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How that chemo drug your taking found its way into your body & often saved lives

HeartofSoul's picture
HeartofSoul
Posts: 732
Joined: Dec 2009

If you hear someone say there is a treatment or drug for cancer that sounds too good to be true, well you know the rest. My first question to an "Alterantive" treatment in a country outside the US is does that country have a process for approval to market that is as rigorous and proven as the FDA? In fact, we all know of many so called "cures", easy and "very safe" treatments and that can prevent and cure your cancer right? Below is insight to how the (cancer) drugs, medical hardware and procedures reach us.

The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective

Drug Review Steps
1. Preclinical (animal) testing.
2. An investigational new drug application (IND) outlines what the sponsor of a new drug proposes for human testing in clinical trials.
3. Phase 1 studies (typically involve 20 to 80 people).
4. Phase 2 studies (typically involve a few dozen to about 300 people).
5. Phase 3 studies (typically involve several hundred to about 3,000 people).
6. The pre-NDA period, just before a new drug application (NDA) is submitted. A common time for the FDA and drug sponsors to meet.
7. Submission of an NDA is the formal step asking the FDA to consider a drug for marketing approval.
8. After an NDA is received, the FDA has 60 days to decide whether to file it so it can be reviewed.
9. If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor's research on the drug's safety and effectiveness.
10. The FDA reviews information that goes on a drug's professional labeling (information on how to use the drug).
11. The FDA inspects the facilities where the drug will be manufactured as part of the approval process.
12. FDA reviewers will approve the application or issue a complete response letter.

The path a drug travels from a lab to your medicine cabinet is usually long, and every drug takes a unique route. Often, a drug is developed to treat a specific disease. An important use of a drug may also be discovered by accident

Most drugs that undergo preclinical (animal) testing never even make it to human testing and review by the FDA. The drugs that do must undergo the agency's rigorous evaluation process, which scrutinizes everything about the drug--from the design of clinical trials to the severity of side effects to the conditions under which the drug is manufactured.

Stages of Drug Development and Review
Investigational New Drug Application (IND)--The pharmaceutical industry sometimes seeks advice from the FDA prior to submission of an IND. Sponsors--companies, research institutions, and other organizations that take responsibility for developing a drug--must show the FDA results of preclinical testing they've done in laboratory animals and what they propose to do for human testing. At this stage, the FDA decides whether it is reasonably safe for the company to move forward with testing the drug in humans.

Clinical Trials--Drug studies in humans can begin only after an IND is reviewed by the FDA and a local institutional review board (IRB). The board is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical research.

IRBs approve the clinical trial protocols, which describe the type of people who may participate in the clinical trial, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, the study's objectives, and other details. IRBs make sure the study is acceptable, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm.

Phase 1 studies are usually conducted in healthy volunteers. The goal here is to determine what the drug's most frequent side effects are and, often, how the drug is metabolized and excreted. The number of subjects typically ranges from 20 to 80.

Phase 2 studies begin if Phase 1 studies don't reveal unacceptable toxicity. While the emphasis in Phase 1 is on safety, the emphasis in Phase 2 is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition. For controlled trials, patients receiving the drug are compared with similar patients receiving a different treatment--usually an inactive substance (placebo), or a different drug. Safety continues to be evaluated, and short-term side effects are studied. Typically, the number of subjects in Phase 2 studies ranges from a few dozen to about 300.

At the end of Phase 2, the FDA and sponsors try to come to an agreement on how the large-scale studies in Phase 3 should be done. How often the FDA meets with a sponsor varies, but this is one of two most common meeting points prior to submission of a new drug application. The other most common time is pre-NDA--right before a new drug application is submitted.

Phase 3 studies begin if evidence of effectiveness is shown in Phase 2. These studies gather more information about safety and effectiveness, studying different populations and different dosages and using the drug in combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000 people.

Postmarket requirement and commitment studies are studies required of or agreed to by a sponsor that are conducted after the FDA has approved a product for marketing. The FDA uses postmarket requirement and commitment studies to gather additional information about a product's safety, efficacy, or optimal use.

New Drug Application (NDA)--This is the formal step a drug sponsor takes to ask that the FDA consider approving a new drug for marketing in the United States. An NDA includes all animal and human data and analyses of the data, as well as information about how the drug behaves in the body and how it is manufactured.

When an NDA comes in, the FDA has 60 days to decide whether to file it so that it can be reviewed. The FDA can refuse to file an application that is incomplete. For example, some required studies may be missing. In accordance with the Prescription Drug User Fee Act (PDUFA), the FDA's Center for Drug Evaluation and Research (CDER) expects to review and act on at least 90 percent of NDAs for standard drugs no later than 10 months after the applications are received. The review goal is six months for priority drugs.

"It's the clinical trials that take so long--usually several years," says Sandra Kweder, M.D., deputy director of the Office of New Drugs in the CDER. "The emphasis on speed for FDA mostly relates to review time and timelines of being able to meet with sponsors during a drug's development," she says.

Reviewing Applications
Though FDA reviewers are involved with a drug's development throughout the IND stage, the official review time is the length of time it takes to review a new drug application and issue an action letter, an official statement informing a drug sponsor of the agency's decision.

Once a new drug application is filed, an FDA review team--medical doctors, chemists, statisticians, microbiologists, pharmacologists, and other experts--evaluates whether the studies the sponsor submitted show that the drug is safe and effective for its proposed use. No drug is absolutely safe; all drugs have side effects. "Safe" in this sense means that the benefits of the drug appear to outweigh the risks.

The review team analyzes study results and looks for possible issues with the application, such as weaknesses of the study design or analyses. Reviewers determine whether they agree with the sponsor's results and conclusions, or whether they need any additional information to make a decision.

Each reviewer prepares a written evaluation containing conclusions and recommendations about the application. These evaluations are then considered by team leaders, division directors, and office directors, depending on the type of application.

Reviewers receive training that fosters consistency in drug reviews, and good review practices remain a high priority for the agency.
Sometimes, the FDA calls on advisory committees, who provide FDA with independent opinions and recommendations from outside experts on applications to market new drugs, and on FDA policies. Whether an advisory committee is needed depends on many things.

"Some considerations would be if it's a drug that has significant questions, if it's the first in its class, or the first for a given indication," says Mark Goldberger, M.D., a former director of one of CDER's drug review offices. "Generally, FDA takes the advice of advisory committees, but not always," he says. "Their role is just that--to advise."

Accelerated Approval
Traditional approval requires that clinical benefit be shown before approval can be granted. Accelerated approval is given to some new drugs for serious and life-threatening illnesses that lack satisfactory treatments. This allows an NDA to be approved before measures of effectiveness that would usually be required for approval are available.
Instead, less traditional measures called surrogate endpoints are used to evaluate effectiveness. These are laboratory findings or signs that may not be a direct measurement of how a patient feels, functions, or survives, but are considered likely to predict benefit.

Because premarket review can't catch all potential problems with a drug, the FDA continues to track approved drugs for adverse events through a postmarketing surveillance program.

Bumps in the Road
If the FDA decides that the benefits of a drug outweigh the risks, the drug will receive approval and can be marketed in the United States. But if there are problems with an NDA or if more information is necessary to make that determination, the FDA may issue a complete response letter.

Common problems include unexpected safety issues that crop up or failure to demonstrate a drug's effectiveness. A sponsor may need to conduct additional studies--perhaps studies of more people, different types of people, or for a longer period of time.

Common problems include unexpected safety issues that crop up or failure to demonstrate a drug's effectiveness. A sponsor may need to conduct additional studies--perhaps studies of more people, different types of people, or for a longer period of time.

Manufacturing issues are also among the reasons that approval may be delayed or denied. Drugs must be manufactured in accordance with standards called good manufacturing practices, and the FDA inspects manufacturing facilities before a drug can be approved. If a facility isn't ready for inspection, approval can be delayed. Any manufacturing deficiencies found would need to be corrected before approval.

"Sometimes a company may make a certain amount of a drug for clinical trials. Then when they go to scale up, they may lose a supplier or end up with quality control issues that result in a product of different chemistry," says the FDA's Kweder. "Sponsors have to show us that the product that's going to be marketed is the same product that they tested."
John Jenkins, M.D., director of CDER's Office of New Drugs, says, "It's often a combination of problems that prevent approval." Close communication with the FDA early on in a drug's development reduces the chance that an application will have to go through more than one cycle of review, he says. "But it's no guarantee."

The FDA outlines the justification for its decision in a complete response letter to the drug sponsor and CDER gives the sponsor a chance to meet with agency officials to discuss the deficiencies. At that point, the sponsor can choose to ask for a hearing, or correct any deficiencies and submit new information, or they can withdraw the application.

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