Statistical Design: Clinical Development of Drugs and Biologics

A few years ago, my colleague Steven E. Linberg was teaching a course, “Clinical Development of Drugs and Biologics,” at Johns Hopkins University. He asked me to give a guest lecture on statistical design.

The class was once per week, 3 hours, in the evening, so I had plenty of time to explain the topic to the students, who were a group with credentials in drug, device, and biologics development, but who mostly knew little about statistics and certainly not much about the practicalities of applying it in real-world research. So I tried to leave them with an emergency first-aid kit that couldn’t really let them do statistical design on their own, but would help them interact with people who could and to ask the right questions.

To add realism, I used the field of spinal cord injury as an extended example of the way that reality can mess up one’s neat assumptions, managerial goals, and mathematical formulas.

So people more interested spinal cord injury than in drug and biologic development may want to read it too.

Using ASIA Motor Score as outcome in spinal injury

In October ‘06, the people at ICORD (International Collaboration On Repair Discoveries) in Vancouver asked me to give a talk. I spoke on Statistical Considerations in Designing a Trial in Spinal Cord Injury with ASIA Motor Score as the Outcome, and you can download a 1.5 MB pdf copy of my slides. I tend to write everything I plan to say into my slides, so they’re less schematic and easier to read than most.

Recently there have been many potential treatments for spinal cord injury reaching the stage of development where they’re ready for human trials, and thus there’s interest in using previous data to develop design information. The largest existing data set is the one from the Sygen GM-1 multi-center trial, which recruited 760 patients in 28 centers in the US and Canada in the 1990s. I was a designer of it, and so my colleagues and I have been trying to be helpful in filling requests for information.

This talk summarizes my preliminary thoughts about using the ASIA (American Spinal Injury Association) motor score as the outcome variable.

Reduced Bladder and Bowel Control after Severe Spinal Cord Injury — Even in Patients Able to Walk

Regaining unlimited mobility, including the ability to walk, is a main goal for spinal-cord-injured (SCI) patients. Still, more limited accomplishments — such as bladder and bowel control — would significantly improve quality of life for those lacking them. Conferences and publications have cited such endpoints as under-studied.

In the 1990s, Fred Geisler and I were the designers of the Sygen multi-center trial in acute SCI. Later, we collaborated with Kim Anderson, using the data from that trial to investigate the relation between the ability to walk and bowel and bladder control.

We found that bowel and bladder impairment, representing a serious impact on quality of life, affect a very large portion of the SCI population and are a significant problem, separate from ambulation and needing specifically directed work.

You can download a pdf slide presentation showing the details of our results.

More on clinical trial design for beginners

My earlier post Clinical trial design — for beginners has been one of my more popular ones. People who’ve read that and would like to know more, can download

Medicine: Using probabilty to treat people versus using it to treat groups

I saw an interesting post complaining about the “magic” of clinical trials and the refusal by many people to consider other types of evidence rationally. One commenter there replies, “Let me give you an example I like to use. George Burns smoked 4 or 5 cigars every day and lived to be 100. Does that mean smoking cigars is harmless?”

I’d like to offer my 2 cents.

Let’s try a different example first, not George Burns. You go to the airport, planning to fly to Peoria and visit your aged mother. The ticket agent informs you that, statistically, fewer than .01 of the passengers leaving your airport go to Peoria, and therefore Peoria wouldn’t work for you and isn’t really what you want. She takes your money and hands you a ticket to Orlando.

Clinical trial design — for beginners

This post is based on an e–mail series I sent to a friend in industry. He was responsible for overseeing the design of a clinical trial, and he asked me as a professional to tell him in simple words how certain basic statistical ideas work. He’s intelligent and educated, but his own expertise doesn’t happen to be in statistics. Like many such people, he thinks of statistics as an impenetrable black art. As I mentioned, he’s a friend—so I tried to level with him and explain in simple, colloquial language what I wanted him to know. Other people might like to read it. I’ve tried to avoid technical or mathematical prerequisites and to explain as I go along, but it probably would help if you’ve previously heard at least buzz about terms like p–value.