinical Oncology (2011). Collins (2012) provides an example of a technology -a chip that mimics how humans respond to a drug -that could serve the same role as a surrogate endpoint, by identifying promising candidate drugs more quickly.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…Subsequent clinical trials helped to validate these prognostic factors, which led the FDA to accept them as surrogate endpoints in cardiovascular trials (Meyskens et al 2011). Researchers have argued that without these surrogate endpoints, it is unclear whether drugs such as betablockers, ACE-inhibitors, and statins would have reached the market as treatments for heart disease (Lathia et al 2009;Meyskens et al 2011). Note that public subsidies -such as federal support for the Framingham study -were likely important in this context, because any individual firm's investment in discovering and validating surrogate endpoints would generate benefits that largely spill over to other firms.…”

Section: Budish Et Al Page 31mentioning

confidence: 99%

Do firms underinvest in long-term research? Evidence from cancer clinical trials

Budish¹,

Roin²,

Williams³

2013

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We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials -and hence, project durations -are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (nonmortality) clinicaltrial endpoints, targeted R&D subsidies, and patent design.Over the last five years, eight new drugs have been approved to treat lung cancer, the leading cause of US cancer deaths. 1 All eight drugs targeted patients with the most advanced form of lung cancer, and were approved on the basis of evidence that the drugs generated incremental improvements in survival. A well-known example is Genentech's drug Avastin, which was estimated to extend the life of late-stage lung cancer patients from 10.3 months to 12.3 months. 2 In contrast, no drug has ever been approved to prevent lung cancer, and only six drugs have ever been approved to prevent any type of cancer. While this pattern could solely reflect market demand or scientific challenges, in this paper we investigate an alternative hypothesis: private firms may invest more in late-stage cancer drugs -and "too little" in early-stage cancer and cancer prevention drugs -because late-stage cancer drugs can be brought to market comparatively quickly, whereas drugs to treat early-stage cancer Correspondence to: Heidi Williams. 1 See the lists of US Food and Drug Administration (FDA) approved hematology/oncology drugs by year: http://www.fda.gov/drugs/ informationondrugs/approveddrugs/ucm279174.htm. 2 Specifically, Avastin was approved for "unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC [non-small cell lung cancer]" patients and the clinical trial effectiveness estimate is posted on the Genentech website: http://www.gene.com/ media/product-information/avastin-lung. As noted on the website, this is the first drug to extend median survival time for this patient population beyond one year. HHS Public Access Author Manuscript Author Manuscript Author ManuscriptAuthor Manuscript and to prevent cancer require a much longer time to bring to market. More broadly stated, we investigate whether private firms differentially underinvest in long-term research, by which we mean technologies with long time lags between the initial spark of an idea and the availability of a commercially viable product. We document evidence that such underinvestment is quantitatively significant in an important context -treatments for cancer -and analyze potential policy responses.The idea that companies may be excessively focused on behaviors with short-run payoffs is an old one. A...

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“…La valeur du biomarqueur comme outil décisionnel doit par ailleurs être périodiquement réévaluée à la lumière de tous les travaux disponibles comme l'a bien montré l'historique dans d'autres domaines thérapeutiques (densité minérale osseuse pour l'ostéoporose, extra systoles ventriculaires et prévention de l'infarctus du myocarde, etc.). [2] 3. Quels biomarqueurs pour la maladie d'Alzheimer…”

Section: Disease-modifiers : Cours éVolutif Et Effet Physiopathologiqueunclassified

Biomarqueurs aux phases précoces de développement dans la maladie d’Alzheimer

et al. 2010

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Texte reçu le 4 mars 2010 ; accepté le 25 mai 2010 Mots clés :Alzheimer ; développement clinique ; biomarqueur ; imagerie Résumé -Le développement clinique de médicaments disease-modifiers dans la maladie d'Alzheimer se heurte à des difficultés méthodologiques dont témoignent plusieurs échecs récents de médicaments en phase III. Compte-tenu des enjeux financiers inhérents au passage en phase III et du risque d'investir en pure perte de l'énergie pour l'évaluation d'un mauvais candidat-médicament, la question cruciale reste la décision de go/no go entre la phase II et la phase III dont l'objectif est certes de sélectionner une molécule susceptible d'être efficace en phase III mais plus encore d'écarter d'un développement ultérieur les candidats aux effets insuffisants. Aucun consensus n'existe aujourd'hui sur la meilleure conception possible des études de phase II pour tenter d'éclairer au mieux la décision de go/nogo. Les difficultés de choix de la meilleure conception d'étude concernent tout aussi bien la population-cible, les critères de jugement en particulier le recours à des biomarqueurs, le plan expérimental ou la durée des études. L'objet de la Table Ronde (TR) a été de rassembler les points de vue d'experts français issus du monde académique, industriel ou réglementaire afin d'arriver à une proposition consensuelle sur la meilleure conception possible que devraient utiliser les études de phase II dans la maladie d'Alzheimer. Maladie d'Alzheimer : phase prodromale et démenceLes membres de la TR, en complément des résultats de celle de l'an dernier, ont réaffirmé la nécessité de distinguer la maladie d'Alzheimer dans son ensemble et la démence qui ne constitue qu'une étape évolutive de la maladie. Les membres de la TR ont bien repris à leur compte la notion de phase prodromale ou pré-démentielle de la maladie qui devrait être la cible des mé-dicaments aujourd'hui en cours d'évaluation bien que l'observation des protocoles d'études déclarés sur www.clinical-trial.gov ont encore souvent des critères d'inclusion de maladie d'AlzheiPour la liste des participants, voir en fin d'article. mer au stade de la démence, même si celle-ci est au stade léger à modéré. La discussion a évidemment alors pris en compte la notion de population sélectionnée qui peut conduire les autorités réglementaires à restreindre l'indication et le remboursement à ces seules populations-cibles. Les membres de la TR ont toutefois jugé qu'il était préférable d'avoir un médicament efficace sur une population restreinte qu'aucun médicament efficace et enregistré. Disease-modifiers : cours évolutif et effet physiopathologiqueLes membres de la TR ont discuté de la notion même de disease-modifiers considérant qu'un tel candidat-médicament doit Article publié par EDP Sciences

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The Value, Qualification, and Regulatory Use of Surrogate End Points in Drug Development

Cited by 61 publications

References 45 publications

Do Fixed Patent Terms Distort Innovation?: Evidence from Cancer Clinical Trials

Do Fixed Patent Terms Distort Innovation?: Evidence from Cancer Clinical Trials

Do firms underinvest in long-term research? Evidence from cancer clinical trials

Biomarqueurs aux phases précoces de développement dans la maladie d’Alzheimer

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