File layout for tumor data (all free format)

There are two data files containing the measurements...

(a) 16 lines(investigators) x 12 columns("tumors") as
    in the original article

(b) 16 x 12 = 192 lines, one measurement per line
    with the lines indexed by tumor # and investiagtor #

    i.e.    tumor #   Investigator #    measurement
               1            1                1.3
               1            2                1.5
              ...          ...               ...
               1           16                1.7
               2            1                1.8
              ...          ...               ...
              12           16               13.0

and one data file containing the "true" diameters

tumor diameter
   1   1.8
   2   2.3
   3   2.7
   4   3.5
   5   4.3
   6   4.4
   7   5.5
   8   5.5
   9   6.4
  10   7.5
  11   8.6
  12  14.5

-----------------------------------------------

Excerpts from...

THE EFFECT OF MEASUREMENT ERROR ON THE RESULTS OF THERAPEUTIC 
TRIALS IN ADVANCED CANCER

Charles G Moertel, Mayo Clinic, Rochester, Minnesota
and 
James A Hanley, State University of New York at Buffalo

Cancer 38(7):388-394, 1976

I N T R O D U C T I O N

In recent decades, the practice of cancer medicine and the 
technology of experimental cancer therapy have reached 
progressively higher levels of scientific sophistication. 
Preclinical screening and smallŅand largeŅanimal 
toxicological studies provide the investigator with a great 
wealth of data for his clinical trials. Remarkable measuring 
equipment and refined methodology can dissect the 
pharmacokinetics and the physiologic and immunologic effects 
of a new treatment modality with almost infinite detail. 
Similarly, the laudable new trends towards more objective and 
more controlled clinical investigation in cancer therapy have 
led to the elucidation of the many principles of proper 
scientific experimentation. Emphasis has been placed, and 
rightly so, on careful study planning, clarity in the 
statement of study objectives, thoughtful case selection, 
meticulous treatment methodology, and the efficient use and 
correct interpretation of study results.

There is, however, one essential element of this 
experimentation which is perhaps too frequently forgotten 
amidst such technical sophistry, namely, the actual 
measurement of the study end point. The culmination of most 
experimental therapeutic trials for solid tumors occurs when 
a man places a ruler or caliper over a lump and attempts to 
estimate its size. With this is introduced the inevitable 
factor of human error. Although the ultimate aim of therapy 
is increased survival, only few of our current approaches 
achieve that goal. To search for antitumor activity in a new 
modality by using survival as an endpoint is a far too 
complex and time-consuming effort and one that is frequently 
confused by the multiple therapies that may be attempted in 
any single patient. Apart from some attempts to examine 
optimum methods of measuring lesions visible on 
roentgenograms(1) this vital area of cancer treatment 
methodology has been largely ignored in oncology writings. 
Since at present we cannot eliminate the human error factor, 
it would seem advisable to make an effort to understand it, 
to learn how great an effect it can have on the validity of 
our results, and to consider how to defend against it. This 
report deals with an investigation of the sources and 
magnitude of measurement variations which arise in evaluating 
anticancer activity of modalities used in the treatment of 
solid tumors. The results emphasize the serious effects that 
such measurement errors can have on reported results, and 
suggest that a recognition of the limitation of measurement 
accuracy should be a major consideration in the formulation 
of criteria for clinical antitumor activity.

M A T E R I A L S   A N D   M E T H O D S

This study was designed as a simulation of the conditions 
when a clinician measures tumors under the circumstances 
usually encountered in oncologic practice.

Twelve solid spheres were selected, measuring from 1.8 to 
14.5 cm in diameter. It was assumed that this size range 
would cover the sizes usually encountered in measurable 
clinical masses such as subcutaneous, lymph node, and intra-
abdominal tumors. These masses were then arranged in random 
size order on a soft mattress and covered with a layer of 
foam rubber. This layer measured 0.5 in. in thickness for the 
six smaller masses to approximate skin and subcutaneous 
tissue and 1.5 in. for the six larger masses to approximate 
abdominal wall. Each of 16 experienced physicians practicing 
in oncology was then asked to measure the diameter of each 
sphere using the usual technique and equipment (ruler or 
caliper) he employed in clinical practice.   The actual 
"tumor" diameters are shown in Table 1. The participants were 
unaware that "tumors" 5 and 6 were designed to have the same 
diameter and so to provide an estimate of the reproducibility 
of each physician's measurements of tumor size. Tumors 7 and 
8 were also designed for this purpose (the slight difference 
in true diameters 5 and 6 and in 7 and 8 reflects variations 
in the manufacturing process).   These "tumors" were palpably 
very similar to those encountered in clinical practice. The 
setting, however, was a very idealized representation of 
practice conditions where tumors tend to be less accessible, 
nonspherical, and of varying texture, and where the bearer of 
the tumor is not often as immobile and compliant as a 
mattress. The results which follow can thus be viewed as 
conservative estimates of measurement variations occurring 
under real-life clinical conditions.