Clinical trial NCT02297126: A Prospective Trial to Assess Cost and Clinical Outcomes of a Clinical Pharmacogenomic Program
Official title: A Prospective Randomized Trial to Assess Cost and Clinical Outcomes of a Clinical Pharmacogenomic Program at Eskenazi Hospital
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adverse Drug Reaction
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
First posted: 2014-11-21
Enrollment: 4465
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 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 outcomes:
measure: 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
timeFrame: Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed
measure: Impact of implementing a Pharmacogenetics program on prescribing patterns within a safety-net healthcare system
timeFrame: Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Eskenazi Health System
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine, Regenstrief Institute, Eskenazi Health
name: Paul R Dexter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University School of Medicine
name: Todd Skaar, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Fulton CR, Zang Y, Desta Z, Rosenman MB, Holmes AM, Decker BS, Zhang Y, T Callaghan J, Pratt VM, Levy KD, Gufford BT, Dexter PR, Skaar TC, Eadon MT. Drug-gene and drug-drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial. Pharmacogenomics. 2019 Apr;20(6):397-408. doi: 10.2217/pgs-2018-0205. Epub 2019 Feb 20.