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March 31, 2005
Did Merck decide to "see no evil" in Vioxx?
Developing pharmaceuticals is a tough job. And designing and conducting tests for a drug's safety and efficacy is quite complicated. You must carefully identify the study questions you want to answer, because everything from the type of people you enroll, to the study length, the analysis, and how you interpret the results depends upon a careful framing of the question. With all of these complexities, it's natural to expect some mistakes and missteps. But an excellent article by Robert Burton at Salon.com calls into question whether Merck's failure to recognize deadly heart-related side effects of its pain drug, Vioxx, were simple mistakes or a calculated decision not to directly investigate.
The story, "How Merck stacked the Vioxx deck" lays out how Dr. Burton sees it: that Merck knew there were heart risks with Vioxx but conducted studies "designed to avoid finding out how serious they were."
To check out the article, Salon offers non-members a 'Free Site Pass' that allows you access to their site after watching a short ad from their sponsors. For those of you don't want to bother, no worries, I've excerpted some key parts for you:
Given the enormous intellectual investment in the design of a drug like Vioxx, it is reasonable to presume that all potential outcomes were seriously entertained. I must presume that Merck would factor in what might happen to Vioxx sales with each study result. And so it's hard to escape the sadly cynical conclusion that the company consciously crafted its tests to avoid exposing the risks of Vioxx to the public.
[snip]
As far back as 1984, Garret FitzGerald and his colleagues at the University of Pennsylvania, writing in the New England Journal of Medicine, showed that the COX enzyme might prevent arterial blood clot formation. FitzGerald suggested that this side effect might mean little in healthy persons but could be dangerous to patients with severe atherosclerosis.
[snip]
Merck responded to FitzGerald's research by re-analyzing all of its Vioxx clinical data, and included FitzGerald's potentially worrisome lab data in its FDA application. (This data was published in 1999 in the Journal of Pharmacology and Experimental Therapeutics.) Merck also declared that it had adopted the standard procedure for "facilitating rigorous scientific analysis, on an ongoing basis, of all competing hypotheses about potential CV [cardiovascular, or heart-realted] risks or benefits from Vioxx."
Was this a sufficient evaluation of a potentially serious side effect of Vioxx? Or should more have been done? Given that it is standard practice to assess all serious potential risks of new drugs, FitzGerald's concern should have been directly addressed.
But rather than design a study focused on the C.V. risks of Vioxx, Merck created the VIGOR (Vioxx Gastrointestinal Outcomes Research) study in 2000. It compared the incidence of G.I. complications of Vioxx to naproxen, another conventional NSAID, whose most popular brand is Aleve. The goal was to prove that Vioxx was an equally effective but safer drug than an over-the-counter NSAID. Unfortunately, the study, published in the New England Journal of Medicine, revealed a twofold increase in C.V. risk for patients who took Vioxx. Of course, Merck acted surprised. What Merck didn't tell us is that it had stripped the deck of patients at high risk for heart disease.
Burton goes on to explain that the VIGOR study... (By the way, isn't that a great name for an efficacy trial? I don't need to see the results, I can just tell that Vioxx must work from that great name.) ...sorry, that the VIGOR study's participants were predominantly women, the mean age was 58, and the study duration was a little less than a year. Given that women tend to develop heart disease an average of 10 years later than men, it would be hard to draw conclusions about heart side-effects from this study group over the study time period. Meanwhile, other studies continued to raise questions about the heart risks of COX-2 inhibitor drugs, the class of drugs that includes Vioxx. And Merck looked like it was going to investigate...
According to an article in the New York Times earlier this year, the company planned to initiate a major C.V. risk study called VALOR [another great name!] in 2002. But just days before company researchers were to submit the study's protocol to the FDA, the project was abruptly halted. Merck did not explain why. It issued a general statement, saying that as it was designing the study, "we continued to ask ourselves and our consultants whether this was the right way to definitely answer" the question of whether Vioxx posed C.V. risks. "We ultimately decided not to conduct that particular study."
[snip]
To further distance Merck from any responsibility for those who had recently begun taking Vioxx, Kim added, "While the cause of these results is uncertain at this time, they suggest an increased risk of confirmed CV events beginning after 18 months of continuous therapy."
No, the risk didn't begin after 18 months. This would be analogous to saying that daily sunbathing for 18 months poses no risk for melanoma if no melanomas are detected during that time, and that the risk doesn't begin until the melanomas are first discovered. The risk is present from the beginning but only evident at 18 months.
Finally, Merck is asking us to believe that it didn't suspect from the outset that Vioxx might increase the risk of heart attacks and strokes. It's telling us that its studies were adequately designed to detect both the incidence and possible underlying mechanisms of cardiovascular risks. It wants us to accept that a nine-month study, abruptly concluded, was insufficient evidence for the withdrawal of Vioxx because it was reasonable to presume that naproxen had a cardio-protective effect.
For me, the sad but inescapable conclusion is that Merck made an informed decision to avoid knowing the full extent of Vioxx's potential risks for heart attacks and strokes.
There's lots more good stuff in the story, but I've probably excerpted too much already, so go check it out. At the end of the article, Burton calls for transparency of the data so independent doctors and scientists can review it for themselves. Finally, Burton acknowledges that decisions to take drugs must involve a personal risk-benefit analysis between us and our physicians. But we can't have drug companies playing a shell game with us and revealing only those results it wants us to see.
Posted by rigd0003 at 03:38 PM | Comments (1)
March 28, 2005
Best places to work in fed gov't
One of the largest employers in the public health field is the federal government. Even though, with my current situation, I probably won't be working for the feds anytime soon, it's always good to know what the current fed employees think of their jobs. That's why this site,
The Best Places to Work in the Federal Government, caught my eye.
Brought to you by Partnership for Public Service and the American University's School of Public Affairs, Best Places is a ranking of federal agencies and subagencies by the employees who work there. According to their web site, the rankings "use the opinions of over 100,000 federal employees to rate 28 federal agencies and nearly 200 subagencies in the executive branch."
So who's #1?...NASA. Followed by the National Science Foundation and the Office of Management and Budget.
Here are more results:
• EPA ranks fairly high as 5th overall
• Health and Human Services ranks 11th overall
→ CDC (part of HHS) ranks 68th over all the subagencies
• Department of Agriculture ranks 13th overall
• DoE, Defense Agencies, and FEMA round out the bottom of the list
It should be noted that these rankings were compiled as a way of promoting the federal government as a good place to work and showcasing some of the bright spots. And contrary to what some might think, I don't think showcasing is a hard thing to do for some departments. As I've said before, there are some professions where the best cutting-edge work is done at the federal level, and I think that is reflected in those agencies towards the top. In the same vein, it may be that the agencies with the least cutting-edge, less unique work have come out on the bottom...
Posted by rigd0003 at 04:34 PM | Comments (1)
March 22, 2005
Helping you along your thesis path...
Everyone's path to a Masters or PhD is different. Maybe that's why so many of us feel a bit adrift when it comes to charting our course of progress. There have been lots of books on the subject of thesis writing, but I've always felt too busy to read them. Here, then, are some tools I've found useful to have along for the journey.
A Progress Journal
In the same vein as a lab notebook, keeping a progress journal lets you look back to see what you've done and the reasoning behind the decisions you've made. Here are some of the things I use my journal for:
- Keep a record of all the meetings I've had with my adviser and committee members
- List the tasks or next step we've agreed on and record why those decisions were made
- Keep track of administerial timelines, like all the paperwork I need to file with the Graduate School, when each piece was filed, etc.
- Record ideas and musings that may prove useful in the future
There a lots of journal software out there, many of them with free trial periods (journals at tucows.com, EJournal, the Journal). I use i*write. I like it because every entry is stored by the entry date and the entry category. Plus, I can insert document short-cuts (or entire documents) so I can keep track of all the files that pertain to that particular entry. It also has a good search function.
One-Draft Thesis
John Carlis, a Computer Science & Engineering professor here at the U of M, has written a guide for PhD students and faculty called, "Design: The Key to Writing (and Advising) a One-Draft Thesis." His goal in the guide is to help students develop an effective and efficient way to work. It's an easy read with a lot of good ideas. Check it out at his personal web site (a link to download a PDF of the document is listed under "Selected Papers"). Here are some gems from the guide:
- A thesis is all about your contribution to the field: the novelty, the consequence, and the evidence. This helps you set boundaries on what your thesis will and won't do, and will help you figure out when you're done. Grasping this concept is huge!
- Use paragraph topic sentences to outline your draft, so your adviser knows where you're going and can make changes without lots of re-writing entire pages.
- Designing and writing with a story tree helps you write for your readers' benefit, not for your own.
Dissertation Calculator
The University of Minnesota has designed a Dissertation Calculator. Here's how it's described:
The Dissertation Calculator is a tool that helps demystify the process of completing your dissertation or thesis. The Calculator breaks down the dissertation process into manageable deadlines and provides you with important resources and advice. Using this tool can help you develop your specific process in collaboration with your department, advisor, writing group, and others.
To start, you type in a target date of completion. Then you get a list of stages along with a desired deadline for completing the stage. Each stage has a link that describes why the stage is important, the tasks for that stage, and links to more resources. If you are a U of M student, you can sign up to have reminders sent to you by e-mail.
A Support Network
I get by with a little help from my friends...
- Lennon/McCartney
This is a very important part of dissertation work. In fact, it is a dedicated stage in the aforementioned Dissertation Calculator. There are many ways to seek support and group contributions: a writing group, a regular get-together with your PhD-seeking friends, or attending group support sessions.
Haiku
It's incongruous, I know, but a nice ending to this post.
Milestone
Another milestone
Resting only a moment
Enjoying the view
Copyright 2004, by Joseph Rohrbach
Journey
You cannot get where
You are destined to go without
Leaving where you are
Copyright 2004, by Joseph Rohrbach
Posted by rigd0003 at 04:01 PM | Comments (2)
March 21, 2005
Creating site icons for your blog
I just found out how to create those little icons () that show up next to your URL in Firefox and IE. It's actually quite easy. Here are some resources:
How to create a bookmark icon
Creating a favorites icon (favicon.ico) for your site - favourites, bookmarks icon
Creating favicons with Adobe Photoshop and Adobe GoLive
I used Adobe Photoshop Elements to create mine. It worked pretty well, but I started out with something too complex for the tiny size (16X16 pixels) and had to keep simplifying the image until I was satisfied. Have at it!
Posted by rigd0003 at 11:59 AM | Comments (0)
March 20, 2005
Wonderful, Wonderful København
Okay, this post isn't exactly timely, but I wanted to show pictures from my trip to Copenhagen, Denmark. I was in Copenhagen for a week in mid-January to visit some researchers at the Danish Institute for Food and Veterinary Research. I know what you're thinking, "Denmark in January?!" But this was a paid business trip and my first trip overseas. I was very excited and it turned out to be just like the Danny Kaye song, it was wonderful.
One thing I had trouble adjusting to was the light. It is far enough North to have significantly shorter days in the winter. The sun didn't rise until 8 o'clock and it set about 4:30. But the really disorienting thing about it was that the sun never got that high in the sky. That's why all of my pictures look like they were taken just before sunset. Some of them were, but others were taken in the middle of the day. In fact, because of the short winter days, Denmark has a law governing how much natural light must be accessible to a worker. This means that most office buildings have skylights and individual offices have windows. I didn't see any cubicles while I was there. But here's a bit of what I did see:
Frederiksberg Runddel (Circus) and Frederiksberg Kirke. In the winter, there is skating at the entrance of the summer palace gardens. The Kirke in the background is an octagonal church built by Dutch immigrants in 1734, who were brought in to tend the elaborate royal gardens in the adjacent Frederiksberg Have.
Frederiksberg Slot, the pale yellow Summer Palace that overlooks the Have. Built by Frederik IV in the early 18th century. It sits high atop Valby Bakke hill and in its time offered an uninterrupted view (on the opposite side) of the city ramparts and the Swedish coastline. This side of the palace looks out over the gardens.
Christiansborg Slot, Slotsholmen. Historical heart of Copenhagen and seat of Danish government.
Slotsholmen is actually an island separated from the rest of the city by this canal, the Frederiksholms Kanal. You may be getting the idea that Copenhagen is a city of spires.
The Kastellet, or Citadel, has been occupied since 1660 and is the oldest still-functioning military base in Europe. It is a star-shaped base surrounded by grass-covered bastions and moats. This is one of only two gates into the base.
The Rådhus, or city hall, is an impressive feature of Indre By, the city center. The gold figure in the center is Bishop Absalon, the founder of Copenhagen.
This is Gefion Fountain. As the myth goes, the goddess Gefion was promised as much land as she could plow in a single night. She turned her four sons into oxen and ploughed out a chunk of Sweden and tossed it into the sea, creating the Danish island of Zealand, on which Copenhagen resides.
There are lots more wonderful things about Copenhagen: omnipresent bicycles - even in winter (although there wasn't snow on the ground when I was there), numerous squares, and the ubiquitous English (everyone speaks English, making it a good place for beginning travelers). I would love to go back and tour more of the country some day.
Posted by rigd0003 at 02:01 PM | Comments (0)
March 19, 2005
A Night at the Opry
Some interesting things we learned about the Opry:
- The Opry is a co-op! All performers are co-op members and must perform at least four times a year to retain their membership.
- Opry shows are split into half-hour segments, each with a unique host, sponsor, and 3 - 4 performing groups.
- Saturday nights there are two full shows at the Opry, one from 6:30-9 p.m., and the second from 9:30-midnight. A whole new audience is brought in for the second show.
- We got to see 19 different performers during one show!
- The abbreviation for the Grand Ole Opry is GOO. One of the major sponsors of the Opry is GooGoo Clusters, a Nashville treat. Coincidence? Apparently it is only a coincidence, since the candy's inventor named it for his infant son's first word. But I thought the association was kind of funny.
Posted by rigd0003 at 03:59 PM | Comments (0)
March 16, 2005
Tip o' the hat to the Little Master
 |
Sachin Tendulkar has become the 5th cricket player to score 10,000 career runs today in India's test match against Pakistan. It's no wonder they call him the "Little Master". Did you know that he swings one of the heaviest bats in world cricket? His bat weighs almost 3-½ pounds! And his technique is almost all wrist action -- I don't know how he does it! Incidently, there was a great story in the New York Times on Sunday about what this recent test series means to the Pakistanis and Indians who live in the Punjab Province, which has been divided since the partition in 1947. |
Posted by rigd0003 at 01:00 PM | Comments (0)
March 15, 2005
Computer woes
Wow, what an ordeal! I haven't been posting recently because I've been out of town, but within a day of coming home my computer started greeting me with horrible fatal exception blue error screens when I tried to launch my web browsers and e-mail programs.
This was the classic computer frustration -- it seemingly came out of nowhere. One day it was purring like a kitten, the next day it was hacking up hair balls! All's well now, thanks to spyware finders, system maintenance/optimizer software, and a USB flash drive.
For those who haven't done so, I would highly recommend downloading AdAware and Spybot -- two free spyware "search and destroy" programs. Using both of them together is ideal because one often finds spyware that the other misses. (It does seem a little dumb that anti-virus software does not find spyware, but there you have it.) It's amazing what your computer catches even when you try to be careful. I've been using these programs for a while now, but I always forget to update and run them regularly.
One thing I had never done at all before now was use a system maintenance or optimizing software program. These look for junk files, clean up registries, and help you manage start up programs to keep everything running smoothly and prevent crashes. My laptop is over 5 years old, so you can image what had piled up!
There are lots of options out there (try browsing tucows.com). The only drawback to these programs is many run the scan for free, but the fix will cost you the price of buying it (about $25-$30 for the full-fledged programs). I did happen upon one that has a free 30-day trial period, and it's loaded with lots of clean-up and efficiency options. It's called Ace Utilities - check it out, you've got nothing to lose! So after all of my desparate attempts, imagine my elation when, after a very long day of trying to trouble shoot, I hit the "Repair" button on my newly-purchased maintenance program and it worked! I had my old computer back!
It certainly could have been worse, but a full day of this was stress and frustration enough...
Posted by rigd0003 at 09:48 PM | Comments (1) | TrackBack
March 04, 2005
A model is a set of assumptions
As you might know, my thesis work consists of evaluating current models, then using what I like about them and fixing what I don't like about them to create one of my own. It doesn't matter what sort of models I'm looking at or even what questions I want to answer about them, I'm learning from my adviser and my own experience that they all boil down to the same thing - assumptions.
For the most part, models are just short-hand for how you get from one place to another, from A to B. You start out with certain climate data and you end up with a weather prediction; you start with your personal and financial situation and wind up with an investment strategy; you start with exposure and illness information and wind up with a measure of causal association. The model you use tells the story of how all of these data relate to one another and how they come together to give you the outcome - the answer to your question . This "telling of the story" is just a description of your assumptions: this is a linear relationship, these follow a Normal distribution, this decays at this given rate.
I find I'm having a really hard time excavating assumptions from some of the models I am reviewing. Part of the problem is that modeling is a whole new field for me and I don't have much experience. Another part of it is that I hadn't been trained to identify the assumptions in the models I used through most of my schooling (mostly statistical models). But a large part of my trouble is also that many people are not accustomed to laying out their assumptions in a straight-forward manner.
So the next time someone wants you to use a model - a tool - to do some work for you or solve a problem for you, simply ask, "what are the assumptions this model is making to take me from A to B?" They you can decide for yourself if the path the model is taking is one you can accept. But if they can't answer your question, then you've got a REAL problem.
Posted by rigd0003 at 11:48 AM | Comments (0)
March 03, 2005
Tonight - Rob Corddry reports on "New Forms of Journalism"
I know there's been a lot of talk about Jeff Gannon, but I couldn't resist posting this from Salon.com. Just another example of why "The Daily Show" rocks.
On Monday, a fake reporter infiltrated the press corps at a question-and-answer session in front of New York's City Hall. Disguised in a fake mustache and hair piece in an obvious spoof of discredited White House reporter "Jeff Gannon," the intruder identified himself as "Dino Ironbody." He got City Council Speaker Gifford Miller's attention and asked: "How do you feel about the president's awesome plan to privatize Social Security?"
Miller caught on right away. "I'm not such a big fan of the president's plan to private Social Security," he answered. "I think Social Security has worked pretty well for generations and we outta stick with something that works."
The reporter was Daily Show correspondent Rob Corddry, shooting a segment that will air on Thursday night's show.
Posted by rigd0003 at 04:36 PM | Comments (0)