Guest guest Posted March 28, 2010 Report Share Posted March 28, 2010 Dear Neal, Drugs must go through Clinical Trials Phase I, II and III in order to be placed on the US Market. The company that does this first would have a 20 yr patent from the time they file an IND Investigational New Drug. Once FDA approved, the company then files a NDA or New Drug Application. There have been companies that have gone all the way through Phase III and with an NDA only to NOT market a particular drug! Once on the market there may also be a Phase IV post marketing study. During the 20 yrs NO other company may make the generic of that drug. AFTER the 20 yr patent is up the other companies may make a generic, but it still must go through cinical trials to prove its safety and efficacy. This would be ANDA Abbreviated (shortened) New Drug Application. So even generic drugs MUST go through clinical trials in order to be sold in the US. IF approved by FDA during these trials they can then be marketed. Apparently these two drugs were not approved by the FDA. The NTG has not been proven safe. I hope this helps you to understand what has occured. But if you still have any questions feel free to post them. Jeanetta Mastron CPhT BS Founder/Owner > > I thought all prescription drugs were APPROVED by the FDA. I am wondering > how, or even if, UNAPPROVED drugs can be written? > > See FDA news release below. > > > > > > U.S. Food and Drug Administration > > FDA NEWS RELEASE > > For Immediate Release: March 16, 2010 > > Media Inquiries: Gasparoli, thomas.gasparoli@..., > 301-796-4737 > > Consumer Inquiries: 888-INFO-FDA > > FDA Orders 2 Companies to Stop Marketing Unapproved Nitroglycerin Tablets > > The U.S. Food and Drug Administration today ordered Glenmark Generics of > Mahwah, N.J., and Konec Inc. of Tucson, Ariz., to stop marketing unapproved > nitroglycerin tablets. The tablets are placed under the tongue to relieve > chest pain or to stop a heart attack and are marketed in 0.3 mg, 0.4 mg, and > 0.6 mg dosages. > > The FDA does not anticipate a supply problem for these products. Pfizer Inc. > markets FDA-approved sublingual nitroglycerin tablets in the same strengths > and is able to supply the market with approved products. The FDA also will > work with patient organizations and health care professionals to ensure that > they are aware that an approved product is available. > > The agency's warning letters require Glenmark and Konec to remove the > unapproved tablets as part of the FDA's Unapproved Drugs Initiative1. The > initiative was announced in 2006 to address marketed drugs that had not > received FDA approval. > > The unapproved nitroglycerin tablets have not been proven safe and > effective, and the FDA has not reviewed the quality and labeling of these > products. The unapproved products may differ from approved nitroglycerin > products in some respects, such as formulation and labeling. The FDA has > seen significant quality and efficacy problems with some unapproved > nitroglycerin products. > > " Doctors and patients should know that not all drugs on the market are > backed by an FDA approval, " said Deborah M. Autor, director of the Office of > Compliance at the FDA's Center for Drug Evaluation and Research (CDER). > " This lack of approval undermines the FDA's efforts to ensure that safe and > effective drug products are available to the American public. " > > Consumers using the unapproved products should continue taking their > medication and consult a health care professional for guidance on > alternative treatment options. > > " Consumers are entitled to know that their drugs meet FDA standards, and it > is a priority for the agency to remove from the market unapproved products > that expose consumers to potentially unsafe, ineffective, or poor quality > drugs, " said CDER Director Janet Woodcock, M.D. " The FDA remains committed > to ensuring that prescription drugs obtain the necessary FDA approval, and > we urge companies to actively pursue such approvals. " > > Glenmark and Konec have 15 days to respond to the FDA with a plan for > removing their products from the market. They have 90 days from the date of > the warning letters to stop manufacturing new products and 180 days to stop > further shipment of existing products. > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 28, 2010 Report Share Posted March 28, 2010 there are drugs that have been around since before the FDA. while the number of these drugs are shrinking they are still out there. the FDA has been going through these drugs one at a time until they are all have been approved or off the market.  I thought all prescription drugs were APPROVED by the FDA. I am wondering how, or even if, UNAPPROVED drugs can be written? See FDA news release below. U.S. Food and Drug Administration FDA NEWS RELEASE For Immediate Release: March 16, 2010 Media Inquiries: Gasparoli, thomas.gasparoli@ fda.hhs.gov, 301-796-4737 Consumer Inquiries: 888-INFO-FDA FDA Orders 2 Companies to Stop Marketing Unapproved Nitroglycerin Tablets The U.S. Food and Drug Administration today ordered Glenmark Generics of Mahwah, N.J., and Konec Inc. of Tucson, Ariz., to stop marketing unapproved nitroglycerin tablets. The tablets are placed under the tongue to relieve chest pain or to stop a heart attack and are marketed in 0.3 mg, 0.4 mg, and 0.6 mg dosages. The FDA does not anticipate a supply problem for these products. Pfizer Inc. markets FDA-approved sublingual nitroglycerin tablets in the same strengths and is able to supply the market with approved products. The FDA also will work with patient organizations and health care professionals to ensure that they are aware that an approved product is available. The agency's warning letters require Glenmark and Konec to remove the unapproved tablets as part of the FDA's Unapproved Drugs Initiative1. The initiative was announced in 2006 to address marketed drugs that had not received FDA approval. The unapproved nitroglycerin tablets have not been proven safe and effective, and the FDA has not reviewed the quality and labeling of these products. The unapproved products may differ from approved nitroglycerin products in some respects, such as formulation and labeling. The FDA has seen significant quality and efficacy problems with some unapproved nitroglycerin products. " Doctors and patients should know that not all drugs on the market are backed by an FDA approval, " said Deborah M. Autor, director of the Office of Compliance at the FDA's Center for Drug Evaluation and Research (CDER). " This lack of approval undermines the FDA's efforts to ensure that safe and effective drug products are available to the American public. " Consumers using the unapproved products should continue taking their medication and consult a health care professional for guidance on alternative treatment options. " Consumers are entitled to know that their drugs meet FDA standards, and it is a priority for the agency to remove from the market unapproved products that expose consumers to potentially unsafe, ineffective, or poor quality drugs, " said CDER Director Janet Woodcock, M.D. " The FDA remains committed to ensuring that prescription drugs obtain the necessary FDA approval, and we urge companies to actively pursue such approvals. " Glenmark and Konec have 15 days to respond to the FDA with a plan for removing their products from the market. They have 90 days from the date of the warning letters to stop manufacturing new products and 180 days to stop further shipment of existing products. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 28, 2010 Report Share Posted March 28, 2010 Neal, Karin is referring to the 'FDA's Unapproved Drugs Initiative' that is mentioned in the document. The process I desribed is the process that these and other drugs are lacking and therefore are not FDA approved drugs and are being removed from the market. IF they were approved drugs the process would be called a 'recall', but since they are not approved drugs it is an FDA order. The companies must comply. Respectfully, Jeanetta Mastron CPhT BS Founder/Owner I thought all prescription drugs were APPROVED by the FDA. I am wondering how, or even if, UNAPPROVED drugs can be written? See FDA news release below. U.S. Food and Drug Administration FDA NEWS RELEASE For Immediate Release: March 16, 2010 Media Inquiries: Gasparoli, thomas.gasparoli@ fda.hhs.gov, 301-796-4737 Consumer Inquiries: 888-INFO-FDA FDA Orders 2 Companies to Stop Marketing Unapproved Nitroglycerin Tablets The U.S. Food and Drug Administration today ordered Glenmark Generics of Mahwah, N.J., and Konec Inc. of Tucson, Ariz., to stop marketing unapproved nitroglycerin tablets. The tablets are placed under the tongue to relieve chest pain or to stop a heart attack and are marketed in 0.3 mg, 0.4 mg, and 0.6 mg dosages. The FDA does not anticipate a supply problem for these products. Pfizer Inc. markets FDA-approved sublingual nitroglycerin tablets in the same strengths and is able to supply the market with approved products. The FDA also will work with patient organizations and health care professionals to ensure that they are aware that an approved product is available. The agency's warning letters require Glenmark and Konec to remove the unapproved tablets as part of the FDA's Unapproved Drugs Initiative1. The initiative was announced in 2006 to address marketed drugs that had not received FDA approval. The unapproved nitroglycerin tablets have not been proven safe and effective, and the FDA has not reviewed the quality and labeling of these products. The unapproved products may differ from approved nitroglycerin products in some respects, such as formulation and labeling. The FDA has seen significant quality and efficacy problems with some unapproved nitroglycerin products. " Doctors and patients should know that not all drugs on the market are backed by an FDA approval, " said Deborah M. Autor, director of the Office of Compliance at the FDA's Center for Drug Evaluation and Research (CDER). " This lack of approval undermines the FDA's efforts to ensure that safe and effective drug products are available to the American public. " Consumers using the unapproved products should continue taking their medication and consult a health care professional for guidance on alternative treatment options. " Consumers are entitled to know that their drugs meet FDA standards, and it is a priority for the agency to remove from the market unapproved products that expose consumers to potentially unsafe, ineffective, or poor quality drugs, " said CDER Director Janet Woodcock, M.D. " The FDA remains committed to ensuring that prescription drugs obtain the necessary FDA approval, and we urge companies to actively pursue such approvals. " Glenmark and Konec have 15 days to respond to the FDA with a plan for removing their products from the market. They have 90 days from the date of the warning letters to stop manufacturing new products and 180 days to stop further shipment of existing products. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted August 8, 2010 Report Share Posted August 8, 2010 That FDA link i found on http://www.jimhumble.com/ linked down below under (The MMS Newsletter signup is here) click on that it takes you to the FDA, seems kind of funny finding it there. Maybe the whole site is the FDA? Quote Link to comment Share on other sites More sharing options...
Guest guest Posted August 8, 2010 Report Share Posted August 8, 2010 yes, like the massive recall they should be doing for the mercury in high fructose corn syrup. From: mfrreman@...Date: Sun, 8 Aug 2010 14:15:42 +0000Subject: [ ] Re: fda Sodium Chlorite may become as controversial as marijuana for alternative medicine. To think the state police could knock on my door for MMS? Wish the FDA was as concerned about the gulf of mexico, and so many other serious health issues. > > > That FDA link i found on http://www.jimhumble.com/ linked down below under (The MMS Newsletter signup is here) click on that it takes you to the FDA, seems kind of funny finding it there. Maybe the whole site is the FDA? > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 10, 2011 Report Share Posted January 10, 2011 Dr. Furman, I totally agree with your arguments; the FDA is just another huge inefficient government bureaucracy. I would support any grass roots movement to change the system. Hollie Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 10, 2011 Report Share Posted January 10, 2011 Karl, I think you are missing Dr Furman's point. The new kinase inhibitors apparently produce benefit without a response. Because there is a persisting lymphocytosis, the shrinkage of spleen and lymph nodes count for nothing. They are labelled as non-responders, yet potentially such patients may stabilize their disease for many years. Merely having CLL does not necessarily harm people. Terry Hamblin MD In a message dated 10/01/2011 17:03:37 GMT Standard Time, karls@... writes: Dr. Furman, Of course, I know that you can't have a benefit without a response, what I am saying is that a response doesn't mean you have a benefit - many drugs induce responses but are found to be too toxic, or the response doesn't last, or doesn't translate into living longer or better when weighed against the toxicities (immediate or delayed). My point is that changes to FDA policy would apply to ALL drugs for serious disease - Should we lower standard for review because some minority of drugs may prove to be effective - achieve responses with low toxicity? or discuss in a public way the trial design needed to demonstrate the worth of such drugs? ly, I can't agree with with the Abigail proposal: that just releasing hundreds of drugs into the market place based on phase I results could be helpful patients -- or that it would receive the support of most physicians or the industry. I expect most sponsors would oppose the law change - assuming it would not lead to insurance coverage and for good reason. The personal injury trial lawyers would love it! Regarding patient access in the meantime, an important issue, why aren't the sponsors of such drugs setting up expanded access trials now?, for trial ineligible patients, which could be used also to support approval? .... Recent changes to policy allow for sponsors to charge for expanded access. I recall that the sponsors of Gleevec and Bexxar made use of the Expanded access trials and that that data was eventually used to help support bexxar approval - which (based on advisory committee text) was delayed because the sponsor changed manufacturing methods .... a sort of digression, but worth noting because it reminds that phase I approvals would require sponsor to also get up to speed to manufacture on a large scale -- assuming they'd participate - I doubt most would. Excuse my venting, but I get concerned when patient advocacy of this type is promoted without without details about the sponsor's dispute with FDA. Karl > > > > > > There is a tendency evidenced in government to control what happens to paying for drugs, especially cancer drugs. > > > > > > There is a new effort by the head of Medicare ( Berwick) to limit coverage for cancer drugs. This is similar to the UK's 'NICE' which stands for National Institute for Clinical Excellence. It's charged with denying coverage for drugs based on expense. > > > > > > New drugs are often very expensive. Drug companies want to recoup the $800 million it takes to approve a drug, and they want to make as much money as they can while they hold the patent. > > > > > > The government wants to restrict coverage, to spare costs. > > > > > > This will be the overriding consideration from now on. > > > > > > If CAL-101 and other drugs fall by the wayside, that's just too bad. > > > > > > We Americans have been spoiled by a hands-off policy of drug approval. That's all changed now. > > > > > > Unless a drug is specifically approved for a disease, it might not be paid for. Off-label use may be going away for good. > > > > > > > > > > > > > > > Sat Jan 1, 2011 11:16 am (PST) > > > > > > > > > The problem is much more complicated than this. The FDA approvals are based primarily on not just benefit. The two criteria used are: > > > > > > 1)greater benefit than the currently approved therapies (requires head to head comparisons) > > > > > > 2)unmet medical need (nothing approved to compare with) > > > > > > > > > > > > The FDA has suggested that it will not allow any drugs to be further approved for CLL using the unmet medical need criteria. This is how alemtuzumab and ofatumumab have gained approval. Thus, a trial of drug X in patients who have disease that is refractory to fludarabine, bendamustine, alemtuzumab, and ofatumumab will not lead to approval. Even if this agent (like PCI-32765 or CAL-101) has a 90% rate of clinical benefit / response. > > > > > > > > > > > > Likewise, for some very unexplicable reason, the FDA will not allow multiple drugs to be approved at the same indication. There are 25 different anti-hypertensives and 10 different cholesterol lowering agents. They did not have to prove themselves better than the currently available therapies. Just that they were efficacious. Why not the same thing for oncology drugs? > > > > > > > > > > > > Why can we not just show CAL-101 benefit patients and get it approved? > > > > > > > > > > > > Additionally, the FDA will not approve an agent that is equally effective, but less toxic over the current standard of care. This would require a large study secondary to statistical reasons, but once done, would be a much easier means to approve these new agents. > > > > > > > > > > > > These are just two of the glaring issues where the FDA does not function in a manner that is in patients' best interests. People have been complaining or criticizing the pharmaceutical companies, physicians, etc., but all anyone wants is to get excellent agents to the market as quickly and safely as possible. A less burdensome system would also encourage more novel drug development. It could be a simple as once a drug shows efficacy and safety, that there be programs to allow physicians to use these agents in all patients while closely monitoring further data on safey and efficacy. Would it not be great if anyone who needed CAL-101 or PCI-32765 could get it from their local oncologist? > > > > > > > > > > > > I think this is a good opportunity to build a grassroots effort to change the way the FDA makes these decisions. Let us propose starting a campaign to address these inadequacies in drug development. This is something that CIG is very well situated to spearhead. Let me know your thoughts! > > > > > > > > > > > > Rick Furman, MD > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 10, 2011 Report Share Posted January 10, 2011 First, it is not true that FDA requires superiority to another drug - that a safer but otherwise equivalent drug could not win approval. (I have already posted the regulations to support my opinion including a paper that shows examples. An obvious benefit for such a drug: it would be available to more patients because of its more favorable toxicity profile. Second, ACA (Affordable Care Act) has a provision for encouraging comparative effectiveness research, but the basis for comparisions - is on effectiveness, NOT costs. Which. btw. is needed to guide medical decision making - is good for patients. Lack of such information leading to trial and error prescribing - and often much unproductive toxicity. Regarding FDA evaluation of drugs, the Critical Path document shows that the rate-limiting factor is the conduct of clinical trials (including enrollment). The review time - following submission of the data to FDA and its decision occurs in 7 to 14 months. The document cites also the main reason for application failures: most new drugs are too toxic at active doses. (Net harm.) Regarding the Abigail Alliance petition: We need to be mindful that drug safety cannot be determined independent of efficacy. All drugs have toxicities (even aspirin), particularly cancer drugs, thus phase I cancer studies (which every expert knows cannot find for efficacy) cannot demonstrate safety if defined as benefits outweigh toxicities. You may recall how many phase I studies report: the toxicities were acceptable at the active dose -- meaning acceptable relative to other cancer drugs and so additional investigation is acceptable but certainly not approval ... and if approved based on this level of evidence (as Abigail promotes) would lead to hundreds of such drugs on the market - and doctors with the burden of having to report and test for toxicities as is is done in phase II. Which would lead to law suits against the companies when things went wrong. Which would never be covered by insurance companies ... etc. In short, a terrible idea. Lastly, don't overestimate the meaning of " response " in media reports on new drugs. Response does not mean benefit necessarily. Lots are drugs can produce responses but a minority do so while also helping patients to live better or longer. Karl > > There is a tendency evidenced in government to control what happens to paying for drugs, especially cancer drugs. > > There is a new effort by the head of Medicare ( Berwick) to limit coverage for cancer drugs. This is similar to the UK's 'NICE' which stands for National Institute for Clinical Excellence. It's charged with denying coverage for drugs based on expense. > > New drugs are often very expensive. Drug companies want to recoup the $800 million it takes to approve a drug, and they want to make as much money as they can while they hold the patent. > > The government wants to restrict coverage, to spare costs. > > This will be the overriding consideration from now on. > > If CAL-101 and other drugs fall by the wayside, that's just too bad. > > We Americans have been spoiled by a hands-off policy of drug approval. That's all changed now. > > Unless a drug is specifically approved for a disease, it might not be paid for. Off-label use may be going away for good. > > > > > Sat Jan 1, 2011 11:16 am (PST) > > > The problem is much more complicated than this. The FDA approvals are based primarily on not just benefit. The two criteria used are: > > 1)greater benefit than the currently approved therapies (requires head to head comparisons) > > 2)unmet medical need (nothing approved to compare with) > > > > The FDA has suggested that it will not allow any drugs to be further approved for CLL using the unmet medical need criteria. This is how alemtuzumab and ofatumumab have gained approval. Thus, a trial of drug X in patients who have disease that is refractory to fludarabine, bendamustine, alemtuzumab, and ofatumumab will not lead to approval. Even if this agent (like PCI-32765 or CAL-101) has a 90% rate of clinical benefit / response. > > > > Likewise, for some very unexplicable reason, the FDA will not allow multiple drugs to be approved at the same indication. There are 25 different anti-hypertensives and 10 different cholesterol lowering agents. They did not have to prove themselves better than the currently available therapies. Just that they were efficacious. Why not the same thing for oncology drugs? > > > > Why can we not just show CAL-101 benefit patients and get it approved? > > > > Additionally, the FDA will not approve an agent that is equally effective, but less toxic over the current standard of care. This would require a large study secondary to statistical reasons, but once done, would be a much easier means to approve these new agents. > > > > These are just two of the glaring issues where the FDA does not function in a manner that is in patients' best interests. People have been complaining or criticizing the pharmaceutical companies, physicians, etc., but all anyone wants is to get excellent agents to the market as quickly and safely as possible. A less burdensome system would also encourage more novel drug development. It could be a simple as once a drug shows efficacy and safety, that there be programs to allow physicians to use these agents in all patients while closely monitoring further data on safey and efficacy. Would it not be great if anyone who needed CAL-101 or PCI-32765 could get it from their local oncologist? > > > > I think this is a good opportunity to build a grassroots effort to change the way the FDA makes these decisions. Let us propose starting a campaign to address these inadequacies in drug development. This is something that CIG is very well situated to spearhead. Let me know your thoughts! > > > > Rick Furman, MD > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 10, 2011 Report Share Posted January 10, 2011 But do remember not to underestimate " response " for some of the drugs we are discussing. The PCI-32765 and CAL-101 patients, even with complete regression of lymphadenopathy may not qualify as responders because of the lymphocytosis. These patients are clearly benefiting even as non-responders. Rick Furman > > > > There is a tendency evidenced in government to control what happens to paying for drugs, especially cancer drugs. > > > > There is a new effort by the head of Medicare ( Berwick) to limit coverage for cancer drugs. This is similar to the UK's 'NICE' which stands for National Institute for Clinical Excellence. It's charged with denying coverage for drugs based on expense. > > > > New drugs are often very expensive. Drug companies want to recoup the $800 million it takes to approve a drug, and they want to make as much money as they can while they hold the patent. > > > > The government wants to restrict coverage, to spare costs. > > > > This will be the overriding consideration from now on. > > > > If CAL-101 and other drugs fall by the wayside, that's just too bad. > > > > We Americans have been spoiled by a hands-off policy of drug approval. That's all changed now. > > > > Unless a drug is specifically approved for a disease, it might not be paid for. Off-label use may be going away for good. > > > > > > > > > > Sat Jan 1, 2011 11:16 am (PST) > > > > > > The problem is much more complicated than this. The FDA approvals are based primarily on not just benefit. The two criteria used are: > > > > 1)greater benefit than the currently approved therapies (requires head to head comparisons) > > > > 2)unmet medical need (nothing approved to compare with) > > > > > > > > The FDA has suggested that it will not allow any drugs to be further approved for CLL using the unmet medical need criteria. This is how alemtuzumab and ofatumumab have gained approval. Thus, a trial of drug X in patients who have disease that is refractory to fludarabine, bendamustine, alemtuzumab, and ofatumumab will not lead to approval. Even if this agent (like PCI-32765 or CAL-101) has a 90% rate of clinical benefit / response. > > > > > > > > Likewise, for some very unexplicable reason, the FDA will not allow multiple drugs to be approved at the same indication. There are 25 different anti-hypertensives and 10 different cholesterol lowering agents. They did not have to prove themselves better than the currently available therapies. Just that they were efficacious. Why not the same thing for oncology drugs? > > > > > > > > Why can we not just show CAL-101 benefit patients and get it approved? > > > > > > > > Additionally, the FDA will not approve an agent that is equally effective, but less toxic over the current standard of care. This would require a large study secondary to statistical reasons, but once done, would be a much easier means to approve these new agents. > > > > > > > > These are just two of the glaring issues where the FDA does not function in a manner that is in patients' best interests. People have been complaining or criticizing the pharmaceutical companies, physicians, etc., but all anyone wants is to get excellent agents to the market as quickly and safely as possible. A less burdensome system would also encourage more novel drug development. It could be a simple as once a drug shows efficacy and safety, that there be programs to allow physicians to use these agents in all patients while closely monitoring further data on safey and efficacy. Would it not be great if anyone who needed CAL-101 or PCI-32765 could get it from their local oncologist? > > > > > > > > I think this is a good opportunity to build a grassroots effort to change the way the FDA makes these decisions. Let us propose starting a campaign to address these inadequacies in drug development. This is something that CIG is very well situated to spearhead. Let me know your thoughts! > > > > > > > > Rick Furman, MD > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 10, 2011 Report Share Posted January 10, 2011 Dr. Furman, Of course, I know that you can't have a benefit without a response, what I am saying is that a response doesn't mean you have a benefit - many drugs induce responses but are found to be too toxic, or the response doesn't last, or doesn't translate into living longer or better when weighed against the toxicities (immediate or delayed). My point is that changes to FDA policy would apply to ALL drugs for serious disease - Should we lower standard for review because some minority of drugs may prove to be effective - achieve responses with low toxicity? or discuss in a public way the trial design needed to demonstrate the worth of such drugs? ly, I can't agree with with the Abigail proposal: that just releasing hundreds of drugs into the market place based on phase I results could be helpful patients -- or that it would receive the support of most physicians or the industry. I expect most sponsors would oppose the law change - assuming it would not lead to insurance coverage and for good reason. The personal injury trial lawyers would love it! Regarding patient access in the meantime, an important issue, why aren't the sponsors of such drugs setting up expanded access trials now?, for trial ineligible patients, which could be used also to support approval? .... Recent changes to policy allow for sponsors to charge for expanded access. I recall that the sponsors of Gleevec and Bexxar made use of the Expanded access trials and that that data was eventually used to help support bexxar approval - which (based on advisory committee text) was delayed because the sponsor changed manufacturing methods .... a sort of digression, but worth noting because it reminds that phase I approvals would require sponsor to also get up to speed to manufacture on a large scale -- assuming they'd participate - I doubt most would. Excuse my venting, but I get concerned when patient advocacy of this type is promoted without without details about the sponsor's dispute with FDA. Karl > > > > > > There is a tendency evidenced in government to control what happens to paying for drugs, especially cancer drugs. > > > > > > There is a new effort by the head of Medicare ( Berwick) to limit coverage for cancer drugs. This is similar to the UK's 'NICE' which stands for National Institute for Clinical Excellence. It's charged with denying coverage for drugs based on expense. > > > > > > New drugs are often very expensive. Drug companies want to recoup the $800 million it takes to approve a drug, and they want to make as much money as they can while they hold the patent. > > > > > > The government wants to restrict coverage, to spare costs. > > > > > > This will be the overriding consideration from now on. > > > > > > If CAL-101 and other drugs fall by the wayside, that's just too bad. > > > > > > We Americans have been spoiled by a hands-off policy of drug approval. That's all changed now. > > > > > > Unless a drug is specifically approved for a disease, it might not be paid for. Off-label use may be going away for good. > > > > > > > > > > > > > > > Sat Jan 1, 2011 11:16 am (PST) > > > > > > > > > The problem is much more complicated than this. The FDA approvals are based primarily on not just benefit. The two criteria used are: > > > > > > 1)greater benefit than the currently approved therapies (requires head to head comparisons) > > > > > > 2)unmet medical need (nothing approved to compare with) > > > > > > > > > > > > The FDA has suggested that it will not allow any drugs to be further approved for CLL using the unmet medical need criteria. This is how alemtuzumab and ofatumumab have gained approval. Thus, a trial of drug X in patients who have disease that is refractory to fludarabine, bendamustine, alemtuzumab, and ofatumumab will not lead to approval. Even if this agent (like PCI-32765 or CAL-101) has a 90% rate of clinical benefit / response. > > > > > > > > > > > > Likewise, for some very unexplicable reason, the FDA will not allow multiple drugs to be approved at the same indication. There are 25 different anti-hypertensives and 10 different cholesterol lowering agents. They did not have to prove themselves better than the currently available therapies. Just that they were efficacious. Why not the same thing for oncology drugs? > > > > > > > > > > > > Why can we not just show CAL-101 benefit patients and get it approved? > > > > > > > > > > > > Additionally, the FDA will not approve an agent that is equally effective, but less toxic over the current standard of care. This would require a large study secondary to statistical reasons, but once done, would be a much easier means to approve these new agents. > > > > > > > > > > > > These are just two of the glaring issues where the FDA does not function in a manner that is in patients' best interests. People have been complaining or criticizing the pharmaceutical companies, physicians, etc., but all anyone wants is to get excellent agents to the market as quickly and safely as possible. A less burdensome system would also encourage more novel drug development. It could be a simple as once a drug shows efficacy and safety, that there be programs to allow physicians to use these agents in all patients while closely monitoring further data on safey and efficacy. Would it not be great if anyone who needed CAL-101 or PCI-32765 could get it from their local oncologist? > > > > > > > > > > > > I think this is a good opportunity to build a grassroots effort to change the way the FDA makes these decisions. Let us propose starting a campaign to address these inadequacies in drug development. This is something that CIG is very well situated to spearhead. Let me know your thoughts! > > > > > > > > > > > > Rick Furman, MD > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 10, 2011 Report Share Posted January 10, 2011 I see. Thank you. In that case, I believe the sponsor should focus on convening independent experts and patient representatives to discuss with FDA what trial design (endpoints, eligibility, response criteria, etc) are needed to demonstrate this kind of response and possible benefit to patients. Showing that a drug can delay (with minimal toxicity) time to progression, for example, could well be persuasive in a population not in need of treatment. I expect that such a study could ethically randomize to the agent versus observation in this setting, because no treatment is needed. A crossover could be allowed - for those who progress in the observation group. Could FDA approve for marketing based on such data? I truly expect so, but the decision (you don't know how persuasive until you test) would depend on the toxicities and the magnitude of the benefit - does it delay PFS for a few months or years ... with consideration of possible offsetting toxicities and hits on quality of life ... as you know (but for the benefit of those following the discussion). Anyhow, my concern is that a valid issue about trial design has somehow morphed into let's trash the FDA and do away with standards for evaluating new drugs. No? I feel strongly about this issue because I've spent the better part of the last 12 years following and sometimes participating in the review process and from that experence I have now much respect for the process, (which I didn't have going in - based on abundant misinformation about FDA on the internet.) For anyone deeply suspicious of the process I recommend that you read carefully the transcipts of any advisory committee review of a cancer drug ... you may disagree with a committee's decision, but I expect you will see that the process has integrity, that the issues are complex, and that patient protection is the primary concern. Karl > > > > > > > > There is a tendency evidenced in government to control what happens > to paying for drugs, especially cancer drugs. > > > > > > > > There is a new effort by the head of Medicare ( Berwick) to > limit coverage for cancer drugs. This is similar to the UK's 'NICE' which > stands for National Institute for Clinical Excellence. It's charged with > denying coverage for drugs based on expense. > > > > > > > > New drugs are often very expensive. Drug companies want to recoup > the $800 million it takes to approve a drug, and they want to make as much > money as they can while they hold the patent. > > > > > > > > The government wants to restrict coverage, to spare costs. > > > > > > > > This will be the overriding consideration from now on. > > > > > > > > If CAL-101 and other drugs fall by the wayside, that's just too bad. > > > > > > > > > We Americans have been spoiled by a hands-off policy of drug > approval. That's all changed now. > > > > > > > > Unless a drug is specifically approved for a disease, it might not > be paid for. Off-label use may be going away for good. > > > > > > > > > > > > > > > > > > > > Sat Jan 1, 2011 11:16 am (PST) > > > > > > > > > > > > The problem is much more complicated than this. The FDA approvals > are based primarily on not just benefit. The two criteria used are: > > > > > > > > 1)greater benefit than the currently approved therapies (requires > head to head comparisons) > > > > > > > > 2)unmet medical need (nothing approved to compare with) > > > > > > > > > > > > > > > > The FDA has suggested that it will not allow any drugs to be further > approved for CLL using the unmet medical need criteria. This is how > alemtuzumab and ofatumumab have gained approval. Thus, a trial of drug X in > patients who have disease that is refractory to fludarabine, bendamustine, > alemtuzumab, and ofatumumab will not lead to approval. Even if this agent (like > PCI-32765 or CAL-101) has a 90% rate of clinical benefit / response. > > > > > > > > > > > > > > > > Likewise, for some very unexplicable reason, the FDA will not allow > multiple drugs to be approved at the same indication. There are 25 > different anti-hypertensives and 10 different cholesterol lowering agents. They did > not have to prove themselves better than the currently available > therapies. Just that they were efficacious. Why not the same thing for oncology > drugs? > > > > > > > > > > > > > > > > Why can we not just show CAL-101 benefit patients and get it > approved? > > > > > > > > > > > > > > > > Additionally, the FDA will not approve an agent that is equally > effective, but less toxic over the current standard of care. This would require > a large study secondary to statistical reasons, but once done, would be a > much easier means to approve these new agents. > > > > > > > > > > > > > > > > These are just two of the glaring issues where the FDA does not > function in a manner that is in patients' best interests. People have been > complaining or criticizing the pharmaceutical companies, physicians, etc., but > all anyone wants is to get excellent agents to the market as quickly and > safely as possible. A less burdensome system would also encourage more novel > drug development. It could be a simple as once a drug shows efficacy and > safety, that there be programs to allow physicians to use these agents in all > patients while closely monitoring further data on safey and efficacy. Would > it not be great if anyone who needed CAL-101 or PCI-32765 could get it > from their local oncologist? > > > > > > > > > > > > > > > > I think this is a good opportunity to build a grassroots effort to > change the way the FDA makes these decisions. Let us propose starting a > campaign to address these inadequacies in drug development. This is something > that CIG is very well situated to spearhead. Let me know your thoughts! > > > > > > > > > > > > > > > > Rick Furman, MD > > > > > > > > > > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 18, 2011 Report Share Posted January 18, 2011 Karl, Thanks Karl for the recent e-mails between you and I. I understand your position to a point. And that point is where there is no health to protect. I cringe when I see you continually defend a system that should be and can be improved. Publically Karl, what I'd like you to answer to the group is this. What do you tell the dying patient who has tryed everything with out success? Is " Go home and die " appropreate for you? Cause its not for me. In today's world where medicine is good enough to let us know when we truly are on the verge of death, can't you agree that at that time, when there is no health to protect, a well informed patient should have the ability to choose any meds that he and his research team feels could offer hope? If you can't accept this position then you are simply saying too bad, go home, and die, or ??? what are you saying then to someone who has tried everything with no success?? Answer me that please. When the only upcoming event is death, do I really care about possibilities of toxicity? If nothing else, allow me.... the dying patient, the chance to have my death mean something by giving me a shot at early research with no liability to the research team. Guinea Pig?? Of course...just as if I were in a phase I Clinical trial although with risks many times larger against me. At least my death now has a bit more value than just my life accomplishments. Or better said, one last accomplishment for those who follow while still providing a tiny tiny ray of hope. My body, my choice!! And while it will take creativity to do it right, it can be done and what I would give to see an FDA that at least tries to make that happen. HINT HINT Hint..... When you get there, the black market, last ditch treatments in Mexico or else where will dissappear. Those people will be properly served by their fellow citizens at the FDA. Givepatientsafightingchance.com may not be the answer, but it does express ideas of how it could happen. Awaiting your answer Karl. Respectfully, Leo ____________________________________ From: karls@... Reply-to: Sent: 1/10/2011 6:55:30 A.M. Pacific Standard Time Subj: Re: FDA First, it is not true that FDA requires superiority to another drug - that a safer but otherwise equivalent drug could not win approval. (I have already posted the regulations to support my opinion including a paper that shows examples. An obvious benefit for such a drug: it would be available to more patients because of its more favorable toxicity profile. Second, ACA (Affordable Care Act) has a provision for encouraging comparative effectiveness research, but the basis for comparisions - is on effectiveness, NOT costs. Which. btw. is needed to guide medical decision making - is good for patients. Lack of such information leading to trial and error prescribing - and often much unproductive toxicity. Regarding FDA evaluation of drugs, the Critical Path document shows that the rate-limiting factor is the conduct of clinical trials (including enrollment). The review time - following submission of the data to FDA and its decision occurs in 7 to 14 months. The document cites also the main reason for application failures: most new drugs are too toxic at active doses. (Net harm.) Regarding the Abigail Alliance petition: We need to be mindful that drug safety cannot be determined independent of efficacy. All drugs have toxicities (even aspirin), particularly cancer drugs, thus phase I cancer studies (which every expert knows cannot find for efficacy) cannot demonstrate safety if defined as benefits outweigh toxicities. You may recall how many phase I studies report: the toxicities were acceptable at the active dose -- meaning acceptable relative to other cancer drugs and so additional investigation is acceptable but certainly not approval ... and if approved based on this level of evidence (as Abigail promotes) would lead to hundreds of such drugs on the market - and doctors with the burden of having to report and test for toxicities as is is done in phase II. Which would lead to law suits against the companies when things went wrong. Which would never be covered by insurance companies ... etc. In short, a terrible idea. Lastly, don't overestimate the meaning of " response " in media reports on new drugs. Response does not mean benefit necessarily. Lots are drugs can produce responses but a minority do so while also helping patients to live better or longer. Karl > > There is a tendency evidenced in government to control what happens to paying for drugs, especially cancer drugs. > > There is a new effort by the head of Medicare ( Berwick) to limit coverage for cancer drugs. This is similar to the UK's 'NICE' which stands for National Institute for Clinical Excellence. It's charged with denying coverage for drugs based on expense. > > New drugs are often very expensive. Drug companies want to recoup the $800 million it takes to approve a drug, and they want to make as much money as they can while they hold the patent. > > The government wants to restrict coverage, to spare costs. > > This will be the overriding consideration from now on. > > If CAL-101 and other drugs fall by the wayside, that's just too bad. > > We Americans have been spoiled by a hands-off policy of drug approval. That's all changed now. > > Unless a drug is specifically approved for a disease, it might not be paid for. Off-label use may be going away for good. > > > > > Sat Jan 1, 2011 11:16 am (PST) > > > The problem is much more complicated than this. The FDA approvals are based primarily on not just benefit. The two criteria used are: > > 1)greater benefit than the currently approved therapies (requires head to head comparisons) > > 2)unmet medical need (nothing approved to compare with) > > > > The FDA has suggested that it will not allow any drugs to be further approved for CLL using the unmet medical need criteria. This is how alemtuzumab and ofatumumab have gained approval. Thus, a trial of drug X in patients who have disease that is refractory to fludarabine, bendamustine, alemtuzumab, and ofatumumab will not lead to approval. Even if this agent (like PCI-32765 or CAL-101) has a 90% rate of clinical benefit / response. > > > > Likewise, for some very unexplicable reason, the FDA will not allow multiple drugs to be approved at the same indication. There are 25 different anti-hypertensives and 10 different cholesterol lowering agents. They did not have to prove themselves better than the currently available therapies. Just that they were efficacious. Why not the same thing for oncology drugs? > > > > Why can we not just show CAL-101 benefit patients and get it approved? > > > > Additionally, the FDA will not approve an agent that is equally effective, but less toxic over the current standard of care. This would require a large study secondary to statistical reasons, but once done, would be a much easier means to approve these new agents. > > > > These are just two of the glaring issues where the FDA does not function in a manner that is in patients' best interests. People have been complaining or criticizing the pharmaceutical companies, physicians, etc., but all anyone wants is to get excellent agents to the market as quickly and safely as possible. A less burdensome system would also encourage more novel drug development. It could be a simple as once a drug shows efficacy and safety, that there be programs to allow physicians to use these agents in all patients while closely monitoring further data on safey and efficacy. Would it not be great if anyone who needed CAL-101 or PCI-32765 could get it from their local oncologist? > > > > I think this is a good opportunity to build a grassroots effort to change the way the FDA makes these decisions. Let us propose starting a campaign to address these inadequacies in drug development. This is something that CIG is very well situated to spearhead. Let me know your thoughts! > > > > Rick Furman, MD > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 19, 2011 Report Share Posted January 19, 2011 A dental patient of mine has two children, ages 18 and 23, with cystic fibrosis. Over the years, they have received " optimal " treatment, the latest treatments, etc, for the condition. They have severe pulmonary pathology, one child has had an upper lobe of one lung removed, etc. Every time they get sick from a cold, flu, allergy, their lives are in jeopardy and they suffer long relapses and often need hospitalization for extended periods. With a bent toward research, I told the mother I'd dig into the subject matter and try to find other opinions for the kids. I contacted high level researchers, both clinicians and bench scientists. I found out there were some excellent treatment modalities, things that could make significant differences. I hit the stonewall. These researchers feared liability more than anything to even discuss new treatments that were not FDA approved. Approval is not an absolute term the FDA uses, by the way. This fear is justified in some cases, perhaps not in many others. When you tell a researcher the kids are dying, that something must be done, you get nothing, nada, zilch. Nobody wants to go out on any limb. Let the kids die..... Obviously, with potentially toxic materials, dosages have to be worked out carefully, along with the rest of the protocols. Any researcher who has not been turned down for a grant, I want to shake his hand. Grants are often very political entities and researchers tear their hair out when they fail to secure them. In the case of dire straits cases, like the ones I mentioned, do you seek to use materials not fully tested but showing excellent results in animal models? Who assumes the risk of liability? Are the ambulance chasers near by, just waiting for somebody to slip and cause a problem? If we could back off on liability assuming the patients know the risks, why not use new materials and techniques if death is on the doorstep? These questions must be asked before progress could be expected. My wife is a university researcher and faces these questions all the time. But, power blocks exist in the research game and obtaining grants is often greatly hindered by these often cronyistic manifestations. Research is hindered by far more things than mere biology. The problems experienced by the kids with CF are very similar with the problems people with CLL have regarding use of materials not fully tested, etc. It is far more than mere FDA that fuels these sorts of conundrums. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 19, 2011 Report Share Posted January 19, 2011 No question but that if logic prevailed, there would be room for compassionate use of untested drugs in such circumstances but there is a long history of horrendous abuse with human subjects. Just Google Tuskegee and read about the syphilis trials. There are numerous examples of abuse and researchers pay the price in stricter controls. Some abuses have been government sponsored. These are not the ravings of a conspiracy theorist but documented facts. The overwhelming majority of researchers regardless of affiliation are ethical scientists who dedicate their lives to finding cures or solutions. They both welcome and help to enforce such controls. The impact of these controls on individuals can be painful but we must maintain a balanced perspective in the world of Sophie's Choice. Not a simple thing to be sure. Judith Swift Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 19, 2011 Report Share Posted January 19, 2011 re: What do you tell the dying patient who has tryed everything with out success? Is " Go home and die " appropreate for you? Cause its not for me. There is no sadder circumstance, I don't have to tell you, and I come upon it too often. My advice is to seek consult with an expert in your disease indication and to inquire specifically about trials or off-protcol therapies that might be tried. (off-protocol therapies can include standard, off-label or investigational agents) The expert (unlike most general oncologists and patients) will be aware which protocol has a realistic potential to help and can be safely administered, having first-hand knowledge of your clinical circumstance (liver, kidney, bone marrow function) and will have knowledge about the Expanded Access program if it needed and how to make use of it. re: When the only upcoming event is death, do I really care about possibilities of toxicity? You want to choose the most appropriate therapy with a realistic chance to help, .... the toxcity can be a dose limiting factor, so I would inquire about targeted agents that appear to be less toxic. As noted earlier, most cancer drugs are not like antibiotics - where if one doesn't work you can try another. Each can narrow the range of available options signficantly - and this is one reason that it's important to test each to see if they provide clinical benefit. The alternative would be a flood of dangerous drugs on the market, with salespitch replacing evidence. I would ask you to consider refocusing your passion to assist in helping to advance the routine and informed consideration of clinical trials. (And there are many obstacles to this goal.) I can see no other way to accelerate progress, and to also sometimes help patients now. Hope this helps. All the best, Karl > > If nothing else, allow me.... the dying patient, the chance to have my > death mean something by giving me a shot at early research with no liability to > the research team. > > Guinea Pig?? Of course...just as if I were in a phase I Clinical trial > although with risks many times larger against me. At least my death now has a > bit more value than just my life accomplishments. Or better said, one last > accomplishment for those who follow while still providing a tiny tiny ray of > hope. > My body, my choice!! > > And while it will take creativity to do it right, it can be done and what I > would give to see an FDA that at least tries to make that happen. > HINT HINT Hint..... When you get there, the black market, last ditch > treatments in Mexico or else where will dissappear. Those people will be > properly served by their fellow citizens at the FDA. > > Givepatientsafightingchance.com may not be the answer, but it does express > ideas of how it could happen. > > Awaiting your answer Karl. > Respectfully, > Leo > > > > > ____________________________________ > From: karls@... > Reply-to: > > Sent: 1/10/2011 6:55:30 A.M. Pacific Standard Time > Subj: Re: FDA > > > > > > First, it is not true that FDA requires superiority to another drug - that > a safer but otherwise equivalent drug could not win approval. (I have > already posted the regulations to support my opinion including a paper that > shows examples. An obvious benefit for such a drug: it would be available to > more patients because of its more favorable toxicity profile. > > Second, ACA (Affordable Care Act) has a provision for encouraging > comparative effectiveness research, but the basis for comparisions - is on > effectiveness, NOT costs. Which. btw. is needed to guide medical decision making - > is good for patients. Lack of such information leading to trial and error > prescribing - and often much unproductive toxicity. > > Regarding FDA evaluation of drugs, the Critical Path document shows that > the rate-limiting factor is the conduct of clinical trials (including > enrollment). The review time - following submission of the data to FDA and its > decision occurs in 7 to 14 months. The document cites also the main reason > for application failures: most new drugs are too toxic at active doses. (Net > harm.) > > Regarding the Abigail Alliance petition: We need to be mindful that drug > safety cannot be determined independent of efficacy. All drugs have > toxicities (even aspirin), particularly cancer drugs, thus phase I cancer studies > (which every expert knows cannot find for efficacy) cannot demonstrate > safety if defined as benefits outweigh toxicities. You may recall how many phase > I studies report: the toxicities were acceptable at the active dose -- > meaning acceptable relative to other cancer drugs and so additional > investigation is acceptable but certainly not approval ... and if approved based on > this level of evidence (as Abigail promotes) would lead to hundreds of such > drugs on the market - and doctors with the burden of having to report and > test for toxicities as is is done in phase II. Which would lead to law suits > against the companies when things went wrong. Which would never be covered > by insurance companies ... etc. In short, a terrible idea. > > Lastly, don't overestimate the meaning of " response " in media reports on > new drugs. Response does not mean benefit necessarily. Lots are drugs can > produce responses but a minority do so while also helping patients to live > better or longer. > > Karl > > > > > > There is a tendency evidenced in government to control what happens to > paying for drugs, especially cancer drugs. > > > > There is a new effort by the head of Medicare ( Berwick) to limit > coverage for cancer drugs. This is similar to the UK's 'NICE' which stands > for National Institute for Clinical Excellence. It's charged with denying > coverage for drugs based on expense. > > > > New drugs are often very expensive. Drug companies want to recoup the > $800 million it takes to approve a drug, and they want to make as much money > as they can while they hold the patent. > > > > The government wants to restrict coverage, to spare costs. > > > > This will be the overriding consideration from now on. > > > > If CAL-101 and other drugs fall by the wayside, that's just too bad. > > > > We Americans have been spoiled by a hands-off policy of drug approval. > That's all changed now. > > > > Unless a drug is specifically approved for a disease, it might not be > paid for. Off-label use may be going away for good. > > > > > > > > > > Sat Jan 1, 2011 11:16 am (PST) > > > > > > The problem is much more complicated than this. The FDA approvals are > based primarily on not just benefit. The two criteria used are: > > > > 1)greater benefit than the currently approved therapies (requires head > to head comparisons) > > > > 2)unmet medical need (nothing approved to compare with) > > > > > > > > The FDA has suggested that it will not allow any drugs to be further > approved for CLL using the unmet medical need criteria. This is how > alemtuzumab and ofatumumab have gained approval. Thus, a trial of drug X in patients > who have disease that is refractory to fludarabine, bendamustine, > alemtuzumab, and ofatumumab will not lead to approval. Even if this agent (like > PCI-32765 or CAL-101) has a 90% rate of clinical benefit / response. > > > > > > > > Likewise, for some very unexplicable reason, the FDA will not allow > multiple drugs to be approved at the same indication. There are 25 different > anti-hypertensives and 10 different cholesterol lowering agents. They did not > have to prove themselves better than the currently available therapies. > Just that they were efficacious. Why not the same thing for oncology drugs? > > > > > > > > Why can we not just show CAL-101 benefit patients and get it approved? > > > > > > > > Additionally, the FDA will not approve an agent that is equally > effective, but less toxic over the current standard of care. This would require a > large study secondary to statistical reasons, but once done, would be a much > easier means to approve these new agents. > > > > > > > > These are just two of the glaring issues where the FDA does not function > in a manner that is in patients' best interests. People have been > complaining or criticizing the pharmaceutical companies, physicians, etc., but all > anyone wants is to get excellent agents to the market as quickly and safely > as possible. A less burdensome system would also encourage more novel drug > development. It could be a simple as once a drug shows efficacy and > safety, that there be programs to allow physicians to use these agents in all > patients while closely monitoring further data on safey and efficacy. Would it > not be great if anyone who needed CAL-101 or PCI-32765 could get it from > their local oncologist? > > > > > > > > I think this is a good opportunity to build a grassroots effort to > change the way the FDA makes these decisions. Let us propose starting a campaign > to address these inadequacies in drug development. This is something that > CIG is very well situated to spearhead. Let me know your thoughts! > > > > > > > > Rick Furman, MD > > > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 28, 2011 Report Share Posted January 28, 2011 Given that I am fairly new to this site I would like to know if and what people have been doing or writing to their Representatives to bring more attention to this topic. If someone has a sample of their letter, I would very much like to see it so that I can work from it and send something to the appropriate person(s) myself. I know that if I get a response(s) from someone, it may not be important for others, so if it seems more advantageous, you could just write me directly and not clutter up the site. THANKS in advance and hope to hear from at least one of you about what I can do. Helen Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.