Brief Analysis of Drug Effectiveness Evaluation in the United States

In the first half of last year, the "drug consistency evaluation" carried out in China was undoubtedly a revolution in China's pharmaceutical industry. Looking back on history, drug consistency evaluation has many similarities with the American "drug Efficacy study Implementation" (DESI) that occurred in the late 1960 s.

Thalidomide events in the 1960s led to the Kefauver-Harris Act in the United States. The bill not only created a revolution in the concept of the modern pharmaceutical industry, but also has been the basic framework of drug regulations in the world for nearly 60 years, and even directly imitated by 80% of countries. The bill is known as the "Bible of modern medicine". Uniform emphasis on drug safety and effectiveness is the essence of the bill. In line with the principle of safety and effectiveness, Kefauver-Harris bill has made strict and scientific provisions on the research, development and listing of new drugs, as well as the corresponding review and approval procedures.

But what to do with drugs that went on the market from 1938 to 1962 is a vexing problem. None of these drugs have been reviewed for "effectiveness" under the 1938 Act. Kefauver bill only conceptually proposes that these 4000 drug effectiveness issues must be addressed and authorized by the FDA to implement them. However, who is specifically responsible and how to solve this problem has always been avoided.

Why avoid it?

First, opening the effectiveness evaluation may lead to a large area of drug off the shelf, which will cause confusion and disorder in treatment.

Second, at that time, FDA had a large number of human resources to deal with investigative new drug and new drug applications (IND,NDA), and could not spare manpower to participate in drug efficacy evaluation. In addition, the knowledge, experience, and ability of FDA employees themselves are not sufficient to evaluate such a large number of drugs.

Third, under state law, drug delisting is subject to a hearing. 4000 medicine, 4000 hearing, that is an impossible task.

In June 1966, James Goddard took office as FDA director (1966-1968). Goddard determined to solve the biggest problem facing FDA: to start the effectiveness evaluation of about 4000 listed drugs pre-1962 and announce the start of DESI(Drug Efficacy Study Initiative). Goddard first signed contracts with the National Academy of Sciences (NAS) and the National Academic Council (NRC), and national scientists made effectiveness reports on pre-1962 drugs according to disciplines. At the same time, drug manufacturers were required to submit evidence of the drug's effectiveness by January 14, 1967. 180 scientists from the Academy of Sciences divided into 30 research groups and began to work. They reviewed and evaluated drugs based on drug briefs provided by drugmakers; supplemental evidence of effectiveness provided by drugmakers; FDA documentation; and existing literature.

Since 1968, the FDA has gradually published the results of the evaluation in "Federal Proclamation" (Federal Register). From 1969 to 1970, the evaluation results of a large number of drugs were published, and DES was transferred to the implementation stage (Drug Efficacy Study Implementation). That is, as the Federal Register continue to publish DES reports, ineffective drugs began to withdraw from the market. The conflict broke out, and the drugmaker and the American Medical Association joined forces to challenge the FDA. In 1969, the FDA took Upjohn's Panalba (tetracycline and neomycin combination) and proposed to expel the combination antibiotic drug from the market. But met with stiff resistance from Upjohn. Upjohn believes that the FDA does not have the power to decide on drug delisting, which must be heard by Congress. The American Medical Association (AMA) sided with Upjohn, saying that "the free right of American doctors to use drugs" cannot be violated. Even Finch, the FDA's immediate boss at the time, U.S. Secretary of Health, Education and Welfare, asked the FDA to release the water Panalba. The new FDA director, Jey, will not hesitate to turn against his boss and expel Panalba from the US market. In the end, the U.S. Supreme Court rejected Upjohn's complaint and amended the CFR to give the FDA the right to withdraw the drug. In this way, the FDA completely removed the combined antibiotics that have been in clinical use for many years from the U.S. market. Shortly after the incident, Jey was forced to resign as FDA commissioner.

As of the promulgation of the Drug Price Competition and Patent Period Compensation Act in 1984, FDA, in cooperation with the National Academy of Sciences and the American Academic Council, has evaluated 3443 drugs through a combination of literature evaluation, expert evaluation and clinical trials, of which 2252 are effective, 1015 are ineffective and 167 are undetermined.

Since the Hatch-Waxman Law of 1984 formulated new rules for generic drugs, the efficacy evaluation of the United States, which began in 1966, has well solved the problem of "new regulations" managing "old drugs" and brought them into line with the 1984 regulations.

Borrowing legal action to get the right to delist drugs: win the Panalba's lawsuit and defeat Upjohn, so that judges, jurors, and FDA have the ability to independently judge the delisting of drugs without the need for a hearing. It is a decision that changes the legal history of the United States! Because of this case, it changed the system that the delisting of drugs in the United States requires a court hearing and gave the drug delisting right to the FDA.

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