Agreement on Outcome in a Cardiovascular RCT
Agreement on Outcome in a Cardiovascular RCT
Background The objective of this study is to describe the agreement between randomized trial outcome assessment by committee and outcomes entirely identified through public registers.
Methods In the CLARICOR trial, 4,372 patients with stable coronary heart disease received a short course of clarithromycin versus placebo and were followed up for 2.6 years. The pertinent hospital records and death certificates had originally been evaluated by the adjudication committee using common definitions of outcomes mapped into a 6-category list. We now mechanically converted the International Classification of Diseases–coded diagnoses of the public registries into the same categories. After cross-tabulation of the committee diagnoses with National Patient Register diagnoses and Register of Causes of Death, we calculate agreement and compare the estimated intervention effects of the 2 data sets.
Results With public register data, the protocol-specified categories were slightly more frequent. Overall agreement was 74% for hospital discharges and 60% for cause of death, but the intervention effect, expressed as a hazard ratio, stayed within 4% of the value originally obtained with the adjudication committee (P≥ .35).
Conclusions Our results show a modest agreement between formal adjudication and outcomes deducible from public registers. However, the estimated intervention effect did not differ noticeably between the 2 data sources. If studies on a wide range of public registers confirm these findings, register outcomes may be considered as a replacement for adjudication committees.
In clinical trials, an adjudication committee (AC) is appointed to classify reports on events that may constitute protocol outcomes. The methods for capturing cases for adjudication and the type of information provided to the AC are heterogeneous. Public registers are rarely used as the source of events, probably due to suspicion of incompleteness and lack of rigor. Most readers will have even stronger reservations against the idea of dispensing with the AC and passing data from public registers directly to the statistical analysis of the trial. However, if the public health care registration system ensures virtually complete registration and reflects definitions that are used in clinical trials, and provided that it remains under the veil of blinded randomization, it is conceivable that register data may be relied on for outcome assessment without seriously affecting estimates of intervention effect.
The purpose of the present study is to describe, within a large randomized clinical trial of patients with ischemic heart disease, the uncertainty inherent in outcomes deducible from public registers when used as a substitute for adjudication and to quantify the agreement between the results that the trial would have had when based on one or the other data set.
Abstract and Introduction
Abstract
Background The objective of this study is to describe the agreement between randomized trial outcome assessment by committee and outcomes entirely identified through public registers.
Methods In the CLARICOR trial, 4,372 patients with stable coronary heart disease received a short course of clarithromycin versus placebo and were followed up for 2.6 years. The pertinent hospital records and death certificates had originally been evaluated by the adjudication committee using common definitions of outcomes mapped into a 6-category list. We now mechanically converted the International Classification of Diseases–coded diagnoses of the public registries into the same categories. After cross-tabulation of the committee diagnoses with National Patient Register diagnoses and Register of Causes of Death, we calculate agreement and compare the estimated intervention effects of the 2 data sets.
Results With public register data, the protocol-specified categories were slightly more frequent. Overall agreement was 74% for hospital discharges and 60% for cause of death, but the intervention effect, expressed as a hazard ratio, stayed within 4% of the value originally obtained with the adjudication committee (P≥ .35).
Conclusions Our results show a modest agreement between formal adjudication and outcomes deducible from public registers. However, the estimated intervention effect did not differ noticeably between the 2 data sources. If studies on a wide range of public registers confirm these findings, register outcomes may be considered as a replacement for adjudication committees.
Introduction
In clinical trials, an adjudication committee (AC) is appointed to classify reports on events that may constitute protocol outcomes. The methods for capturing cases for adjudication and the type of information provided to the AC are heterogeneous. Public registers are rarely used as the source of events, probably due to suspicion of incompleteness and lack of rigor. Most readers will have even stronger reservations against the idea of dispensing with the AC and passing data from public registers directly to the statistical analysis of the trial. However, if the public health care registration system ensures virtually complete registration and reflects definitions that are used in clinical trials, and provided that it remains under the veil of blinded randomization, it is conceivable that register data may be relied on for outcome assessment without seriously affecting estimates of intervention effect.
The purpose of the present study is to describe, within a large randomized clinical trial of patients with ischemic heart disease, the uncertainty inherent in outcomes deducible from public registers when used as a substitute for adjudication and to quantify the agreement between the results that the trial would have had when based on one or the other data set.
