A Prospective Trial to Assess Cost and Clinical Outcomes of a Clinical Pharmacogenomic Program

Adverse Drug Reaction Clinical Trial

— INGenious  

Official title:

A Prospective Randomized Trial to Assess Cost and Clinical Outcomes of a Clinical Pharmacogenomic Program at Eskenazi Hospital

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02297126
• Other study ID #: 1401206188
• Secondary ID: U01HG007762-01
• Status: Completed
• Phase: N/A
• Start date: March 2015
• Est. completion date: May 3, 2019

Study information

• Verified date: January 2021
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The INGenious trial will prospectively enroll a total of 6,000 patients, with 2,000 patients assigned to a pharmacogenetic testing arm and 4,000 to a control arm who will be followed, but not tested. It is randomized between an intervention arm and one that receives no intervention in order that the genotyped group can be compared with one in which undisturbed, routine clinical care is carried out in patients taking the same drugs. Both arms will be followed for a year after being prescribed a targeted medication. Patients randomized into the intervention arm that are prescribed one or more of the 24 targeted index medication will receive pharmacogenomic testing using a custom micro-array measuring 51 Single nucleotide polymorphisms in 16 genes. The study is being conducted by the Indiana University School of Medicine and the Indiana University Institute of Personalized Medicine in collaboration with the Eskenazi and Indiana University Health Systems and will evaluate the economic and clinical outcomes associated with embedding a pharmacogenomics program in a system that serves as the primary health care safety-net in Indianapolis, Indiana. By successfully implementing a pharmacogenomics program and integrating it with the Electronic Health Record and Clinical Decision Support system, physicians will be able to optimize patient care by delivering tailored therapeutic decisions based on the patient's individual genetics.

Description:

Indiana University School of Medicine and the Indiana University Institute of Personalized Medicine in collaboration with the Eskenazi Health and IUH Systems will be conducting a NIH funded randomized trial beginning in 2014. The study will evaluate the economic and clinical outcomes of associated with embedding a pharmacogenomics program in a system that serves as a health care safety-net in Indianapolis, Indiana, and handles over 1.2 million outpatient visits a year at its hospital and network of 10 community health centers. There are over 990,000 outpatient visits and 15,000 adult admissions annually, and the payor mix includes 45% uninsured, 26% Medicaid and 18% Medicare patients. This health care system has more than 40 years of experience in digital medical record implementation and a proven track record of innovation in medical informatics that is based in the Regenstrief Institute.

The goal of Personalized Medicine (PM) is to implement advances in biomarker pharmacology, molecular diagnostics and genomics to improve the health of patients afflicted by a wide range of medical conditions. Dramatic advances in genomics have identified numerous disease/therapeutic associations now placing this goal within sight. For the full benefits of personalized genomic medicine to be realized, it is now critical that progress made on a small scale be extended. The fruits of outstanding scientific discovery are often enjoyed by a small number of academic medical centers but are not scalable, and therefore not available to the masses of patients found in larger health care systems. In addition, such advances often bypass underserved populations, resulting significant inequalities of care.

Study Aims:

Aim 1: To test the hypothesis that a Clinical Laboratory Improvement Amendment certified genotyping targeted at 24 widely used drugs is associated with significant reductions in hospital and outpatient economic costs incurred over 1 year.

Aim2: To test whether pharmacogenetic testing is associated with significant improvements in clinical outcomes over 1 year.

The INGENIOUS trial will enroll a total of 6,000 patients, with 2,000 patients assigned to a pharmacogenetic testing arm and 4,000 to a control arm who will be followed, but not tested. The study is prospective since practice patterns change, and retrospective designs cannot be used to assess the impact of a prospective change. It is randomized between an intervention arm and one that receives no intervention in order that a genotyped group can be compared with one in which undisturbed, routine clinical care is carried out in patients taking the same drugs. Both arms will be followed for a year. Subjects will be enrolled starting at 6 months into the funding period, and investigators will enroll subjects for a total of 2 years, so that the last person enrolled will be at 2.5 years, and follow up will be completed at 3.5 years, allowing 6 months for analysis at the end of the study. A pharmacogenetic test, involving 51 Single nucleotide polymorphisms in 16 genes will be carried out at the beginning of the study in patients in the testing arm upon prompting by an index medication: one of 24 selected as being supported by validated guidelines.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4465
• Est. completion date: May 3, 2019
• Est. primary completion date: May 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients will be eligible for inclusion if they are prescribed one of the 27 index medications for the first time, defined as there being no recorded prescription in the Eskenazi, Indiana University Health or Indiana Patient Care (INPC) system over the past year. The inclusion criteria that will be adhered to will be:

1. Able and willing consent to participation in the trial;

2. Adults aged 18 and over;

3. Receiving care at Eskenazi Health or Indiana University Health Systems for 1 year or more;

4. Prescribed an index medication.

5. No documented prescription of the index medication for the past year.

6. The study limit of enrollment (500) for that medication has not been reached

7. A single tube of whole blood can be obtained, and

8. Able to follow study procedures. -

Exclusion Criteria:

No subject will be excluded from the study on the basis of ethnicity or race. We will include all minorities.

Patients will be excluded if they:

1. Cannot or do not consent to participate;

2. are unable to provide 5cc of whole blood, or it cannot be obtained;

3. if they are an employee or student under the supervision of any of the investigators.

Related Conditions & MeSH terms

• Adverse Drug Reaction
• Drug-Related Side Effects and Adverse Reactions

Intervention

Other:
• Pharmacogenetic Intervention Arm (pharmacogenetic testing)
In the design of this trial, pharmacogenetic testing will be triggered by the incident prescription of one or more of the targeted medications listed in the control arm. The pharmacogenetic array to be used incorporates 51 genetic variants for the following 16 genes/transporters: ATP-binding cassette sub-family C member 2, ATP-binding cassette, sub-family C, member 4, Cytochrome P450 2B6, Cytochrome P450 2C19, Cytochrome P450 2C9, Cytochrome P450 2D6, Cytochrome P450 3A4/3A5, Cytochrome P450 4F2, Dihydropyrimidine dehydrogenase, Glucose-6-Phosphate Dehydrogenase, Human Leukocyte antigen-B, I interleukin-28B, Inosine Triphosphatase, Solute Carrier Organic Anion Transporter Family, Member 1B, Thiopurine methyltransferase and V vitamin K epoxide reductase complex, subunit 1.

Locations

Country	Name	City	State
United States	Eskenazi Health System	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Levy KD, Decker BS, Carpenter JS, Flockhart DA, Dexter PR, Desta Z, Skaar TC. Prerequisites to implementing a pharmacogenomics program in a large health-care system. Clin Pharmacol Ther. 2014 Sep;96(3):307-9. doi: 10.1038/clpt.2014.101. Epub 2014 May 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Financial impact on the total cost of patient care resulting from implementation of a Pharmacogenetics testing program within a safety-net and Academic healthcare system	Analysis of cost of care (measured in U.S. dollars) data from the Eskenazi and Indiana University Health electronic medical records and billing systems for patients in the study. Charge data collected from monthly Eskenazi and IU Health System reports generated for the state hospital association. Categories of inpatient and outpatient charges include costs for medications, facility, laboratory, treatment, professional, and other sources. Data will be collected for each patient in the control and intervention arm beginning the day that the treating physician prescribes one or more targeted medication and will continue to be collected for 12 calendar months. Study enrollment period 2.5 years	Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed
Secondary	Impact of implementing a Pharmacogenetics program on Clinical Outcomes (incidence and severity of adverse events, frequency of healthcare visits, length of hospital stay, and readmissions) within a safety-net and Academic healthcare system	For each patient in the study, investigators from the Regenstrief Institute will collect 12 months of data from the Eskenazi and IUH electronic medical records and informatics systems beginning when one or more targeted medications are prescribed. Outcome measures include: number of patient admissions, readmissions, number of emergency department visits, number of clinic visits and returns to clinic. Data collected includes reported adverse drug reactions related to the targeted medications (utilizing text in the physician notes section of the medical record and records entered using International Classification of Diseases coding convention	Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed
Secondary	Impact of implementing a Pharmacogenetics program on prescribing patterns within a safety-net healthcare system	Prescribing data will be collected for each patient in the control and intervention arm beginning the day that the treating physician prescribes one or more targeted medication and will continue to be collected for 12 calendar months. Study enrollment period 2.5 years. Medication possession ratio for index medications used to determine whether a change in drug regimen was implemented for the intervention versus the control arm.	Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed