About ten years ago, somebody published a small case series, suggesting the possibility that BeStaturan might be effective for lupus kidney disease. Although it was a modest contribution in an obscure medical journal, it was noticed by my friend Martha Schwab, a Brooklyn rheumatologist who had devoted her early career to taking care of impoverished, critically ill lupus patients, published a lot of papers about the worst of these cases, and in due course became famous.
Like me, Martha likes to look at men. Unlike me, I think she really believes they are just museum pieces, and as far as I know, she has never actually touched one. However, of the two of us, she may be the smarter one. More on that another time.
Here is one way that Martha is unequivocally smart. She knows how to get right to the heart of any matter. The heart of the problem with lupus kidney disease at that time was that the standard of care (chemo) was unacceptably toxic. And also, if the patient was over 25, there was a high risk it would make her sterile. BeStaturan, if effective, was bound to be less damaging.
Martha wrote a grant application to fund a study of BeStaturan compared to chemo for lupus “nephritis” or kidney disease. She sent it out to fourteen different funding agencies with a clear-minded goal. She did not think BeStaturan was going to be any more effective than chemo, she was just hoping to prove that it was about as good and a lot less toxic.
Knowing what the question is should always be a critical step in interpreting the answer.
In those days, there were not a whole lot of clinical trials going on for lupus and this grant was rejected by thirteen expert lupus review panels for reasons such as: lupus patients are too sick to do clinical trials, lupus patients might not be compliant with the protocol, there might be side effects, the application was too limited and should include all lupus patients, whether or not they had nephritis..... or the application was too ambitious and should only include one subtype of nephritis.....you get the picture.
Back then, people were so scared to do any studies for lupus, in case they might cause some harm to these vulnerable patients, that it seemed perfectly acceptable to wait another fifty years with no new treatments for this chronic, disabling, and sometimes life threatening disease.
Then the last rejection came in, and here is another way that Martha is very smart. Or something. She reads every word in every rejection letter extremely carefully and nothing in the fine print escapes her.
You want to let Martha down gently? Do so at your own risk. Her brain is computing every ameliorating word that comes out of your mouth, and she will twist your subtle nuances into a rope and have you hog tied before you can blink. This last rejection was from the FDA clinical grants program, a tiny operation in Bethesda that was set up by something called the Orphan Drug Act, which funds clinical trials for treatments for ORPHAN DISEASES, defined as having too few patients to interest pharmaceutical developers. This agency picks up very few projects every decade and would have been the last on anybody’s list of likely avenues for support.
They regretfully informed Martha that since there are more than 200,000 patients with lupus in the United States, and since their funds are restricted to orphan conditions, they would be unable to fund her application. But they did want her to know that her proposal was otherwise an important and scientifically sound proposal which they would have been excited to fund.
Martha immediately wrote them back and corrected them that the application was not for all of lupus, it was for lupus nephritis, a condition with less than 200,000 patients in the United States. And, she assured them, she shared their excitement about funding her proposal under these circumstances.
Have you picked up on the FDA’s fatal mistake? They used the word “condition.” If they had used the word “disease” then Martha would not have had the edge. Lupus is a disease, but lupus nephritis is not a disease, it is just a subgroup of people with lupus who have kidney involvement. So lupus nephritis could not be called an orphan disease, which was the definition of the range of illness this division of the NIH was originally set up to serve. But nephritis is a condition. And, with less than 200,000 patients in the United States it would therefore have to be, by definition, an orphan condition.
I am not even sure there was a such thing as an "orphan condition" before the FDA wrote that letter to Martha. But there is now. Google it.
The object lesson here is that no one except Martha would have instantly recognized that loophole and turned it around on the FDA like a boomerang. She got the grant.
You may be wondering what this has to do with romantic advice. Perhaps you have not been reading my previous blogs. Everything has to do with romantic advice. Of course poor Martha is so obsessive compulsive that she will probably never get a date in the first place, but can you imagine what would happen if some poor guy was able to get past her inspection of his nasal cavity, ask her out, let one thing lead to another, and eventually try to break up with a woman of her skills? They would be married in a month.
So if you aspire to be like Martha and apply her life skills to your next rejection all you have to do is listen carefully to every word your darling son of a bitch says, trip him up on his own slippery social lubricants, and then hang on to his bumper with your teeth for a long bumpy drag along the highway to the next town.
I have certainly never denigrated myself in this way, but then again, I live with cats. So who knows? It might work.
Eventually the BeStaturan trial was completed successfully (several of my patients participated in it)and BeStaturan was proven to work at least as well as chemo for lupus nephritis. And, as we all expected, with fewer side effects. Within a few years other studies were done which confirmed these results.
Did the FDA approve it? No, of course not. I was not kidding when I said there has been no new treatment approved for lupus in over 50 years.
Here comes the catch 22 of long-neglected diseases like lupus.
The FDA has a policy that it cannot approve treatments that are only as good as some other treatment....unless that other treatment is already itself approved by the FDA.
However almost nothing is approved for lupus, including the kind of chemo that is effective enough for nephritis.
Bear with me, please. If a treatment is not approved for lupus it is assumed to be no different than "placebo" or dummy pills, even if it happens to be a chemo that it is already known to cure cancer, make you go bald, keep you nauseous for a week, and leave you sterile. Even if it has been the accepted standard of care for lupus for more than twenty years. In the eyes of the FDA, if you give that unapproved chemo to a lupus patient with nephritis it is the same as giving them placebo.
In the eyes of lupus docs, if you don't give something as strong as that unapproved chemo to a lupus patient you will kill them.
So you can't do a study with real placebo, you have to use at least the standard of care. Which is not approved. Which makes the FDA think you are not giving them anything, even though if you are really giving them CHEMOTHERAPY.
If BeStaturan had been more effective than chemo it could have been approved. But since it was only equal to chemo, that was interpreted as being equal to placebo in the eyes of the FDA. And the fact that it was only equal in efficacy but much safer was not good enough. To the FDA, being safer than placebo does not have any value, even if the placebo is the current standard of care and makes you nauseous and bald and sterile.
Believe me I know that Martha pointed out how ridiculous this is to the FDA on more than one occasion. But not even Martha can save lupus from the dodges and subversions of stangulated government beaurocrats(and don't get me started on the rest of the healthcare system)
What did the rheumatologists of the world do then? They started prescribing BeSaturan without FDA approval. BeStaturan rapidly became the treatment of choice for lupus nephritis around the world.
Martha had singlehandedly caused a sea change in the treatment of lupus patients and now she was more famous than ever. She was invited to tour the United States and she went. She was invited to tour Europe, and she went Business Class. Then she was invited to tour China, but unfortunately her nephew was getting married, so she suggested that I go on the tour for her, and sent me her slides.
So that is how I got to Shanghai. Why I was wearing my six inch heels, and how I found myself alone in a scary neighborhood being jostled and poked by a crowd of starving beggars, and in what way this illustrates some of the most important romantic advice I have to give you will be addressed in tomorrow’s column.
Della
Wicked Witch of the Midwest
a woman in her very very late 50's who lives with cats and knows nothing of love
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