The so-called 'placebo effect' in benign prostatic hyperplasia treatment trials represents partially a conditional regression to the mean induced by censoring

Scott M. Sech, Juan D. Montoya, Pablo A. Bernier, Emma Barnboym, Sherril Brown, Allison Gregory, Claus Roehrborn

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objectives. To study the variability of assessment instruments (symptom questionnaires and flow rate recordings) in healthy volunteers during repeat administration in short intervals. To study the effect of inclusion criteria- based censoring of patients during screening for benign prostatic hyperplasia (BPH) treatment trials on the outcome of subsequent tests. Methods. One hundred forty-five male volunteers without known prostatic diseases with a mean age of 52 years (range 23 to 83) were given the American Urological Association (AUA) Symptom Index (SI), BPH Impact Index (II). Quality of Life (QOL) score, and a flow rate recording twice 10 to 20 days apart without any healthcare intervention. Data were collected and analyzed after typical BPH trial criteria were applied to the first test, and patients who did not 'qualify' were censored. Results. Good correlation exists between two closely spaced administrations of the AUA SI, BPH II, QOL score, and flow rate recordings in healthy male volunteers with correlation coefficients between 0.73 and 0.89. Censoring patients and excluding them from the analysis of the second test based on typical BPH trial criteria induces a regression to the mean phenomenon, which results in an artificial improvement in these outcome parameters. The magnitude of the improvement increases as the selection and censoring criteria tighten. The mean differences between the first and second test range from 1.4 to 1.7 mL/s for the peak flow rate, from -1.0 to -1.4 for the AUA SI, and from -0.4 to -0.8 for the BPH II. All these differences induced solely by censoring with resulting regression to the mean are statistically significant. Conclusions. Censoring of patients based on inclusion and exclusion criteria is typical for BPH treatment trials. One of the under-recognized effects of censoring is a regression to the mean, which leads to an apparent improvement in the outcome parameters assessed. In both placebo or sham-controlled trials, as well as in clinical series without controls, one must keep this effect and its relative magnitude in mind, and interpret the data from such trials with appropriate caution.

Original languageEnglish (US)
Pages (from-to)242-250
Number of pages9
JournalUrology
Volume51
Issue number2
DOIs
StatePublished - Feb 1998

Fingerprint

Placebo Effect
Prostatic Hyperplasia
Therapeutics
Healthy Volunteers
Quality of Life
Prostatic Diseases
Symptom Assessment
Patient Selection
Volunteers
Placebos
Delivery of Health Care

ASJC Scopus subject areas

  • Urology

Cite this

The so-called 'placebo effect' in benign prostatic hyperplasia treatment trials represents partially a conditional regression to the mean induced by censoring. / Sech, Scott M.; Montoya, Juan D.; Bernier, Pablo A.; Barnboym, Emma; Brown, Sherril; Gregory, Allison; Roehrborn, Claus.

In: Urology, Vol. 51, No. 2, 02.1998, p. 242-250.

Research output: Contribution to journalArticle

Sech, Scott M. ; Montoya, Juan D. ; Bernier, Pablo A. ; Barnboym, Emma ; Brown, Sherril ; Gregory, Allison ; Roehrborn, Claus. / The so-called 'placebo effect' in benign prostatic hyperplasia treatment trials represents partially a conditional regression to the mean induced by censoring. In: Urology. 1998 ; Vol. 51, No. 2. pp. 242-250.
@article{400d7f67769742ecb144fd91e72e4c84,
title = "The so-called 'placebo effect' in benign prostatic hyperplasia treatment trials represents partially a conditional regression to the mean induced by censoring",
abstract = "Objectives. To study the variability of assessment instruments (symptom questionnaires and flow rate recordings) in healthy volunteers during repeat administration in short intervals. To study the effect of inclusion criteria- based censoring of patients during screening for benign prostatic hyperplasia (BPH) treatment trials on the outcome of subsequent tests. Methods. One hundred forty-five male volunteers without known prostatic diseases with a mean age of 52 years (range 23 to 83) were given the American Urological Association (AUA) Symptom Index (SI), BPH Impact Index (II). Quality of Life (QOL) score, and a flow rate recording twice 10 to 20 days apart without any healthcare intervention. Data were collected and analyzed after typical BPH trial criteria were applied to the first test, and patients who did not 'qualify' were censored. Results. Good correlation exists between two closely spaced administrations of the AUA SI, BPH II, QOL score, and flow rate recordings in healthy male volunteers with correlation coefficients between 0.73 and 0.89. Censoring patients and excluding them from the analysis of the second test based on typical BPH trial criteria induces a regression to the mean phenomenon, which results in an artificial improvement in these outcome parameters. The magnitude of the improvement increases as the selection and censoring criteria tighten. The mean differences between the first and second test range from 1.4 to 1.7 mL/s for the peak flow rate, from -1.0 to -1.4 for the AUA SI, and from -0.4 to -0.8 for the BPH II. All these differences induced solely by censoring with resulting regression to the mean are statistically significant. Conclusions. Censoring of patients based on inclusion and exclusion criteria is typical for BPH treatment trials. One of the under-recognized effects of censoring is a regression to the mean, which leads to an apparent improvement in the outcome parameters assessed. In both placebo or sham-controlled trials, as well as in clinical series without controls, one must keep this effect and its relative magnitude in mind, and interpret the data from such trials with appropriate caution.",
author = "Sech, {Scott M.} and Montoya, {Juan D.} and Bernier, {Pablo A.} and Emma Barnboym and Sherril Brown and Allison Gregory and Claus Roehrborn",
year = "1998",
month = "2",
doi = "10.1016/S0090-4295(97)00609-2",
language = "English (US)",
volume = "51",
pages = "242--250",
journal = "Urology",
issn = "0090-4295",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - The so-called 'placebo effect' in benign prostatic hyperplasia treatment trials represents partially a conditional regression to the mean induced by censoring

AU - Sech, Scott M.

AU - Montoya, Juan D.

AU - Bernier, Pablo A.

AU - Barnboym, Emma

AU - Brown, Sherril

AU - Gregory, Allison

AU - Roehrborn, Claus

PY - 1998/2

Y1 - 1998/2

N2 - Objectives. To study the variability of assessment instruments (symptom questionnaires and flow rate recordings) in healthy volunteers during repeat administration in short intervals. To study the effect of inclusion criteria- based censoring of patients during screening for benign prostatic hyperplasia (BPH) treatment trials on the outcome of subsequent tests. Methods. One hundred forty-five male volunteers without known prostatic diseases with a mean age of 52 years (range 23 to 83) were given the American Urological Association (AUA) Symptom Index (SI), BPH Impact Index (II). Quality of Life (QOL) score, and a flow rate recording twice 10 to 20 days apart without any healthcare intervention. Data were collected and analyzed after typical BPH trial criteria were applied to the first test, and patients who did not 'qualify' were censored. Results. Good correlation exists between two closely spaced administrations of the AUA SI, BPH II, QOL score, and flow rate recordings in healthy male volunteers with correlation coefficients between 0.73 and 0.89. Censoring patients and excluding them from the analysis of the second test based on typical BPH trial criteria induces a regression to the mean phenomenon, which results in an artificial improvement in these outcome parameters. The magnitude of the improvement increases as the selection and censoring criteria tighten. The mean differences between the first and second test range from 1.4 to 1.7 mL/s for the peak flow rate, from -1.0 to -1.4 for the AUA SI, and from -0.4 to -0.8 for the BPH II. All these differences induced solely by censoring with resulting regression to the mean are statistically significant. Conclusions. Censoring of patients based on inclusion and exclusion criteria is typical for BPH treatment trials. One of the under-recognized effects of censoring is a regression to the mean, which leads to an apparent improvement in the outcome parameters assessed. In both placebo or sham-controlled trials, as well as in clinical series without controls, one must keep this effect and its relative magnitude in mind, and interpret the data from such trials with appropriate caution.

AB - Objectives. To study the variability of assessment instruments (symptom questionnaires and flow rate recordings) in healthy volunteers during repeat administration in short intervals. To study the effect of inclusion criteria- based censoring of patients during screening for benign prostatic hyperplasia (BPH) treatment trials on the outcome of subsequent tests. Methods. One hundred forty-five male volunteers without known prostatic diseases with a mean age of 52 years (range 23 to 83) were given the American Urological Association (AUA) Symptom Index (SI), BPH Impact Index (II). Quality of Life (QOL) score, and a flow rate recording twice 10 to 20 days apart without any healthcare intervention. Data were collected and analyzed after typical BPH trial criteria were applied to the first test, and patients who did not 'qualify' were censored. Results. Good correlation exists between two closely spaced administrations of the AUA SI, BPH II, QOL score, and flow rate recordings in healthy male volunteers with correlation coefficients between 0.73 and 0.89. Censoring patients and excluding them from the analysis of the second test based on typical BPH trial criteria induces a regression to the mean phenomenon, which results in an artificial improvement in these outcome parameters. The magnitude of the improvement increases as the selection and censoring criteria tighten. The mean differences between the first and second test range from 1.4 to 1.7 mL/s for the peak flow rate, from -1.0 to -1.4 for the AUA SI, and from -0.4 to -0.8 for the BPH II. All these differences induced solely by censoring with resulting regression to the mean are statistically significant. Conclusions. Censoring of patients based on inclusion and exclusion criteria is typical for BPH treatment trials. One of the under-recognized effects of censoring is a regression to the mean, which leads to an apparent improvement in the outcome parameters assessed. In both placebo or sham-controlled trials, as well as in clinical series without controls, one must keep this effect and its relative magnitude in mind, and interpret the data from such trials with appropriate caution.

UR - http://www.scopus.com/inward/record.url?scp=0032005456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032005456&partnerID=8YFLogxK

U2 - 10.1016/S0090-4295(97)00609-2

DO - 10.1016/S0090-4295(97)00609-2

M3 - Article

C2 - 9495705

AN - SCOPUS:0032005456

VL - 51

SP - 242

EP - 250

JO - Urology

JF - Urology

SN - 0090-4295

IS - 2

ER -