The FDA is currently under investigation by 3 separate Congressional Committees (see link FDA, then use the BACK ARROW to return here). This is the ideal time to launch a grass roots movement to try to change the entire process of the creation and approval of cutting-edge cancer treatment. If you are in sync with the position paper below, mail a copy to all of your Senators and Representatives. BUT DON'T STOP THERE. Copy friends and associates on your e-mail addressbook. Set appointments to meet with your Federal Political Reps in the Senate and House to ask them to introduce legislation. Create petitions. And contact any member of Government involved with the current investigations of the FDA.

POSITION PAPER: THE FDA AND APPROVAL  of  “Molecular Targeted” ANTI-CANCER DRUGS

      With several investigations of the FDA now underway, this is the correct moment to bring to light a major problem that is preventing the meaningful advance of a cure for cancer.  

 
     Current allegations assert that the FDA stifled internal critics whose new research suggested that certain drugs for various illnesses were not safe, and that the FDA attempted to minimize the new data because the FDA had already long-since granted approval to the drugs.

          It would be a serious mistake to conclude, however, that the FDA must be even more cautious before releasing all new drugs. What the current investigations stand to reveal is that in the cases of drugs already approved (and after considerable testing and caution), the FDA failed to respond to subsequent data that the drugs may not be safe after all --- and failed to pull the already released drugs ... for political reasons; like protecting their own jobs, and protecting the revenues of the drug manufacturers.

In all likelihood, the wrong lesson will be learned from the current situation regarding Vioxx and Celebrax, and now the FDA will probably become even more conservative about releasing potentially lifesaving drugs for otherwise fatal illnesses.  

A very different way of thinking is critical if cures for diseases requiring a “cocktail” approach are to be effectively found. “Cocktail” components cannot be subjected to the same long-term criteria as single drug regimens for illness,  even though such “cocktail” components would continue to be further tested in the long-term even after initial approval.   

The approach today to dealing with developing drugs for typical, non-fatal illnesses is  “one illness >>> one drug.”  

However otherwise fatal diseases such as cancer and HIV/AIDS require the development of many, many drugs to be used in a “cocktail” --- with no single drug being the magic bullet. For these diseases, the current, outdated approach will not work.  

Today, having the approval of drugs being controlled by a single agency for both the “one illness>>>one drug” approach and the “cocktail” approach is akin to having a single agency to (a) protect the environment; and (b) to seek new oil exploration. It makes no sense, and will not result in either goal being properly handled.   

A NEW AGENCY must be formed immediately to handle the testing and approval of drugs intended for "COCKTAILS" for diseases such as incurable cancers and HIV/AIDS. 

          Even while the FDA may become more conservative in the approval of drugs in light of the Vioxx and Celebrex situation, an agency overseeing the approval of drugs for “anti-cancer cocktails” must make promising drugs available to doctors for front line use as soon as the safety and potential “molecular” effectiveness of a drug has been established --- today … not in 5, 10 or 15 years. A patient who has only months to otherwise live needs all possible options at their disposal once a basic finding of relative safety is found in a drug showing promise at the Molecular level (THIS IS NOT THE SAME as moving a drug through Clinical Trials, which is highly limited in nature and does not speak to “cocktails”. The current concept of CLINICAL TRIALS does not work for “cocktail” development).

 
CHANGING THE DRUG APPROVAL PROCESS FOR CANCER
   

The current FDA policy of requiring years and years of Clinical Trials before a drug can be made available to patients with fatal illnesses also leads to a catch-22 situation in the case of "Molecular Targeted Therapy" (the plan that science is putting all its money on to be the ultimate cure for cancer): for the past 50 or more years, drugs have been typically tested for 10-15 years before approval in order to protect the population. And with non-fatal illnesses this still makes good sense. But in the case of Molecular Targeted Therapy for fatal diseases,  (in essence, the "Cancer Cocktail") cancer patients who are otherwise terminal don't have 10-15 years to wait! They are certain to die before approval. So WHO is being protected?  

“Molecular Targeted” anti-cancer drugs should be made available to patients with fatal illnesses right away without restriction or other qualification just as soon as they have shown relative safety and initial promise.  Initial safety and promise is frequently shown in the first six months, or a year, or two years of testing ... for late stage lung or prostate or ovarian cancer patients, it makes no sense to then keep the drug away from patients for another 2, 4, 6 or 10 years (although ongoing testing to look at all potential safety concerns in the long-run --- while dispensing the drug to late stage cancer patients WITHOUT RESTRICTION --- is certainly valid).

           It is important to understand that this is not the same as advocating "Clinical Trials".  Clinical trials provide a "qualified" patient (one who hasn't taken too many drugs in their prior treatment) with access to a single drug (or sometimes two drugs; or sometimes a placebo) with the stipulation that they go off of ALL OTHER MEDICATION. Since Molecular Targeted Therapy is based on the concept of a "cocktail," Clinical Trials in this area are an oxymoron if it is presented to the patient requiring a "complex cocktail" as an effort to genuinely help to treat them. In reality, the trial is to help the Drug manufacturer demonstrate to the FDA that the drug is safe and has some possible effectiveness. For a patient, truly effective possible treatment requires many such drugs cocktailed ... something that does not happen in a Clinical Trial. Thus, in fact, the current FDA process of cancer drug approval through Clinical Trials is totally antiquated and irrelevant when it comes to the entire science of Molecular Targeted Therapy. It is a backwards step!  

It could be argued by the FDA that if every drug to show promise were immediately made accessible to all patients, it would eliminate access to any "clean" test subjects for Clinical Trials ... since everyone who stood to be a test subject down the road would have already taken the drug as part of their first-line of treatment once the initial safety and possible effectiveness had been demonstrated.  

Technically some could see this as a valid argument, even if grossly unethical; an argument for the greater good of mankind, even if some very ill patients in the coming years must be allowed to die for the sake of science. However after further consideration by even the most Machiavelian, in the case of 21st century Targeted therapy the above argument isn't even valid ;  the argument misses out on an important fact of modern Molecular Targeted Therapy research ---- testing Targeted drugs in isolation for years after initial encouraging results accomplishes little scientifically ... Targeted drugs MUST be tested within Cocktails of many drugs to determine what their ultimate effectiveness will be. The whole theory of Molecular Targeted Therapy is based on synergy.  

To test a single drug by itself (or combined with one other drug) for additional years after it has been shown to have ANY effect on tumors is pointless (other than ongoing safety testing, of course). The ultimate point is to see if the drug is synergistic with other safe and potentially effective Targeted drugs IN A COCKTAIL.  

(This is not to suggest that drugs be necessarily given out for free. "Interim Approval" after safety and potential benefit are demonstrated should cause the drug to be treated like any other approved drug. Of course the entire insurance system will likely need an overhaul to deal with the many, many drugs possibly required in targeted therapy --- this is inevitable in any event.) 

Only front-line use in cocktails will allow the therapy to evolve and become fine-tuned. This will not happen in a "single agent" Clinical Trial setting over 10-15 years. And unlike in Clinical Trials, most patients who have only months to otherwise live would be receiving a therapy that is being undertaken for the primary purpose to trying to offer better all around treatment; treatment that is likely to actually help their disease. 

Testing new drugs only as individual agents might possibly result in an individual drug being rejected when --- in a cocktail --- it might serve its individual purpose well.  

Molecular Targeted therapy is not about any SINGLE drug extending lives. It is about the synergy of the whole cocktail, as long as each individual "battering ram" has been demonstrated to be safe and to have at least some sort of effect on the cancer cells and/or tumors in humans.

          Current FDA policy requires that a potential anti-cancer drug do more than just shrink tumors. To be considered for approval it must demonstrate that in long-term human testing the drug will extend lives, (even if by a month). THIS IS WRONG AND OUTDATED THINKING. Under the whole theory of “Molecular Targeted Therapy”, no single Molecular Targeted drug is expected or intended by itself to extend a life by even a day! If the drug has shown that it will have an impact on cancer cells (shrinking a tumor should be regarded as an out-of-the-park homerun!) then it must be made available to doctors for cocktail use immediately. How many potentially effective low-toxicity anti-cancer cocktail ingredients have already been rejected because all that they did was “shrink” a tumor? If a drug shrinks a tumor, then it is having a PROFOUND effect at the Molecular Level !!!  

Therefore, after initial positive results, Molecular Targeted drugs MUST be made available to front-line doctors to use with interested patients. While the resulting treatment may in fact still be evolving, this does not equate with "experimentation on humans" The relative safety, and possible effectiveness, has already been shown. To continue testing a Targeted drug as a single agent in isolation for years and years is to apply antiquated rules to 21st century approaches. 

Is this approach 100.00% risk free? No, of course not. Nothing is. But is having otherwise fatal, untreatable cancer 100.00% risk free? This approach is highly risk free based on toxicity trials that occur in the first few months of the current 10-15 year testing process. 

And is taking a cancer cocktail of promising targeted drugs a worse bet than sticking with only standard Chemotherapy, which will leave half of all newly diagnosed lung cancer patients dead in 6 - 9 months, and 97% dead by 24 months? So again, who is being protected by the current policy? 

And the re-education of Oncologists must also begin immediately, and on a continuing basis. 

In the words of noted cancer researcher Doctor Larry Weisenthal (www.weisenthal.org):

“What is happening now is that so many new drugs are coming down the pike so fast that there is simply no way to evaluate them in  trials. ... I personally wouldn't hold these new drugs hostage to the really unachievable standard of massive prospective, randomized trials.  I want to see a "cure" for cancer in my lifetime.  I think that "cures" are most likely to come the way it is happening for HIV/AIDS and not the way it happened for syphilis ...   I think that the best chance for discovering the correct "formula" is in having, for example, 1,000 drugs available to cancer doctors all over the world and allowing creativity and insight and the "art of medicine" to enter into the process.”   

The FDA has indeed made recent gestures towards getting drugs for fatal illnesses such as lung cancer approved a little bit earlier than usual, and this is heavily promoted on their web site and in press releases. But the efforts to date fall light years short of what needs to be done ... and quickly ... for the sake of every person who may only have a short time to otherwise live, even as you read this. 

Before it is assumed that this has been written by a PR Firm for the Pharmaceutical industry, it should be made clear that this approach is not proposed to give pharmaceutical companies free reign. Drugs must still be shown to be within reasonable toxicity limits and have shown signs of shrinking tumors or killing cancer cells. And all drugs approved on an "interim basis" after demonstrating low toxicity and some degree of positive effect would still be closely monitored by the FDA and withdrawn if, for any reason, new evidence emerged to suggest a problem. This "interim approval" model was to some degree employed recently in the case of the drug Iressa --- that approach needs to become the rule in all Targeted cancer drug approval rather than the exception. And for otherwise fatal illnesses, these " interim" approvals still need to come years earlier. 

And who would determine the point at which an investigational drug had demonstrated its safety and enough possible positive effect for that drug to be given an "interim approval" for immediate use by cancer patients? Probably a large group of cancer patients should at least act as an advisory council ... a body selected at random from cancer patients across the country; large enough to be statistically free of private interests and influences. 

There is no 5-minute instant solution, but the process of revising the approval process must begin at once. And one thing is for certain: there is not a single member of the FDA who would not hesitate to break every one of their own rules if one of their loved ones otherwise had only months left to live. 

An example of the problem facing an FDA in approving drugs for both non-fatal as well as otherwise fatal illnesses can be seen in the recent problems with the drugs Vioxx and Celebrex. This class of drugs, called COX-2 inhibitors, have been shown to increase the risk of heart attack with long term use. Yet the same drugs have shown that they are potentially highly effective as “cocktail” agents in fighting many lung cancers. In the latter case, then, surely short-term use in order to fight lung cancer may be justified. However it is simply impossible to believe that a single agency (and one under political fire) will be able to effectively administer both sides of the coin.

The December 20, 2004 USA Today reports that ‘the FDA, pressured to get lifesaving drugs to consumers more quickly, rushes drugs to markets. “But patients with sore joints — and other medication choices — shouldn't have to tolerate the same level of risk from their pain reliever as, say, cancer patients do with lifesaving chemotherapy drugs,” (former FDA Chairman) Kessler says.’

The above quote is symptomatic of the problem; the FDA’s  attitude is that anti-cancer drugs are already getting to market more quickly, and with a level of risk higher than pain relievers. This is simply not so, (with the occasional limited exception). And so the danger today is that recent revelations about Vioxx and Celebrex will take the entire approval process for drug agents to be part of an “anti-cancer cocktail” in a backwards direction. The FDA is now so politically tainted with the label of too easily approving drugs, that they will becomes less able to change approval policies  in the way that “cancer cocktail” drugs require. 

URGENTLY NEEDED: A COMPLETELY NEW, LEAN FEDERAL AGENCY CREATED FROM THE GROUND UP; DEDICATED TO RAPIDLY ADVANCING THE CREATION OF 21st CENTURY "COCKTAILS" FOR INCURABLE DISEASES USING A MANHATTEN-PROJECT METHOD OF ACTION 

When IBM, which had dominated the PC market with about 95% of the share, almost lost the entire PC computer market altogether because the whole approach to marketing PCs was different than the historical role of IBM in selling huge business systems, IBM's management wisely spun off a separate company to handle PCs, one that was created from the ground up with a PC mentality. THIS COMPANY WAS NOT ANSWERABLE TO THE PARENT COMPANY, short of mass firings. 

     Using this approach, IBM saved about 5% of the PC market for itself, which is the percentage that most but a handful of PC makers seem to have. Otherwise they'd have lost out on PCs altogether. 

    The FDA was originally set up to PROTECT the American public from drugs that either did not work as claimed, or that were dangerous.  

The FDA was not set up to help in expediting cutting-edge drugs to the pubic as quickly as possible, nor for the designing  or approving of complex cutting-edge treatment protocols.  

Regardless of the current criticism of the FDA’s handling of Vioxx and Celebrex, the mentality of the FDA has always been first and foremost to keep drugs away unless and until every "i" is dotted and every "t" crossed; and with a "one illness - one pill" model..  

The FDA approach, whether it is now made to be more or less conservative, is still 180 degrees wrong in overall principle for the  development of complex "cocktail" treatments. 

In developing a large number of candidate drugs for Molecular Targeted treatment of cancer, an entirely new approach is necessary. Drugs must be evaluated for (i) safety (ie-toxicity) and (ii) whether they show a propensity to damage a molecular target on a cancer cell. At that point, in the case of incurable diseases, they need to be approved and turned over to the front line practitioners in order for many different, complex cocktails to be created with the many forms of cancer. While this would be an evolution, it would not be "experimentation." (The government body could and should then continue longterm safety studies). Each doctor would file reports on their formulations for specific cancers, and the results. The database of tens-of-thousands of evolving treatments, custom formulated on a patient-by-patient basis, would be assessed by computers to look for similar complex combinations that seem most effective for any particular cancer-type. 

This kind of approval process is foreign to the FDA, in spite of misleading claims made on their web site.

YOU CAN'T TEACH AN OLD DOG NEW TRICKS  

     A new body to handle the approval of drugs designed to help treat diseases via cocktail, such as cancer and HIV/AIDS, must be created by Congress and quickly. This body would have no connection with, nor be in any way answerable to, the FDA or NIH or NCI. 

The US Government has stated that the goal is to cure cancer by 2015. Without a major, dynamic new concept to handle approvals and help coordinate formulating of protocols, this is a foolish pipedream being spoken of for political purposes only.  

ADDENDUM 

THE “ACCELERATED ACCESS LAW”  

Further, a major hurdle in the effort of "terminal" cancer patients to stay alive for the longest possible time --- and to hopefully develop cocktails that allow cancer to become rendered a chronic and more manageable disease --- is lack of access to promising drugs that have been undergoing testing for years and years ... even though there exists the "appearance" of a law to provide "expanded access." This "Expanded Access Law" does not work, as in the fine print it makes the compliance of the Drug Companies VOLUNTARY!

The "Expanded Access Law" resulted after the AIDS lobby marched on Washington seeking to gain access to investigational drugs to create a “cocktail” years early --- with a grass roots effort. Although these patients were given what they were seeking because of great media exposure, the law itself was essentially co-opted by requiring voluntary compliance by the drug companies … so that in the future, no patient with a different disease could just snap their fingers and obtain early access to life extending drugs without “drug company approval” --- which undermines the whole intent.

The AIDS patients were young and very rebellious --- their lives were at stake. Although some late stage cancer patients may be struck in their 30s or earlier, most are in their 60s and 70s and 80s --- not as vocal a group. But an organized effort may help to change that if every American Citizen will make their voice heard! Congress must enact real legislation to bring the approval process for drugs that are a part of "Molecular Targeted Therapy," the current approach towards a cure, into line with the 21st Century.  

When Cecily was diagnosed in late October of 2003 with lung cancer, a number of promising new anti-cancer drugs that had been in trials for years --- having established their safety and possible effectiveness years ago --- were eligible to her under the expanded access law because they had completed “Phase III” testing. But in the months prior to the actual FDA approval they were non-the-less unavailable to Cecily and countless other cancer patients after years and years of testing had already been completed: (the  specific drugs: Erbitux and Avastin).  

All of Cecily's requests to the pharmaceutical companies for immediate access on a "compassionate basis" were  declined. All effort to obtain these drugs under the "Expanded Access Law" failed due to a political loophole in the law, which gives final decision-making power to the drug companies. Cecily's requests spanned pharmaceutical companies and Government agencies, including the office of a State Senator.  

        On February 12, 2004, Erbitux was finally approved by the FDA. Erbitux had not been made available to Cecily as of the date of her death on March 3, 2004. She had been told by the pharaceutical companies to wait … that shipment to pharmacies was just weeks away, even as stockpiles of the drug doubtless sat in warehouses.  

        On February 26, 2004, Avastin was approved by the FDA after years of testing.  Avastin as well was not made available to Cecily as of her death on March 3, after months of effort to obtain it. And again, huge inventories were doubtless sitting already manufactured and in warehouses, awaiting the formal product launch ... which occurred less than two weeks after Cecily's passing.  

In spite of the fact that these drugs existed, had been shown to be safe and to have effectiveness years ago, had completed their “Phase III” trials which made them eligible to be released to Cecily months before her passing (and by Febrauray 2004 had even been FDA approved), they were knowingly not made available to Cecily by the pharmaceutical companies before her passing on March 3. She would ask daily if we had obtained them yet.  

            Whom does the “expanded access law” help today?  

One reason that was cited to Cecily for the inability to deliver drugs to her in advance of the formal product launch was that when drugs are so very close to approval and release anyway, all efforts are focused in the direction of that formal product launch.  

For a late stage cancer patient with only a limited time to otherwise live, that is hardly an acceptable answer!  It is an attitude that shows contempt for a law passed by Congress, and contempt for the American public.  

Something in the system --- thought to have been fixed by the AIDS group lobbying Washington just a few years ago --- is still very broken when it comes to "compassionate use" or "accelerated access" to drugs for illnesses other than AIDS. Perhaps the definition of "compassion" in Washington changes from season to season or illness to illness as the political winds blow.

Permission is granted to reproduce this uncopyrighted position paper without the need to credit an author.

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