Category Archives: Tysabri

MS Medications, MS outcomes, MS progression, MS research, MS symptom progression, MS treatment, Multiple Sclerosis, Tysabri, Uncategorized

Change Control

PML risk shown in a scatter plot.
PML risk shown in a scatter plot.

It is funny how studying a subject can alter how you think about problem identification and solving. For example, I studied economics in college, and I evaluate many situations and choices from an opportunity cost perspective. If I do this, what am I not able to do? Now I am a project manager, and I routinely look for setting up decision points and metrics by which I will decide whether or not to change and how to change. I look at the strongest part of my management style is a clear but agile change control process.

So when I get involved in a project, the nice part is the defined end-point possibly with decision points along the way. If it is a well planned project, I have various decision points preplanned. Then it is just a question of gathering the information to make the best choice possible. Thinking like this is what started me taking Tysabri.

When I started taking Tysabri, I was flaring frequently and had just been in the hospital for problems swallowing. People who know me are probably sick of the “losing 13 pounds in 6 days when no on Biggest Loser” line. I was having at least two flares a year, and the last one had been on my brain stem. I couldn’t exercise much, and I was miserable. Talking with J, we decided, “Give me five good years over thirty crappy ones.” Over the years, I regained enough balance to run and exercise. I felt more healthy or at least able to fake it well enough to surprise people when they heard I had MS. After five relatively stable years, J and I said the “Give me five good years over thirty crappy ones” mantra still applies.

Now, after eight years on Tysabri, I am back to looking at other treatments. Why? It is not because I am notably flaring. In fact, my progression of symptoms has slowed down to what I always thought aging would be like albeit slightly faster. For that matter, I plan on running a half marathon at Yellowstone this summer.

A couple of years after I started taking Tysabri, a test came out to see if patients have been exposed to the JC virus. Over half of us have been, but for those who have not there is no significant risk of getting the brain infection PML which is the biggest risk factor for those taking Tysabri. I did not want the test because the risk of getting PML, even if positive, was one I was willing to take. Eventually, it was mandated that I take the test so they could track people taking the drug to better understand and quantify the risks. I was positive, but that did not matter in terms of deciding to stay on Tysabri.

Progress is a marvelous thing. As the years have passed, they have refined the test to look at how many antibodies are present. With that information, they are able to assign different categories for the likelihood a patient will develop PML. I have always been OK, as my odds have never gotten worse than my admittedly arbitrary threshold of 1 in 200. That is the mortality rate of chemo recommended to treat the most treatable cancers (recommended if going solely on mortality charts).

However, when looked at over time, my readings are a bit concerning. In July 2014, my reading was 1.10. In three successive tests since then, my count has increased in each to 1.41 in March 2016. Now the accuracy of the tests is something I question, but I admit that is my bias from looking at government stats for a living. I believe everything after the decimal point is suspect. However, each of the successive readings has been higher than the last reading and the trend of multiple readings is something I have a harder time ignoring. This sent me back to look at MS Research Blog for the most recent data I can find.

A few things leap out at me as I review the data. The first is the data only accounts for patients who have taken Tysabri for up to 72 months (6 years). The odds get worse with time on Tysabri, so it seems likely my odds for getting PML are worse than the stated odds for people in my titre tier. The second concern is the big jump in risk between 1.3 and 1.5. Given the risk categories get worse with each titre tier, it seems likely there is no magic number where 1.4999999 is fine, but 1.50 is much riskier. Does my risk really go from 1 in 769 to 1 in 118 with just a tiny bit higher reading (leaving off my questioning the accuracy)? I suspect it follows the trend line between each of the tiers.

Given my time on Tysabri and my reading, I suspect I am nearing my 1 in 200 threshold. However, I feel OK. I like to think of myself making logic based decisions, and I tend to think these decisions are best made before emotion enters. For example, when I buy a stock, I do so only when I can identify selling points high and low. At the high or low point, I have a decision to make on keeping or selling based on what I think my options are at the time with a bias towards getting out. It always seems important to me to set expectations and recognize when they have been met to a “good enough” extent.

The 1 in 200 is supposed to be my decision point with a bias towards getting out based on how my odds are trending. It is just hard to make decisions based on odds when the decision likely involves worsening conditions… they are just less worse than a likely alternative. So pardon me while I take a few months to enjoy the relative calm in my MS, to be thankful for the 8 years of comparatively good health, to research my next steps, and to run because I still can. Deciding to change need not always be instant, and maybe the time to change is what I buy myself by deciding now. That is the point of a change control process, to have in place a set time to change and a method for determining how to change.

However, change control does not make the change and contemplating what it portends easier.

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brain training, MS medication, risk management, teaching kids how to think, Tysabri, Uncategorized

“One, Two, Many, Lots, and Whole Bunches!” – Life in a Base 100 World

I have always been told we use a base ten numbering system. I maintain we are a base ten times ten when it comes to absorbing the meaning of numbers.
I have always been told we use a base ten numbering system. I maintain we are a base ten times ten when it comes to absorbing the meaning of numbers.

There seems to be a logical disconnect in our brains when it comes to very large numbers. We have ten fingers and ten toes. We are fine counting to ten. When it comes to counting to 100, we don’t have big problem either. However, I note that I can put myself to sleep counting down from 100 by “1’s” or “2.5’s.” One hundred seems a natural barrier, and because we are a tens based society, ten times our natural barrier is still comprehendible. However, as we go further from hundreds our understanding of scale diminishes. When we start counting in thousands, we may as well go back to the childhood counting, saying “One, two, many, lots, and whole bunches!”

We can intellectually go beyond a thousand, but I note that when we do, we group things so that we are counting the groups again, never going beyond the hundreds. For example, 530,253,063 is said “five hundred thiry million, two hundred fifty-three thousand, and sixty-three.” We have kept our counting to the hundreds of a group. That seems a natural cognitive limit of our intuitive understanding.

I think this inability to think beyond hundreds inhibits some of our intuitive understanding of scale. I see this all the time even amongst those of us dealing with numbers all the time. At my work, a group of us play the lottery when the winnings are big enough for all of us to retire. We call it the “stupid people’s tax” because we all know the expected return for our money is nothing and we pay anyway. The odds of one in hundreds of millions feels like one in hundreds with the millions only understood intellectually.

It is with this in mind that I read much of the news about the Syrian refugees. I see reports where countries take in thousands or even tens of thousands, and it feels impressive for some group to advocate increasing the number of refugees from one thousand to ten thousand. It feels like the group advocating for ten thousand is much more heroic. I submit this thinking is at least partially the result of our inability to comprehend the number of refugees is estimated at 10.8 million. Again, we focused on the wrong parts when thinking about the scale of the crisis. Like the examples above, we thought about the numbers I underlined instead of the description after them. It is very hard to get to 10.8 million (number of refugees) when we are dealing with them a thousand to maybe ten thousand at a time. When I think about the true scale of the problem, it feels like the responses are akin to trying to put out California forest fires with one spoon full of water at a time. Some may bring the teaspoon while others bring a ladle, but how effective are either?

Don’t take this wrong, our minds inability to grasp large numbers has advantages. I take a drug that has a chance to cause severe brain infections and possibly kill me. The published odds I get on that happening to me are changing all the time. My neurologist asks at every visit if I am concerned by the odds and want to switch medications. My most recent numbers were one in seven hundred, and I told him again I will be concerned when my odds worsen to below one in two hundred. Above that, my mind treats the risk like the odds of being struck by lightening or dying in a car crash on the way to work. These things happen all the time, but the odds are not worth worrying about because my mind puts them all in the remote risk category. My minds inability to internalize the risk helps me live my day to day life. I justify my thinking about taking Tysabri by noting my odds are still better than a Cancer patient taking Chemo which has a mortality rate of one in two hundred. I do not think about the large number that is my odds of getting the brain infection. Rather I think about it in comparison to something else.

The comparison method is the only way I think most of us truly attach meaning to large numbers. This is what I am doing when I compare the mortality rate taking Tysbari with the mortality rate of a cancer taking chemo. When we release data on the United States economy, most people care more about the direction of the change in numbers and how fast they are changing rather than how big the actual base number was. Most of us really cannot intuit the GDP reports talking about trillions of dollars.

When it comes to large numbers, we just need to be careful to be mindful of what the large numbers are for which we see differences and the differences in scale between different large numbers. If we can manage these two obstacles, we might avoid some of the common mistakes in our perceptions of the universe in which we live. Maybe then we can stop comparing “many” to “whole lots.”

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