Tracking adverse events during kidney biopsy

Steve Simon

2007-11-19

Categories: Blog post Tags: Adverse events in clinical trials

This is a major revision of the March 14, 2007 and April 5, 2007 weblog entries. I have been helping a colleague who is interested in monitoring the safety of kidney biopsy events. He was kind enough to let me use his data set on my web pages in order to illustrate some new methods for monitoring adverse events. This data set allows you to see some examples of the use of control charts to track adverse events. Here is the raw data.

2003-01-12 ---- 2003-01-28 ---- 2003-02-01 ---- 2003-02-14 ---- 2003-02-14 ---- 2003-02-15 H-NO 2003-03-09 ---- 2003-03-17 ---- 2003-03-22 ---O 2003-03-25 ---- 2003-03-30 H--- 2003-03-31 ---- 2003-04-05 ---- 2003-04-13 ---- 2003-04-15 --N- 2003-04-19 H-NO 2003-04-22 ---- 2003-04-27 ---- 2003-05-11 ---- 2003-05-12 ---- 2003-05-13 ---- 2003-05-20 ---- 2003-05-24 ---- 2003-06-02 ---- 2003-06-08 ---- 2003-06-10 ---- 2003-06-22 -I-- 2003-06-23 ---- 2003-06-24 ---- 2003-07-04 ---- 2003-07-06 ---- 2003-07-15 ---- 2003-07-22 ---- 2003-07-25 ---- 2003-07-26 ---- 2003-07-26 ---- 2003-08-01 ---O 2003-08-24 ---- 2003-08-26 ---- 2003-08-30 ---- 2003-09-26 ---O 2003-09-26 ---- 2003-09-27 ---- 2003-09-27 H-N- 2003-09-28 ---- 2003-10-10 -I-- 2003-10-10 ---- 2003-10-12 --N- 2003-10-19 -I-- 2003-10-24 ---- 2003-10-24 -I-- 2003-10-26 ---- 2003-10-31 H--- 2003-11-02 ---- 2003-11-07 -I-- 2003-11-07 ---- 2003-11-09 ---- 2003-11-09 ---- 2003-11-15 ---- 2003-11-17 --N- 2003-11-29 -I-- 2003-12-12 ---- 2003-12-20 ---- 2004-01-03 ---- 2004-01-04 ---- 2004-01-23 ---- 2004-01-25 --N- 2004-02-08 ---- 2004-02-10 ---- 2004-02-14 ---- 2004-02-15 ---- 2004-02-15 ---- 2004-02-17 ---- 2004-02-20 ---- 2004-02-22 ---- 2004-03-02 ---- 2004-03-19 -I-- 2004-03-22 ---- 2004-03-26 ---- 2004-03-27 H-NO 2004-03-28 ---- 2004-04-10 ---- 2004-04-18 -I-- 2004-04-25 ---- 2004-04-30 ---- 2004-05-02 ---- 2004-05-11 -I-- 2004-05-22 ---- 2004-05-23 ---- 2004-05-28 ---- 2004-06-08 ---- 2004-06-15 ---- 2004-06-20 -I-- 2004-06-26 ---- 2004-07-05 ---- 2004-07-09 ---- 2004-07-09 ---- 2004-07-11 -I-- 2004-07-13 ---- 2004-07-24 ---- 2004-07-30 ---- 2004-08-01 ---- 2004-08-01 -I-- 2004-08-06 H--- 2004-08-07 --N- 2004-08-10 ---- 2004-08-13 ---- 2004-09-05 ---- 2004-09-12 ---- 2004-09-21 ---- 2004-10-08 ---- 2004-10-12 ---- 2004-10-13 ---- 2004-10-22 ---- 2004-11-02 ---- 2004-11-07 H-NO 2004-11-14 ---- 2004-11-28 -I-- 2004-11-29 ---- 2004-12-07 ---- 2004-12-10 -I-- 2004-12-12 ---- 2004-12-13 ---- 2004-12-26 ---- 2004-12-26 ---- 2005-01-03 ---- 2005-01-03 ---- 2005-01-09 -I-- 2005-01-13 H--- 2005-01-15 ---- 2005-01-17 ---- 2005-01-17 H--- 2005-01-20 ---- 2005-01-25 H--- 2005-01-28 ---- 2005-02-08 ---- 2005-02-11 --N- 2005-02-11 ---- 2005-02-14 ---- 2005-02-18 ---- 2005-02-21 ---- 2005-03-01 ---- 2005-03-07 ---- 2005-03-07 ---- 2005-03-18 ---- 2005-03-18 --N- 2005-03-19 H-NO 2005-03-21 ---- 2005-03-25 ---- 2005-04-10 ---- 2005-04-11 ---- 2005-04-11 ---- 2005-04-15 -I-- 2005-04-23 ---- 2005-04-25 HI-- 2005-04-26 ---- 2005-04-26 ---- 2005-04-29 ---- 2005-05-07 ---- 2005-05-09 ---- 2005-05-13 ---- 2005-05-23 ---- 2005-06-06 ---- 2005-06-06 --N- 2005-06-10 ---- 2005-06-13 ---- 2005-06-19 ---- 2005-06-20 ---- 2005-06-26 ---- 2005-06-30 ---- 2005-07-08 ---- 2005-07-18 ---- 2005-07-22 ---- 2005-07-31 H-NO 2005-08-15 ---- 2005-08-19 ---- 2005-08-21 H-N- 2005-08-22 ---- 2005-08-28 ---- 2005-08-29 ---- 2005-08-29 ---- 2005-09-12 ---- 2005-09-12 ---- 2005-09-16 ---- 2005-09-19 H--O 2005-09-23 H--- 2005-09-24 H--- 2005-09-25 ---- 2005-09-26 ---- 2005-09-30 ---- 2005-10-09 ---- 2005-10-16 ---- 2005-10-21 H--O 2005-11-04 H--- 2005-11-07 ---- 2005-11-14 --N- 2005-11-15 ---- 2005-11-15 ---- 2005-11-26 ---- 2005-11-28 ---- 2005-12-02 ---- 2005-12-12 ---- 2005-12-16 ---- 2005-12-18 ---- 2006-01-01 ---- 2006-01-02 ---- 2006-01-06 --N- 2006-01-16 ---- 2006-01-16 ---- 2006-01-17 ---- 2006-01-20 ---- 2006-01-22 ---- 2006-02-05 ---- 2006-02-06 H--- 2006-02-13 --N- 2006-02-24 ---- 2006-02-26 ---- 2006-03-12 ---- 2006-03-19 ---- 2006-03-20 ---- 2006-03-22 ---- 2006-03-27 --N- 2006-04-03 ---- 2006-04-03 ---- 2006-04-14 ---- 2006-04-17 ---- 2006-04-30 ---- 2006-05-01 ---- 2006-05-07 ---- 2006-05-09 ---- 2006-05-12 ---- 2006-05-12 ---- 2006-05-13 ---- 2006-05-14 ---- 2006-05-19 ---- 2006-05-21 --N- 2006-05-22 --N- 2006-05-26 ---- 2006-05-29 ----

The dates represent dates of the kidney biopsies for 239 consecutive biopsies. I have shifted these dates by an arbitrary constant to protect confidentiality. Those dates with an H represent biopsies where gross hematuria was noted (n=21). An I represents a biopsy where an inadequate amount of tissue was obtained (n=17). An N represents a biopsy where narcotics were required to control the pain (n=22). An O represents any other adverse event (perforation, hematoma, fistula, transfusion needed, prolonged hospitalization, re-admission, or graft loss, n=11). Some of these events (perforation, graft loss) never occurred in this particular data set.

The first 170 biopsies occurred prior to a major change in procedure, the use of real time ultrasound to help with needle positioning. The three month period from July through September was considered a transition period. There were 20 biopsies performed during this transition. The biopsies from October 2005 onward were considered to be part of the post implementation phase.

The plot below shows the time when certain biopsy events occurred. The shaded region represents the transition period.

Here are some control charts monitoring the frequency of events.

Note that about one in 11 biopsies involves hematuria and that rate is relatively stable before, during, and after the transition.

In contrast, the problems with inadequate tissue have virtually disappeared. there are more than 80 consecutive biopsies since the transition without a single one resulting in inadequate tissue. If you remove this last data point from the calculation of the control limits, you will find that the average number needed to harm prior to the transition was approximately 9. So before the use of ultrasound for kidney biopsies, we were sending every ninth patient back for a second biopsy because of inadequate tissue. After using ultrasound, we have stopped experiencing any problems with inadequate tissue.

Approximately every tenth biopsy required the use of pain control medication. This rate is stable before, during, and after biopsy.

Other adverse events occur in one out of every 20 biopsies on average. We are currently experiencing a large gap in other adverse events, and if this continues for 9 or 10 more patients, we will have evidence that this rate has recently slowed.