Monitoring adverse events during peritoneal dialysis

Steve Simon

2007-11-15

Categories: Blog post Tags: Adverse events in clinical trials

One of the doctors I was working with had an interesting data set examining adverse events in patients with peritoneal dialysis. These patients start treatment with peritoneal dialysis on a specific day and are followed until they stop this treatment. Reasons for stopping peritoneal dialysis might be that the patient got better and no longer needed any treatment, the patient got worse and needed to switch to hemodialysis, or the patient died. Patients who moved out of town presumably continued their dialysis, but they were lost to follow-up in this particular study. There were two adverse events examined: exit site infections, and peritonitis. Although I ran several complex analyses on this data set, I thought it might be useful to look at a simpler approach to monitoring the frequency of adverse events using control charts.

Here’s the data on when patients began treatment and when they ended their treatment.

id t0 t1 0 58 680 1 95 1416 2 189 1247 3 207 532 4 402 1136 5 412 501 6 431 1851 7 550 1414 8 581 1339 9 770 2325 10 809 1498 11 841 1339 12 880 1563 13 903 2664 14 939 1451 15 980 2920 16 1106 2103 17 1107 1291 18 1155 1792 19 1159 1654 20 1200 1968 21 1247 1574 22 1422 2247 23 1449 1544 24 1499 2310 25 1582 1755 26 1677 2142 27 1786 2920 28 1799 2108 29 1803 2729 30 2097 2723 31 2101 2639 32 2225 2419 33 2254 2920 34 2496 2920 35 2500 2920 36 2507 2920 37 2562 2730 38 2590 2870 39 2663 2920 40 2701 2838 41 2711 2920

The first column is the patient id, the second column is when the patient started dialysis (number of days since the start of the review period), and the third column is when the patient ended dialysis (again in number of days).

There were 42 patients in this study. The average patient stayed in the study for 640 days (1.8 years). We will divide the number of days by 365 in most graphical presentations of the data to show time in years rather than days.

This graph shows the cumulative number of patients at risk of an adverse event at any time point in the review period.

The vertical line segments at the bottom of the graph represent the times that patients began dialysis and the segments at the top of the graph represent the times that patients ended dialysis. Each time a patent begins dialysis, the graph jumps up one unit. Every time a patient ends dialysis, the graph drops one unit. At the busiest time, there were 17 patients on dialysis. The graph falls to zero at 8 years, not because all patients were removed from dialysis, but because that represented the end of the observation period.

Notice that this graph generally climbs for the first three years, drops of a bit then is roughly level for years 4 through 8. This is not surprising because only patients who began dialysis during the eight year observation window were included in the study.

Here are the times of exit site infections:

id tx 0 643 0 657 1 143 1 203 1 756 1 900 1 1122 1 1331 2 596 3 231 4 905 4 953 4 986 6 680 6 1273 6 1410 6 1485 6 1584 7 967 9 1292 12 1442 13 1331 13 1351 13 2528 13 2658 14 949 14 1261 14 1447 16 1250 21 1267 27 1947 33 2520 33 2767 35 2769

Notice that some patients experience more than one exit site infection and some patients experience no infections. You might already notice something interesting with the data. About half of the events have three digit days (days in the hundreds). Since the full time range is from zero to a bit less than 3 thousand, you would expect only about a third of these events to have three digit days. This is possible evidence that these events occurred more frequently early in the review period rather than later. A careful analysis, of course, would have to control for the number of patients at risk during these time intervals.

Here is the data on times of peritonitis.

id tx 0 218 1 652 1 1265 1 1328 3 237 7 641 7 1004 7 1080 9 978 9 1036 9 1236 9 1974 9 2116 10 904 10 1305 13 1815 13 1983 13 2082 14 949 15 2859 20 1959 24 1977 24 2089 25 1620 25 1641 27 1803 27 2354 27 2520 28 1809 28 2054 33 2351 41 2740 41 2755

The graph below shows the cumulative number of patient years over the eight year study (you can get this by integrating the figure shown above). This graph also notes the occurrence of exit site infections using a red plus sign.

Here’s a second graph with occurrence of peritonitis marked with a red plus sign.

The horizontal distance between successive plus signs represents the waiting time in years between the successive patients. The vertical distance between successive plus signs represents the waiting time in patient-years. It’s a subtle but important difference. By calculating the number of patient-years between successive events, you can It adjusts for the fact that during the first two or three years of observation, there were fewer patient-years of data compared to successive years.

If you plot the patient-years between successive exit site infections, you will see the following control chart.

The gray region represents the first four years of the study. After the fourth year, an intervention was implemented to reduce adverse events. You can see that it had a dramatic impact at first, with the hospital twice waiting over 10 patient year between events shortly after the intervention started. More recently, it looks as if the waiting time has slipped back at least partway to the norm.

Here’s the plot for peritonitis events.

Notice that there is no evidence that peritonitis is becoming a rarer event after the intervention.