Belousoff
07.02.2006, 17:04
Всем добрый день! Вот, попалась на глаза любопытная заметка:
The investigational new drug application—who benefits?
Emil J Freireich, Nature Clinical Practice Oncology (2006) 3, 62-63
[Ссылки могут видеть только зарегистрированные и активированные пользователи]
The FDA performs an important regulatory function in protecting the US public from the marketing of drugs that are either dangerous or not effective.1 The federal law that created the Investigational New Drug (IND) process—the Federal Food, Drug and Cosmetic Act—was enacted in 1938; it required that the FDA be informed before any new treatment was administered to humans.2 Unfortunately, in 1962, following the recognition of the teratogenic effect of thalidomide in children born to women who were receiving this drug outside the US, Congress enacted a new amendment to the original Food and Drug Act of 1938—the Kefauver–Harris Drug Amendments. This changed the IND process from one of notification to one of approval. It was now required that FDA officials approve the initiation of a phase I trial, so that FDA approval was necessary before a drug could be given to a human being. Since that legislation was passed, the requirements for the IND application have progressively escalated, as has the cost of new drug development. It is now estimated that the time from conception of a new drug to its approval is in excess of 15 years, and that over two-thirds of this time is devoted to pre-IND testing.3 During this 10-year period of delay, over six million Americans will die from cancer. Of course, if the progressively escalating requirements for preclinical data for an IND provided further protection for patients, they would be justified. But, tragically, at the time of the legislation in 1962, there was no known preclinical test that could have predicted the thalidomide disaster, and, to a large extent, the preclinical data obtained during the IND process are of only limited usefulness when progressing to clinical trial.4 With modern techniques, it is possible to approach a phase I trial in an objective and quantitative manner, using pharmacological techniques and sophisticated in vitro techniques for predicting potential effectiveness and toxicities. Unfortunately, innovative developments in science are not rapidly appreciated by regulatory officials employed by the FDA.
Although it is certain that the FDA employees who review IND applications are highly competent and well trained, it is nonetheless true that each individual is in a position where, should they approve an application that subsequently causes harmful effects in humans, it would be much to the detriment of their career. By contrast, if such a treatment were highly effective, they would get no reward for having been astute enough to allow the early introduction of this drug into clinical trial. Consequently, all of the social and psychological forces acting on this person are compelling them either to deny approval or to delay approval and require additional data, which is the usual response to an IND application.
In 1988, when the AIDS epidemic gained public awareness, the FDA allowed for a 'treatment IND' program. This allowed the drug sponsor to provide the drug to patients in situations where the physician felt it was indicated, but where the patient was not eligible for a clinical trial, and a new drug application (NDA) had not yet been issued. Unfortunately, since that time the 'treatment IND' option has been eliminated and the compassionate use of drugs is rarely, if ever, permitted.
The net result currently is that no one benefits from the IND procedure. Certainly patients who could potentially benefit are denied the opportunity to receive investigational drugs if they are not eligible for entry into the clinical trial, even when the treating physician and a whole host of academic physicians support the use for the patient. Certainly the government does not benefit. A huge allocation of resources, which is supported by taxpayer dollars, is required for a process that is of questionable value. The public at large does not benefit, since investigational drugs are never made available to the public by prescription by a non-research physician, unless the NDA is issued by the FDA.
And perhaps the worst effect of the IND is on the academic process. The IND procedure smacks of 'Lysenkoism', a campaign in the former Soviet Republic against research in genetics when this conflicted with the social policy of the government.5 In the US—a country that cherishes political and particularly academic freedom—we have a situation where the academic physician scientist, who has access to the most data, has to petition the government for permission to undertake clinical research. This is clearly an infringement on academic freedom, which we should no longer tolerate.
It is important to note that the clinical investigative process within academic institutions is already regulated by the Federal Government through the Office for Protection from Research Risks.6 Every academic institution is required to have an institutional review board (IRB), which must review any proposal to conduct research in humans. Thus, the potential for exposing patients to dangerous or unethical treatments is guarded against by the IRB process within academic institutions. In addition, in an academic institution, every proposal to investigate a new drug in a phase I study has to be peer reviewed by the chairman of the department sponsoring the study, an institutional research committee, the administrative person in charge of research in the institution, and very often by the sponsor who funds the research, which is either a federal or a volunteer agency.
In summary, the IND process has many negative effects and no benefits. It seems clear that the time has come to abandon the IND process, probably by decentralizing the process and allocating the review and approval authority to academic centers where such clinical research is ongoing.7 That is a recommendation from which everyone would benefit—the patients, the academic scientist, and the government—through simplifying the process of drug development, and thereby reducing the cost of drug development and the cost of monitoring of the IND process to the taxpayers.
[Ссылки могут видеть только зарегистрированные и активированные пользователи]
Какие будут мнения?
The investigational new drug application—who benefits?
Emil J Freireich, Nature Clinical Practice Oncology (2006) 3, 62-63
[Ссылки могут видеть только зарегистрированные и активированные пользователи]
The FDA performs an important regulatory function in protecting the US public from the marketing of drugs that are either dangerous or not effective.1 The federal law that created the Investigational New Drug (IND) process—the Federal Food, Drug and Cosmetic Act—was enacted in 1938; it required that the FDA be informed before any new treatment was administered to humans.2 Unfortunately, in 1962, following the recognition of the teratogenic effect of thalidomide in children born to women who were receiving this drug outside the US, Congress enacted a new amendment to the original Food and Drug Act of 1938—the Kefauver–Harris Drug Amendments. This changed the IND process from one of notification to one of approval. It was now required that FDA officials approve the initiation of a phase I trial, so that FDA approval was necessary before a drug could be given to a human being. Since that legislation was passed, the requirements for the IND application have progressively escalated, as has the cost of new drug development. It is now estimated that the time from conception of a new drug to its approval is in excess of 15 years, and that over two-thirds of this time is devoted to pre-IND testing.3 During this 10-year period of delay, over six million Americans will die from cancer. Of course, if the progressively escalating requirements for preclinical data for an IND provided further protection for patients, they would be justified. But, tragically, at the time of the legislation in 1962, there was no known preclinical test that could have predicted the thalidomide disaster, and, to a large extent, the preclinical data obtained during the IND process are of only limited usefulness when progressing to clinical trial.4 With modern techniques, it is possible to approach a phase I trial in an objective and quantitative manner, using pharmacological techniques and sophisticated in vitro techniques for predicting potential effectiveness and toxicities. Unfortunately, innovative developments in science are not rapidly appreciated by regulatory officials employed by the FDA.
Although it is certain that the FDA employees who review IND applications are highly competent and well trained, it is nonetheless true that each individual is in a position where, should they approve an application that subsequently causes harmful effects in humans, it would be much to the detriment of their career. By contrast, if such a treatment were highly effective, they would get no reward for having been astute enough to allow the early introduction of this drug into clinical trial. Consequently, all of the social and psychological forces acting on this person are compelling them either to deny approval or to delay approval and require additional data, which is the usual response to an IND application.
In 1988, when the AIDS epidemic gained public awareness, the FDA allowed for a 'treatment IND' program. This allowed the drug sponsor to provide the drug to patients in situations where the physician felt it was indicated, but where the patient was not eligible for a clinical trial, and a new drug application (NDA) had not yet been issued. Unfortunately, since that time the 'treatment IND' option has been eliminated and the compassionate use of drugs is rarely, if ever, permitted.
The net result currently is that no one benefits from the IND procedure. Certainly patients who could potentially benefit are denied the opportunity to receive investigational drugs if they are not eligible for entry into the clinical trial, even when the treating physician and a whole host of academic physicians support the use for the patient. Certainly the government does not benefit. A huge allocation of resources, which is supported by taxpayer dollars, is required for a process that is of questionable value. The public at large does not benefit, since investigational drugs are never made available to the public by prescription by a non-research physician, unless the NDA is issued by the FDA.
And perhaps the worst effect of the IND is on the academic process. The IND procedure smacks of 'Lysenkoism', a campaign in the former Soviet Republic against research in genetics when this conflicted with the social policy of the government.5 In the US—a country that cherishes political and particularly academic freedom—we have a situation where the academic physician scientist, who has access to the most data, has to petition the government for permission to undertake clinical research. This is clearly an infringement on academic freedom, which we should no longer tolerate.
It is important to note that the clinical investigative process within academic institutions is already regulated by the Federal Government through the Office for Protection from Research Risks.6 Every academic institution is required to have an institutional review board (IRB), which must review any proposal to conduct research in humans. Thus, the potential for exposing patients to dangerous or unethical treatments is guarded against by the IRB process within academic institutions. In addition, in an academic institution, every proposal to investigate a new drug in a phase I study has to be peer reviewed by the chairman of the department sponsoring the study, an institutional research committee, the administrative person in charge of research in the institution, and very often by the sponsor who funds the research, which is either a federal or a volunteer agency.
In summary, the IND process has many negative effects and no benefits. It seems clear that the time has come to abandon the IND process, probably by decentralizing the process and allocating the review and approval authority to academic centers where such clinical research is ongoing.7 That is a recommendation from which everyone would benefit—the patients, the academic scientist, and the government—through simplifying the process of drug development, and thereby reducing the cost of drug development and the cost of monitoring of the IND process to the taxpayers.
[Ссылки могут видеть только зарегистрированные и активированные пользователи]
Какие будут мнения?