Regression Discontinuity Design to Evaluate of Drotrecogin Alpha Effectiveness

NCT02843685 | Completed

• 1 other identifier: H-35010
• Study Type: observational
• Target: 12,492
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Outcome Measures

Primary Outcomes (1)

• Relative risk reduction for mortality

  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

  Duration of hospitalization, on average approximately 14 days

Secondary Outcomes (2)

• APACHE II scores at which drotrecogin alpha was used

  Baseline

• Change in mortality risk over time

  3 years

Interventions

Drotrecogin alfa activated DRUG

Also known as: Xigris

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• Included in PROGRESS severe sepsis registry

You may not qualify if:

• None

Sponsors & Collaborators

• Boston Medical Center: lead

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Related Publications (3)

• Martin G, Brunkhorst FM, Janes JM, Reinhart K, Sundin DP, Garnett K, Beale R. The international PROGRESS registry of patients with severe sepsis: drotrecogin alfa (activated) use and patient outcomes. Crit Care. 2009;13(3):R103. doi: 10.1186/cc7936. Epub 2009 Jun 30.

  PMID: 19566927 BACKGROUND

• Beale R, Reinhart K, Brunkhorst FM, Dobb G, Levy M, Martin G, Martin C, Ramsey G, Silva E, Vallet B, Vincent JL, Janes JM, Sarwat S, Williams MD; PROGRESS Advisory Board. Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry. Infection. 2009 Jun;37(3):222-32. doi: 10.1007/s15010-008-8203-z. Epub 2009 Apr 28.

  PMID: 19404580 BACKGROUND

• Walkey AJ, Bor J. Risk-based Heterogeneity of Treatment Effect in Trials and Implications for Surveillance of Clinical Effectiveness Using Regression Discontinuity Designs. Am J Respir Crit Care Med. 2015 Dec 1;192(11):1399. doi: 10.1164/rccm.201508-1533LE. No abstract available.

  PMID: 26623693 BACKGROUND

MeSH Terms

Conditions

Sepsis

Interventions

drotrecogin alfa activated

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 15, 2016
• First Posted: July 26, 2016
• Study Start: December 1, 2002
• Primary Completion: December 1, 2005
• Last Updated: July 26, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)