Proof of Concept: A PhRMA Position Paper With Recommendations for Best Practice

Cartwright, Mark E.; Cohen, Steven E.; Fleishaker, Joseph C.; Madani, Sedigheh; McLeod, James F.; Musser, Bret J.; Williams, Stephen

doi:10.1038/clpt.2009.286

Cited by 52 publications

(39 citation statements)

References 13 publications

(14 reference statements)

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“…The members of the Pharmaceutical Research and Manufacturers of America Proof of Concept Working Group recently recommended a more complex POC definition: 32 POC is the earliest point in the drug development process at which the weight of evidence suggests that it is “reasonably likely” that the key attributes for success are present and the key causes of failure are absent. To obey this definition, it is necessary to combine information about the drug from several sources, not only from a single efficacy study, and a pharmacometric analysis is well suited for including data from several studies and to combine models for both efficacy and safety into a single quantitative POC metric.…”

Section: Discussionmentioning

confidence: 99%

Comparisons of Analysis Methods for Proof‐of‐Concept Trials

Vong

Bergstrand

et al. 2013

CPT Pharmacom & Syst Pharma

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Drug development struggles with high costs and time consuming processes. Hence, a need for new strategies has been accentuated by many stakeholders in drug development. This study proposes the use of pharmacometric models to rationalize drug development. Two simulated examples, within the therapeutic areas of acute stroke and type 2 diabetes, are utilized to compare a pharmacometric model–based analysis to a t-test with respect to study power of proof-of-concept (POC) trials. In all investigated examples and scenarios, the conventional statistical analysis resulted in several fold larger study sizes to achieve 80% power. For a scenario with a parallel design of one placebo group and one active dose arm, the difference between the conventional and pharmacometric approach was 4.3- and 8.4-fold, for the stroke and diabetes example, respectively. Although the model-based power depend on the model assumptions, in these scenarios, the pharmacometric model–based approach was demonstrated to permit drastic streamlining of POC trials.

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Section: Discussionmentioning

confidence: 99%

Comparisons of Analysis Methods for Proof‐of‐Concept Trials

Vong

Bergstrand

et al. 2013

CPT Pharmacom & Syst Pharma

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“…However, much of what is presented here might apply to, or be adapted to apply to, these types of pilot or feasibility studies or similar types of trial, such as “proof of concept” or phase II trials done in the development of drugs [16, 17]. Proof of concept or phase II trials are small RCTs the main objective of which are to inform the sponsor whether or not to continue the development of a drug with larger trials.…”

Section: Scope Of This Papermentioning

confidence: 99%

CONSORT 2010 statement: extension to randomised pilot and feasibility trials

Eldridge

Chan

Campbell

et al. 2016

Pilot Feasibility Stud

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1,227

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The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply.The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist.The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number.This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials.Editor’s note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites.Electronic supplementary materialThe online version of this article (doi:10.1186/s40814-016-0105-8) contains supplementary material, which is available to authorized users.

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“…A central feature of the L2POC strategy is to pull risk forward and discharge it earlier, harvest the savings attributable to early attrition and re-deploy resources to more viable projects. For assets with favourable Phase I or POM data, clinical POC has emerged as an important development milestone owing to the crucial role of Phase II p(TS) in R&D productivity, as described by Paul et al 2 and Cartwright et al 14 . Simply put, improved Phase II p(TS) offers the greatest potential to increase the R&D productivity of any variable describing the drug development process.…”

Section: O U T Lo O Kmentioning

confidence: 97%

A decade of innovation in pharmaceutical R&D: the Chorus model

Owens

Raddad

Miller

et al. 2014

Nat Rev Drug Discov

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Chorus is a small, operationally independent clinical development organization within Eli Lilly and Company that specializes in drug development from candidate selection to clinical proof of concept. The mission of Chorus is to achieve proof of concept rapidly and at a low cost while positioning successful projects for 'pharma-quality' late-stage development. Chorus uses a small internal staff of experienced drug developers and a network of external vendors to design and implement chemistry, manufacturing and control processes, preclinical toxicology and biology, and Phase I/II clinical trials. In the decade since it was established, Chorus has demonstrated substantial productivity improvements in both time and cost compared to traditional pharmaceutical research and development. Here, we describe its development philosophy, organizational structure, operational model and results to date.

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Proof of Concept: A PhRMA Position Paper With Recommendations for Best Practice

Cited by 52 publications

References 13 publications

Comparisons of Analysis Methods for Proof‐of‐Concept Trials

Comparisons of Analysis Methods for Proof‐of‐Concept Trials

CONSORT 2010 statement: extension to randomised pilot and feasibility trials

A decade of innovation in pharmaceutical R&D: the Chorus model

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