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Proof of concept (POC or PoC), also known as proof of principle, is a realization of a certain method or idea in order to demonstrate its feasibility, [1] or a demonstration in principle with the aim of verifying that some concept or theory has practical potential. A proof of concept is usually small and may or may not be complete.
These collaborative trials aim to test feasibility of business concepts and proposals to solve business problems and accelerate business innovation goals. [2]
A proof of value (PoV) is sometimes used along proof of concept, and differs by focusing more on demonstrating the potential customer use case and value, and is usually less in-depth than a proof of concept. [3]
The term has been in use since 1967. [4] [5] In a 1969 hearing of the Committee on Science and Astronautics, Subcommittee on Advanced Research and Technology, proof of concept was defined as following:
The Board defined proof of concept as a phase in development in which experimental hardware is constructed and tested to explore and demonstrate the feasibility of a new concept. [6]
One definition of the term "proof of concept" was by Bruce Carsten in the context of a "proof-of-concept prototype" in his magazine column "Carsten's Corner" (1989):
Proof-of-Concept Prototype is a term that (I believe) I coined in 1984. It was used to designate a circuit constructed along lines similar to an engineering prototype, but one in which the intent was only to demonstrate the feasibility of a new circuit and/or a fabrication technique, and was not intended to be an early version of a production design. [7]
The column also provided definitions for the related but distinct terms 'breadboard' (a term used since 1940 [8] ), 'prototype', 'engineering prototype', and 'brassboard'.
Sky Captain and the World of Tomorrow , 300 , and Sin City were all shot in front of a greenscreen with almost all backgrounds and props computer-generated. All three used proof-of-concept short films. In the case of Sin City, the short film became the prologue of the final film.[ citation needed ]
Pixar sometimes creates short animated films that use a difficult or untested technique. Their short film Geri's Game used techniques for animation of cloth and of human facial expressions later used in Toy Story 2 . Similarly, Pixar created several short films as proofs of concept for new techniques for water motion, sea anemone tentacles, and a slowly appearing whale in preparation for the production of Finding Nemo .[ citation needed ]
In engineering and technology, a rough prototype of a new idea is often constructed as a "proof of concept". For example, a working concept of an electrical device may be constructed using a breadboard. A patent application often requires a demonstration of functionality prior to being filed. Some universities have proof of concept centers to "fill the 'funding gap'" for "seed-stage investing" and "accelerate the commercialization of university innovations". Proof of concept centers provide "seed funding to novel, early stage research that most often would not be funded by any other conventional source". [9]
In the field of business development and sales, a vendor may allow a prospect customer to try a product. This use of proof of concept helps establish viability, isolate technical issues, and suggest an overall direction, as well as provide feedback for budgeting and other forms of internal decision-making processes.[ citation needed ]
In these cases, the proof of concept may mean the use of specialized sales engineers to ensure that the vendor makes a best-possible effort.
In both computer security and encryption, proof of concept refers to a demonstration that in principle shows how a system may be protected or compromised, without the necessity of building a complete working vehicle for that purpose. Winzapper was a proof of concept which possessed the bare minimum of capabilities needed to selectively remove an item from the Windows Security Log, but it was not optimized in any way.[ citation needed ]
In software development, the term 'proof of concept' often characterizes several distinct processes with different objectives and participant roles: vendor business roles may utilize a proof of concept to establish whether a system satisfies some aspect of the purpose it was designed for. Once a vendor is satisfied, a prototype is developed which is then used to seek funding or to demonstrate to prospective customers.[ citation needed ]
The US General Services Administration has a checklist for defining an Agile software proof of concept, which includes clear definitions of the problem, pre-POC input required, and output criteria (including success criteria). [10]
The key benefits of the proof of concept in software development are: [11]
A 'steel thread' is technical proof of concept that touches all of the technologies in a solution. By contrast, a 'proof of technology' aims to determine the solution to some technical problem (such as how two systems might integrate) or to demonstrate that a given configuration can achieve a certain throughput. No business users need be involved in a proof of technology.
A pilot project refers to an initial roll-out of a system into production, targeting a limited scope of the intended final solution. The scope may be limited by the number of users who can access the system, the business processes affected, the business partners involved, or other restrictions as appropriate to the domain. The purpose of a pilot project is to test, often in a production environment.
Tech demos are designed as proof of concept for the development of video games. [12] They can demonstrate graphical or gameplay capabilities crucial for particular games.
Although not suggested by natural language, and in contrast to usage in other areas, proof of principle and proof of concept are not synonymous in drug development. A third term, proof of mechanism, is closely related and is also described here. All of these terms lack rigorous definitions and exact usage varies between authors, between institutions and over time. The descriptions given below are intended to be informative and practically useful.[ citation needed ]
The underlying principle is related to the use of biomarkers as surrogate endpoints in early clinical trials. [13] In early development it is not practical to directly measure that a drug is effective in treating the desired disease, and a surrogate endpoint is used to guide whether or not it is appropriate to proceed with further testing. For example, although it cannot be determined early that a new antibiotic cures patients with pneumonia, early indicators would include that the drug is effective in killing bacteria in laboratory tests, or that it reduces temperature in infected patients—such a drug would merit further testing to determine the appropriate dose and duration of treatment. A new anti-hypertension drug could be shown to reduce blood pressure, indicating that it would be useful to conduct more extensive testing of long-term treatment in the expectation of showing reductions in stroke (cerebrovascular accident) or heart attack (myocardial infarction). Surrogate endpoints are often based on laboratory blood tests or imaging investigations like X-ray or CT scan.[ citation needed ]
Phase I is typically conducted with a small number of healthy volunteers who are given single doses or short courses of treatment (e.g., up to 2 weeks). Studies in this phase aim to show that the new drug has some of the desired clinical activity (e.g., that an experimental anti-hypertensive drug actually has some effect on reducing blood pressure), that it can be tolerated when given to humans, and to give guidance as to dose levels that are worthy of further study. Other Phase I studies aim to investigate how the new drug is absorbed, distributed, metabolised and excreted (ADME studies).
Phase IIA is typically conducted in up to 100 patients with the disease of interest. Studies in this Phase aim to show that the new drug has a useful amount of the desired clinical activity (e.g., that an experimental anti-hypertensive drug reduces blood pressure by a useful amount), that it can be tolerated when given to humans in the longer term, and to investigate which dose levels might be most suitable for eventual marketing.
A decision is made at this point as to whether to progress the drug into later development, or if it should be dropped. If the drug continues, it will progress into later stage clinical studies, termed Phase IIB and Phase III.
Phase III studies involve larger numbers of patients—commonly multicenter trials—treated at doses and durations representative of marketed use, and in randomised comparison to placebo and/or existing active drugs. They aim to show convincing, statistically significant evidence of efficacy and to give a better assessment of safety than is possible in smaller, short-term studies.
A decision is made at this point as to whether the drug is effective and safe, and if so an application is made to regulatory authorities (such as the US Food and Drug Administration FDA and the European Medicines Agency) for the drug to receive permission to be marketed for use outside of clinical trials.
Clinical trials can continue after marketing authorization has been received, for example, to better delineate safety, to determine appropriate use alongside other drugs or to investigate additional uses.
A prototype is an early sample, model, or release of a product built to test a concept or process. It is a term used in a variety of contexts, including semantics, design, electronics, and software programming. A prototype is generally used to evaluate a new design to enhance precision by system analysts and users. Prototyping serves to provide specifications for a real, working system rather than a theoretical one. In some design workflow models, creating a prototype is the step between the formalization and the evaluation of an idea.
Microbicides for sexually transmitted diseases are pharmacologic agents and chemical substances that are capable of killing or destroying certain microorganisms that commonly cause human infection.
In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials and during which important feasibility, iterative testing and drug safety data are collected, typically in laboratory animals.
In clinical trials, a surrogate endpoint is a measure of effect of a specific treatment that may correlate with a real clinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of Health (USA) defines surrogate endpoint as "a biomarker intended to substitute for a clinical endpoint".
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug. The entire process – from concept through preclinical testing in the laboratory to clinical trial development, including Phase I–III trials – to approved vaccine or drug typically takes more than a decade.
A pilot experiment, pilot study, pilot test or pilot project is a small-scale preliminary study conducted to evaluate feasibility, duration, cost, adverse events, and improve upon the study design prior to performance of a full-scale research project.
The HIV Prevention Trials Network (HPTN) is a worldwide collaborative clinical trials network that brings together investigators, ethicists, community and other partners to develop and test the safety and efficacy of interventions designed to prevent the acquisition and transmission of HIV. HPTN studies evaluate new HIV prevention interventions and strategies in populations and geographical regions that bear a disproportionate burden of infection. The HPTN is committed to the highest ethical standards for its clinical trials and recognizes the importance of community engagement in all phases of the research process.
Leronlimab is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. It is being investigated as a potential therapy in the treatment of COVID-19, triple negative breast cancer, and HIV infection. The United States Food and Drug Administration has designated PRO 140 for fast-track approval. In February 2008, the drug entered Phase 2 clinical trials and a phase 3 trial was begun in 2015. In February 2018, Cytodyn Inc reported that the primary endpoint had been achieved in the PRO 140 pivotal combination therapy trial in HIV infection. In 2020 CytoDyn submitted a fast-track biologics license application for treatment of CCR5-tropic HIV-1 Infection.
A glossary of terms used in clinical research.
Nuvelo Inc. was a biopharmaceutical company engaged in the discovery, development and commercialization of drugs for acute cardiovascular disease, cancer and other debilitating medical conditions. On January 27, 2009, the company was acquired by ARCA Biopharma, Inc. in a reverse takeover transaction.
Cytel is a multinational statistical software developer and contract research organization, headquartered in Cambridge, Massachusetts, USA. Cytel provides clinical trial design, implementation services, and statistical products primarily for the biotech and pharmaceutical development markets.
An imaging biomarker is a biologic feature, or biomarker detectable in an image. In medicine, an imaging biomarker is a feature of an image relevant to a patient's diagnosis. For example, a number of biomarkers are frequently used to determine risk of lung cancer. First, a simple lesion in the lung detected by X-ray, CT, or MRI can lead to the suspicion of a neoplasm. The lesion itself serves as a biomarker, but the minute details of the lesion serve as biomarkers as well, and can collectively be used to assess the risk of neoplasm. Some of the imaging biomarkers used in lung nodule assessment include size, spiculation, calcification, cavitation, location within the lung, rate of growth, and rate of metabolism. Each piece of information from the image represents a probability. Spiculation increases the probability of the lesion being cancer. A slow rate of growth indicates benignity. These variables can be added to the patient's history, physical exam, laboratory tests, and pathology to reach a proposed diagnosis. Imaging biomarkers can be measured using several techniques, such as CT, electroencephalography, magnetoencephalography, and MRI.
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for drug safety in a few human subjects, then expand to many study participants to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays.
The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. The faster approval relies on use of surrogate endpoints. Drug approval typically requires clinical trials with endpoints that demonstrate a clinical benefit, such as increased survival for cancer patients. Drugs with accelerated approval can initially be tested in clinical trials that use a surrogate endpoint, or something that is thought to predict clinical benefit. Surrogate endpoints typically require less time, and in the case of a cancer patient, it is much faster to measure a reduction in tumor size, for example, than overall patient survival.
Rislenemdaz is an orally active, selective NMDA receptor subunit 2B (NR2B) antagonist which is under development by Cerecor in the United States as an adjunctive therapy for treatment-resistant depression (TRD). In November 2013, phase II clinical trials were initiated, and in the same month, rislenemdaz received Fast Track Designation from the Food and Drug Administration for TRD.
An in silico clinical trial, also known as a virtual clinical trial, is an individualized computer simulation used in the development or regulatory evaluation of a medicinal product, device, or intervention. While completely simulated clinical trials are not feasible with current technology and understanding of biology, its development would be expected to have major benefits over current in vivo clinical trials, and research on it is being pursued.
Tradipitant is an experimental drug that is a neurokinin 1 antagonist. It works by blocking substance P, a small signaling molecule. Originally, this compound was owned by Eli Lilly and named LY686017. VLY-686 was purchased by Vanda Pharmaceuticals from Eli Lilly and Company in 2012. Vanda Pharmaceuticals is a U.S. pharmaceutical company that as of November 2015 only has three drugs in their product pipeline: tasimelteon, VLY-686, and iloperidone.
Setanaxib is an experimental orally bioavailable dual inhibitor of NADPH oxidase isoforms NOX4 and NOX1. Setanaxib is a member of the pyrazolopyridine dione chemical series. The compound is the only specific NOX inhibitor that has entered into clinical trials.
In an adaptive design of a clinical trial, the parameters and conduct of the trial for a candidate drug or vaccine may be changed based on an interim analysis. Adaptive design typically involves advanced statistics to interpret a clinical trial endpoint. This is in contrast to traditional single-arm clinical trials or randomized clinical trials (RCTs) that are static in their protocol and do not modify any parameters until the trial is completed. The adaptation process takes place at certain points in the trial, prescribed in the trial protocol. Importantly, this trial protocol is set before the trial begins with the adaptation schedule and processes specified. Adaptions may include modifications to: dosage, sample size, drug undergoing trial, patient selection criteria and/or "cocktail" mix. The PANDA provides not only a summary of different adaptive designs, but also comprehensive information on adaptive design planning, conduct, analysis and reporting.
proof of concept[:] Evidence that demonstrates that a business model or idea is feasible.
January 25, 26, and February 27, 1967, review of adequacy of policy planning for aeronautical research and development and of what Congress, Executive Branch of government, and private industry can do to insure that national aeronautical goals are met
December, 1, 2, 4, 8–11, 1969,