Draft:Original research/Proof of concept

"Evidence that demonstrates that a business model or idea is feasible" is called proof of concept.

An idea is also a concept.

Theory
Def. evidence that demonstrates that a concept is possible is called proof of concept.

Def. a "short and/or incomplete realization of a certain method or idea to demonstrate its feasibility" is called a proof of concept.

Structures
The proof-of-concept structure consists of
 * 1) background,
 * 2) procedures,
 * 3) findings, and
 * 4) interpretation.

Phase I
"Proof of Concept PoC refers to early clinical drug development, conventionally divided into Phase I and Phase IIa."

"Phase I is typically conducted in 10-20 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 antihypertensive 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 (so-called ADME studies)."

Phase II
"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 antihypertensive 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."

"[A] proof-of-concept prototype is used in the initial stages of design."

Clinical trials
"However, definitive proof of concept would require prospective clinical trial evidence that demonstrates that optimization of dyslipidemia would result in a reduction in risk from the complications of atherosclerosis."

"[F]our volunteers infected with HIV [are] on highly-active antiretroviral therapy (HAART) [which is intensified] with subcutaneous enfuvirtide ... [and supplemented by] oral valproic acid ... [L]atent infection [is quantified] before and after augmented treatment by limiting-dilution culture of resting CD4+ T cells after ex-vivo activation. The frequency of resting cell infection was stable before addition of enfuvirtide and valproic acid, but declined thereafter."

Def. a "comparison test of a medication or other medical treatment (such as a medical device), [usually a comparison against] versus a placebo (inactive look-a-like), other medications or devices, or the standard medical treatment for a patient's condition" is called a clinical trial.

Proof of market
"The "any part" clause, however, applies to charges of monopolization as well as to attempts to monopolize, and it is beyond doubt that the former requires proof of market power in a relevant market."

Proof of mechanism
"Proof of Mechanism or PoM relates to the earliest stages of drug development, often pre-clinical (i.e., before the drug is given to humans, or before given to research animals). It could be based on showing that the drug interacts with the intended molecular receptor or enzyme, and/or affects cell biochemistry in the desired manner and direction. A decision is made at this point as to whether to progress the drug into later development, or if it should be dropped."

"Incorporating tracking studies into clinical trials of cell-based therapy at the earliest stage can provide proof of mechanism of the therapy and permit evaluation of the many contributory variables, even on a patient-by-patient basis."

"[B]iochemical markers [may be used] for early proof of mechanism"

"One early “proof of mechanism” study of farglitazar, a non-TZD PPARγ agonist, assessed 24-h insulin and glucose profiles in a double-blind, randomized, placebo-controlled study in patients with type 2 diabetes."

Proof of principle
"Proof of Principle" or PoP relates to early clinical development and typically refers to an evaluation of the effect of a new treatment on disease biomarkers, but not the clinical endpoints of the condition.

For specific drug development, "Proof of Principle studies are an early stage of clinical drug development when a compound has shown potential in animal models and early safety testing. This step of proof-of-principle (PoP) or proof-of-concept (PoC) often links between Phase-I and dose ranging Phase-II studies. These small-scale studies are designed to detect a signal that the drug is active on a pathophysiologically relevant mechanism, as well as preliminary evidence of efficacy in a clinically relevant endpoint."

"[A] simple, yet stringent, “proof of principle” study to answer the question, “Can dogs be trained to detect bladder cancer more successfully than would be expected by chance alone?” [resulted in] a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone."

Proof of process
"Although the laws since 19th century mostly require "personal service" of process, and sworn "proof of process" that the defendant has received notice of trial, in many areas the parties involved in service of process get away with perjured proof of process, claiming to have delivered the legal documents which in fact have not reached defendant (but rather been discarded "in sewer")."

"One obvious route often suggested in much literature is a proof-of-process approach; that is, to require front matter from students—notes, drafts, sources, and so on."

"Of all the methods available to generate the “scientific evidence,” the classical inoculated pack studies are recognized to provide the ultimate proof of process adequacy for a specified set of conditions."

"A proof-of-process prototype shows that the production methods and materials can successfully result in the desired product."

Proof of product
A proof of product may consist of a new delivery formulation coupled to another process (product) for delivery. Proof-of-product is achieved first by a proof-of-concept match between the experimental profile from the new delivery formulation plus new process of delivery to "the effect of the standard regimen" and finally by a match "for onset and duration of efficacy".

"[A] proof-of-product prototype clarifies a design's physical embodiment and production feasibility."

Proof of production
"A notable exception is the Climate Change Levy: [Levy Exemption Certificates] LECs are issued by the UK regulator to electricity producers both in the UK and in a number of European countries and exported to the UK, where they are purchased as proof of production of renewable energy production."

"[A] proof-of-production prototype demonstrates that the complete manufacturing process is effective."

Proof of relevance
"This has to include the proof of relevance, ie, that changes in the marker are correlated to changes in disease state or outcome, as well as criteria similar to those used in analytical method validation, as repeatability, reproducibility, and sensitivity."

"We can become deluded into thinking that approval of peers through review processes is proof of relevance and social value."

Def. "proving that the event reporter is authentically relevant to the event it has reported" is called a proof of relevance.

Proof of technology
"[T]he objective of a proof of technology is to determine the solution to some technical problem, such as how two systems might be integrated or that a certain throughput can be achieved with a given configuration."

Def.
 * 1) "[a]n original object or form which is a basis for other objects, forms, or for its models and generalizations",
 * 2) "[a]n early sample or model built to test a concept or process", or
 * 3) "[a]n instance of a category or a concept that combines its most representative attributes" is called a prototype.

Def. "[t]o test something using the conditions that it was designed to operate under, especially out in the real world instead of in a laboratory or workshop" is called "field-test", or a field test.

A "proof-of-technology prototype ... typically implements one critical scenario to exercise or stress the highest-priority requirements."

"[A] proof-of-technology test demonstrates the system can be used".

"The strongest proof of technology performance is based on consistency among multiple lines of evidence, all pointing to similar levels of risk reduction."

Hypotheses

 * 1) Proof of concept should be the minimum necessary and sufficient for the proof.