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Regression Discontinuity Design to Evaluate of Drotrecogin Alpha Effectiveness

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02843685
Recruitment Status : Completed
First Posted : July 26, 2016
Last Update Posted : July 26, 2016
Sponsor:
Information provided by (Responsible Party):
Allan J. Walkey, Boston Medical Center

Brief Summary:

Many health care interventions and medications found to have benefits ("efficacy") in experimental, tightly-controlled, human research trials are later found to lack real-world health benefits ("effectiveness"). Inadequate surveillance of real-world clinical effectiveness may falsely reassure clinicians and those who monitor healthcare quality, propagating unrecognized ineffective or harmful treatments at high costs to patients and society. The failure to translate potential health benefits into realized gains, or to detect unexpected harms in healthcare delivery, stems from a lack of methods with which to robustly measure real-world (in)effectiveness. Current methods to detect changes in outcomes 'before and after' implementation may be biased by secular trends in healthcare practice and outcomes; other methods to compare outcomes for treated and untreated patients may be biased by unmeasured factors.

The current project aims to develop and demonstrate - as a proof-of-concept - the use of a quasi-experimental research method called 'regression discontinuity design (RDD)' in surveillance of real-world clinical effectiveness. RDD had previously found use in the evaluation of educational programs in which students scoring below a threshold were assigned an intervention. The US Department of Education considers RDD designs to have quality similar to randomized trials.


Condition or disease Intervention/treatment
Sepsis Drug: Drotrecogin alfa activated

Detailed Description:

Many health care interventions and medications found to have benefits ("efficacy") in experimental, tightly-controlled, human research trials are later found to lack real-world health benefits ("effectiveness"). Inadequate surveillance of real-world clinical effectiveness may falsely reassure clinicians and those who monitor healthcare quality, propagating unrecognized ineffective or harmful treatments at high costs to patients and society. The failure to translate potential health benefits into realized gains, or to detect unexpected harms in healthcare delivery, stems from a lack of methods with which to robustly measure real-world (in)effectiveness. Current methods to detect changes in outcomes 'before and after' implementation may be biased by secular trends in healthcare practice and outcomes; other methods to compare outcomes for treated and untreated patients may be biased by unmeasured factors.

The current project aims to develop and demonstrate - as a proof-of-concept - the use of a quasi-experimental research method called 'regression discontinuity design (RDD)' in surveillance of real-world clinical effectiveness. RDD had previously found use in the evaluation of educational programs in which students scoring below a threshold were assigned an intervention. The US Department of Education considers RDD designs to have quality similar to randomized trials. However, RDD has not been rigorously evaluated in the context of evaluating clinical effectiveness. RDD can be used whenever an intervention is given to patients scoring above a threshold on a continuous biomarker or risk score. This scenario often arises in clinical practice, in which thresholds are used to identify and treat 'high risk' patients. In RDD, outcomes are compared for patients just above and just below the threshold, who are similar, but receive different treatments.

The project will study the use of RDD in evaluating the real-world effectiveness of drotrecogin alpha, a medication that was recommended by the FDA to be given to critically ill patients with severe sepsis at high risk for mortality (APACHE score > 25). Drotrecogin alpha was shown to potentially have "effectiveness" using traditional methods of real-world research, but was eventually shown to not be clinically efficacious in subsequent large randomized trials. The present proposal is a 'proof-of-concept' study that will allow evaluation of effect estimates derived from RDD methods to those of gold standard, pooled randomized trial results. The demonstration of feasibility for a new research method, such as RDD, to evaluate real-world clinical effectiveness would be a major leap forward in the ability monitor for potential real world benefits and harms of new treatments.

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Study Type : Observational
Actual Enrollment : 12492 participants
Time Perspective: Retrospective
Official Title: Regression Discontinuity Designs to Evaluate Real-world Effectiveness: a Case Study of Drotrecogin Alpha
Study Start Date : December 2002
Actual Primary Completion Date : December 2005

Intervention Details:
  • Drug: Drotrecogin alfa activated
    Other Name: Xigris


Primary Outcome Measures :
  1. Relative risk reduction for mortality [ Time Frame: Duration of hospitalization, on average approximately 14 days ]
    The study will evaluate the change in the relationship between APACHE II scores and hospital mortality rate at the APACHE II threshold score of 25


Secondary Outcome Measures :
  1. APACHE II scores at which drotrecogin alpha was used [ Time Frame: Baseline ]
    Evaluation of drotrecogin alpha practice patterns at APACHE II score of 25

  2. Change in mortality risk over time [ Time Frame: 3 years ]
    The study will assess interaction between year and relative risk for mortality associated with drotrecogin alpha



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

An International Observational Study Among Severe Sepsis Patients Treated in the Intensive Care Unit (PROGRESS severe sepsis registry).

The PROGRESS registry of severe sepsis cases is a unique resource that contains data linking APACHE scores, drotrecogin alpha administration, and hospital mortality outcomes, providing an opportunity to study RDD as a novel method of comparative effectiveness research, and compare results derived from RDD to prior studies using more traditional comparative effectiveness designs (i.e., propensity score adjustment).

Criteria

Inclusion Criteria:

  • Included in PROGRESS severe sepsis registry

Exclusion Criteria:

  • None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02843685


Locations
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United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Publications:
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Responsible Party: Allan J. Walkey, Assistant Professor of Medicine, Boston Medical Center
ClinicalTrials.gov Identifier: NCT02843685    
Other Study ID Numbers: H-35010
First Posted: July 26, 2016    Key Record Dates
Last Update Posted: July 26, 2016
Last Verified: July 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data (IPD) is only available through consultation with the original PROGRESS registry study sponsor through https://www.clinicalstudydatarequest.com/
Additional relevant MeSH terms:
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Drotrecogin alfa activated
Anti-Infective Agents