Wednesday, November 21, 2007
"The reprogrammed skin cells, by contrast, appear to hold the same properties as embryonic stem cells" according the New York Times.
Presumably, that also includes the ability to grow into a full-fledged human being, if implanted into the proper medium (uterus). Yet theologists such as Richard Doerflinger hailed this advance as the solution to the moral quagmire of embryonic stem cell extraction, which now may not require destruction of an embryo, anyway.
Why is the reformulated skin cell OK to use? If its identical to the stem cell that became my fetus 39 years ago, what makes it OK to experiment on now? Put another way, if I have embryonic stem cell "A" in my left hand, and a re-formulated skin cell "B" in my right, with either having the potential to grow into a human, what makes the one in my left hand holy?
Is it intent? The cell on my left was created by a process of fertilization that was designed to create a new person. Does some kind of "fit-for-purpose" spiritual calculation imbue that cell with a soul upon the biological union of sperm and egg? That immediately makes me think of the 75% of all embryos and fetuses that are naturally disposed of, never destined to develop because of a defect, or because the host mother is unable to house them. They were created with the same intent.
I'm sure Catholicism has an answer for that question, since it's not new, and that's actually something I admire about Catholic scholarship, from Augustine onward - the attempt to use rationality and logic to define spiritual boundaries. Its the convoluted results of that scholarship that leaves Catholics open to scorn from other Christian sects, but at least they try.
Sunday, September 30, 2007
I talked about the probably medication errors that brought her to the hospital. Now, we used a different medication to help end her life.
I was called to the hospital by my three siblings, who had been there a while. They wanted to increase her morphine drip, knowing that the increase would likely be the end of her already labored respiration. But they waited for me to arrive first. When I got there, she was on her side, and each breath made her face look like a fish gasping fon land. Her eyes were open, but not seeing. There was no one else in the room. Since my sister is a nurse in that hospital, she could control the rate of the iv drip.
I was rather alarmed. I wanted to better understand what was happening. I know that my sister wanted Mom to be out of pain, but were we killing her?
I spoke up, and asked that question. Everyone was distressed, but we could still have a conversation about what was going on. My sister asked me what I wanted to do, which was difficult to answer. She wasn't being flippant - there she was, in possession of much greater knowledge about the situation than I could hope to have, but she really wanted my opinion. I asked, what was she really dying from - would she be dying anyway, and were we just hastening a process with the morphine, while sparing her pain. She was bleeding internally, and there was no way to access the bleed without invasive surgery, which we had declined to do, since she would not survive the procedure with her co-morbidities.
Sister went ahead and increased the morphine, and within a few minutes, the very loud labored breathing quieted down. Her eyes remained open. I positioned myself seated by her head, my nurse sister to my left. She was talking to Mom constantly, giving reassuring statements which were likely not heard. My other sister and brother were on the other side. Over the course of several minutes, her respiration continued to drop, as well as her heartbeat. Sister mentioned that when her heart rate dripped below 60, her pacemaker would attempt to kick in. It did, creating a short spike on the monitor, but it didn't last. Her vitals continued to drop quickly from there, and then she just stopped all motion. Her eyes remained open, and the rest of the time we were in the room, and we said goodbye, I considered closing her eyes, but did not.
One bizarre moment was yet to occur. We had to get the attending ICU physician to declare her death, so we called the floor nurses to get the doc. It was about 2 am. I watched him stumble toward the room, he walked in, banging his shoulder on the partly open glass door, walked past the four of us, peered over her, turned around and said "well, she's at peace" to nobody in particular. He stumbled out, banging his other shoulder on the same door. No acknowledgement of any of us. Nothing like "Hi, I'm doctor whoever, I'm sorry for your loss.
JMK (nee H) 1928-2007
Tuesday, September 25, 2007
We'll be jumping into it headfirst, looking for postings for one of our asthma products. Google and Technorati keyword searches, board tracker software, etc.
An anonymous screen name is not enough to warrant action normally for an adverse event report. That's just not a valid, identifiable patient or reporter. But we've made exceptions in the past if the poster describes a serious adverse event that we have a particular interest in for that product.
I'm a little unsure about the value add for this kind of activity. Last Spring, our pro-active monitoring of Cafe Pharma revealed a very embarrassing post by a named individual in our sales force, that compared physician visits by sales reps to grabbing money from a cookie jar. It still made it to Peter Rost's blog, but we did fast damage control by being aware of it that much sooner. Pharma Blogosphere has information about posing as consumers on blogs, but we've never reached that point, and I doubt we will, considering the scowling glances that our legal folks brought to the table, simply at the mention of monitoring sites.
Recent experience is very interesting. For another, more controversial product, we uncovered artificial blogging activity that was an attempt to create business for law firms. One poster would write "I started taking this medicine, and this terrible thing happened!" and the response would be "That happened to me too! I just got a $100,000 settlement for it though. Check it out!" and the whole thing was an elaborate fake. There would be a banner at the bottom for Dewey, Screwum and Howe law offices. We managed to take action, but my readers will be aware that we were (and still are) awash in legal cases.
Speaking of which, I just participated in a review of a regulatory document for a legally challenged product that was hardly a joy to read, as it was all about patient deaths. As I alluded to in a previous post, there are concerns that the legal case overload will throw off our ability to detect genuine safety signals. If our spontaneous caseload normally equals x% of the background "noise" for a condition or event, but the case load for one particular issue skyrockets and clogs our database, our statistical analysis must be reconfigured to handle that, or else a separate analysis is undertaken to discount those legal cases. The latter is what we've actually done. So for this document, the discussion of legal cases was made separate from the rest.
A special shout-out to those of you who let me know you've added my blog to your Google Reader accounts. Let me know if you got this.
Friday, July 27, 2007
has been affected by medications is not a new topic. I've mentioned personal issues with my wife's medications, for example. Now the subject is PB's mother, the likely victim of a medication error.
Mom was rehabbing a severe hip problem, when the staff at the residential rehab place gave her an injectable anti-coagulant (not heparin - the name escapes me. Long day.) apparently without discontinuing her Coumadin. They also gave it IM instead of in the gut, where it's indicated. A hemorrhage ensued, accompanied by the usual complications of low hemoglobin, hypoxia, etc. A hospital acquired pneumonia followed.
The hemorrhage was stopped, and Mom recently returned to a different rehab place, to resume treating the underlying mobility problem. I might add that she has unbelievable insurance coverage, thanks to Dad's employment at another Big Pharma company, which ended in 1983. She pays the first $500 out of pocket for anything - docs, meds, whatever, and nothing else after. Not a dime. Can anybody beat that? I can't.
Since being in the new place for a few days, Mom has been "out of it" - glassy eyed, can't find the right words while speaking, and memory loss. This was a very sharp 79 year old woman who was taking college classes last Fall. There are a few different possible reasons for this - her hemorrhage trauma and associated blood problems may have caused some damage to her brain, she has had poor blood oxygen off and on, and her pneumonia continues, but you wouldn't know it without an x-ray. PB also found out about another possible cause - she started Zoloft at about the same time. I need to research possible adverse effects of that SSRI.
Anyway, what drove me to post all this was the reaction I had today from a visit with her.
People visit their elderly parents for a variety of reasons. They are dutiful, the visits are good for the patients, etc. I have a 96 year old in-law who is visited regularly, which is wonderful, but it's not for the sparkling conversation. PB visits Mom because she is an intelligent and interesting conversationalist. Today was very different. It felt like the dutiful visit from the son with all the conversation in one direction, while she stared into the middle distance, smiled and nodded, with no other reply. This was disturbing enough, but when I spoke to staff members about this, they seemed all too eager to dismiss it with simple explanations. It's the meds, or the PT has her tired. Sounds fine, but it's BS. She's been on meds harder than anything you can buy on the street, and was never like this. She's had terrible arthritis for over 30 years which has worn out her body, and was never like this. She wasn't like this two weeks ago. But the staff doesn't know any of that, and frankly, everyone else whom they care for on this floor is in much the same zombie state. So why should they be concerned about the mental condition of a woman they don't know anything about?
As I sat with her during lunch today, I looked around at the 20 or so other residents, and it occurred to me how odd it is that so many people, with nothing else in common besides their age and infirmity, could act so completely identical to each other. What I'm saying is that every one of these people had some kind of personality at one time - there were former jocks, geeks, princesses, whatever, sitting in that room today, and if you subtracted 60 or so years from all of them, that would have been evident. But today they are all identical, with the same stare, no conversation, nothing at all to differentiate them except the color of their clothes.
I've been in a place populated by people in a worse state, who are experiencing dementia, and I noticed that an old personality re-emerges sometimes in that stage. Bullying, crying, and other highly emotional states come flying back to these folks when their minds lose a grip on reality.
But today, my mother was one of the starers, and it scared me to death. This is not who she is. I'm not ready to lose her mind, or to visit her out of a sense of duty. This sounds terribly crass of me, I know. If her brain was indeed damaged, than there may be no recourse. But when she did speak to me, there was fear in her glassy eyes too, because she know exactly what she's lost. She knows she wasn't like this a couple of weeks ago, and she doesn't know if she'll ever get her mind back.
A shout-out to my brother and sisters who live much closer to Mom than I, and have been such excellent advocates for her, especially A____. She's a nurse who is making sure the staff and the doctors know that something is terribly wrong with our mother's mental state, that this is NOT normal, and needs to be investigated, not explained away. I apologize heartily for every time I ever called you a bitch, dear sister.
Sunday, March 25, 2007
Sound like anyone we know?
It is not true that businesses, as a matter of principle, want to fend off government regulation. Businesses have a metabolic urge to make money, which is as it should be. But when a compliant government gives them the opportunity to use government regulations to enhance their moneymaking, that metabolic urge will overpower any principles about the virtues of free (from government intervention) enterprise.
BTW, note the link on the right from the page above for the Pat Sajak columns. Did you know Pat was a columnist? PB is having an enlightening weekend.
Saturday, March 17, 2007
Friday, March 16, 2007
Anyway, the big legal issue with licensing for us has to do with reporting timelines, and the EU. Volume 9A, the European Commission's guidance document on pharmacovigilance (PV) was published in late January, and the big hit in licensing has to do with individual case handling reports (ICHRs). Specifically, the guidance explicitly states in Part 1, section 4.2, that the reporting clock date is set at "0" whenever the Marketing Authorisation Holder company or any company with a contractual arrangement with the MAH gets information about a adverse event. Ouch. Up until now, our practice has been to consider Day "0" the day when our company gets the report from our licensing partner. The deadline is day 15 - these are calendar days, not working days. So now we have to factor in much shorter data exchange timelines with other companies, and re-negotiate existing agreements.
Unfortunately, we don't have any electronic data exchange with our licensing partners. Our ability to do this is hampered by a lack of shared/compatible data standards and systems, and strained IT budgets. We're faxing and e-mailing case reports back and forth. We're doing this after the case has been entered into our own system, with our own internal timelines. Those internal guideline are geared toward our own company getting the reports in by day 15, not worrying about another company needing to do the same thing. Really, it's substantially shorter than 15 days already, because we've got to make the reports available to our marketing companies around the world, so they can submit the reports (usually a CIOMS) to their regulators.
So now, we have to decide either 1. Rework our individual case handling procedures to shorten our internal timelines, and expect our licensing partners to do the same, or 2. Assign one or the other of the companies to handle all of the reporting duties of a co-marketed drug to all of the regulators around the world, or 3. Share all source materials about adverse events with our partners the day they are received, and trust each party to send reports to their respective parts of the world's regulators
In reverse order, Number 3 is a non-starter, because our two companies could have completely different opinions on a case, if it's regulatory serious, listed with our core data sheet, etc. Then we would have two versions of the same case submitted to agencies, which would be a legal nightmare. We'd also never be able to produce a PSUR with competing cases.
Number 2 above can work fine if we're dealing with another large Pharma with established international reporting. They can do the case handling, submit the IPARs and QLLs to the Europeans for us, etc. The company I'm visiting next week can most likely do all that. But it gets really ugly when you've done a licensing deal with a company that only covers one country, like the US. If your licensing partner in the US is only selling your drug here, they have no reason to submit anything to European regulators. They may not even have the means to do so. And they probably won't tighten their internal timelines to get ICHRs to us quickly, so that we can.
So, we're often stuck with option 1, which is chaos and scrambling, or making exceptions for this or that product received from this or that source. Forget harmonization of processes. Or, my personal favorite variation on option 1, streamline your processes to cut out review times of ICHRs. Just type the case in and send it. This would put our reviewing physicians in a snit, but too bad. My company has too many reviews on an ICHR anyway. We've done some recent benchmarking, finding that other companies are just sending the reports, and worrying about medical review later.
But we know that *others* (Dr Wolfe, big law firms, David Graham at FDA) are scrutinizing our ICHRs, and our goal is to get the MedWatch exactly accurate before they go out the door the first time, being very careful with our wording. Franky, if you read my last couple of posts, it doesn't seem to be making any difference. We're under siege as it is, regardless of what we submit.
Sunday, March 11, 2007
Well, we're happy to say we've conned ever more people into thinking we're doing a good job at work, and we're looking at a promotion within the next few months. There's cutbacks in other parts of the company, so that means that additional justifications have to be made for promotions, new hiring, etc. Really, that means that delays are built into the process, so we don't look so callous to managers who have to let people go. The company can say with some plausible deniability that they are not blatantly ignoring the company's bottom line by promoting PB when others elsewhere are being shown the door.
So, why are some people out the door? Over capacity created by incorrect forecasts, which were made incorrect by some high-profile late stage trial failures. Big ones. A shame - those were the products that actually made us proud to be in this business. They were innovative science, new approaches to unmet needs, etc. They just didn't work, was all. Details, details....
The reports for this particular product have been rolling in for about a year. We've got about 8000 total legal reports with named patients. If you've read Grisham's The King of Torts, then you have some idea about how this works. Now I'm seeing it from the other side.
If you Google the brand name of this product, about 3 or 4 of the top 2o hits are for law firms, but almost all of the Sponsored links are for lawyers. It's also under investigation by Pennsylvania for off-label marketing. This is a huge franchise, and we're counting on line extensions to keep sales up for at least 10 more years. It's a shame that a product becomes more well known for the negative news it generrates than any actual good it has done for patients.
We have little advance warning about when to expect discs arriving from a law firm with hundreds or more cases, but we haven't had to cry uncle yet. Still, the resource drain is huge.