Inflammatory Bowel Drugs To Go Head-To-Head With PCORI Funding

A number of drug-related comparative effectiveness research projects are approved for PCORI-sponsored research in its second funding cycle. Health IT-related projects also get attention as the institute spends more than $88 million on 51 projects.

The first head-to-head drug trial has emerged in the Patient-Centered Outcomes Research Institute’s second cycle of funding for comparative effectiveness research projects, and a number of other trials that include drug therapy as part of an overall project objective.

The winning grants in PCORI’s second funding cycle were approved by the board at its May 6 meeting. According to the document describing the grant projects, researchers at the University of Pennsylvania will examine the comparative effectiveness of corticosteroids (CS) versus biologic therapies targeting tumor necrosis factor alpha (anti-TNF) for the treatment of inflammatory bowel diseases (IBD) – Crohn’s disease and ulcerative colitis.

Researchers “will test the hypothesis that the efficacy of anti-TNF therapy results in reduced need for bowel resection surgery, fewer serious infections, and reduced short-term mortality risks and, therefore, have a more favorable benefit-to-harm profile than CS for IBD.”

The document identifies three parts to the study:

• Aim 1: Quantify patients’ preferences for relevant treatment outcomes by implementing a discrete choice experiment. Participants will choose between two medical treatment options with various attributes (e.g. the risk of serious infection, treatment failure requiring surgery, death, etc.). Using the methods of conjoint analysis, researchers will compute mean preference weights for each of these attributes.
• Aim 2: Conduct a comparative effectiveness study among Medicare beneficiaries with IBD, comparing the incidence of severe infection, bowel resection surgery and death among new users of anti-TNF therapies and CS.
• Aim 3: Combination of the results of Aims 1 and 2 to compute the relative net benefit of the two treatment strategies after accounting for patient preferences for each one. For each patient, researchers will compute a preference-weighted value for each month of follow-up using an initial treatment carried forward model that allows patients to switch therapies if the first is not effective

“This study will use novel methodology to provide a critically needed assessment of the overall risks and benefits of these two treatment strategies, informed by quantitative patient assessments of therapeutic trade-offs,” the document notes. “The results should lead to improved outcomes for patients with IBD.”

Specific treatments that will be used in the study were not identified. Two anti-TNF therapies are indicated for both Crohn’s disease and ulcerative colitis: AbbVie Inc.’s Humira (adalimumab) and Janssen Biotech Inc.‘s Remicade (infliximab). UCB Group’sCimzia (certolizumab pegol) is indicated for Crohn’s. Janssen’s Simponi (golimumab) has a user fee date in May for an ulcerative colitis indication and has been studied in Crohn’s. A fifth anti-TNF therapy on the market is Enbrel (etanercept), marketed by Amgen Inc. and Pfizer Inc. Those lacking specific indications have been studied and used off-label to treat IBD.

This research project comes as FDA and industry together are seeking temporary endpoints to assess ulcerative colitis drugs (Also see "FDA, Industry Seek Temporary Endpoint For Assessing Ulcerative Colitis Drugs" - Pink Sheet, 1 Oct, 2012.).

Other Drug-Related Projects

In total, the PCORI board of governors approved 51 clinical comparative research projects and will spend $88.6 million across all of them. The applications were in response to the second cycle of broad funding announcements and cover four of the five priority areas identified by PCORI when it released its national priorities and research agenda document in 2012 – addressing disparities; assessment of prevention, diagnosis and treatment options; communication and dissemination; and improving health care systems. The fifth area, involving research infrastructure, is handled in separate funding tracks (Also see "PCORI Plans Detailed Funding Announcement For One Area Of Research Agenda" - Pink Sheet, 19 Mar, 2012.).

PCORI Cycle II: Number Of Projects And Total Funding Awarded Per Research Area

• Addressing disparities: 10, $16.4 million
• Assessment of prevention, diagnosis and treatment options: 20, $33.6 million
• Communication and dissemination: 8, $14 million
• Improving health care systems: 13, $24.5 million

Topics in this funding cycle are developed by researchers, unlike a separate funding track where PCORI will solicit research applications that will answer targeted questions (Also see "PCORI Initiates A Targeted Approach To Research At November Meeting" - Pink Sheet, 3 Dec, 2012.). In this second cycle of funding based on the broad research priorities, there are seven drug-related research topics, up from two topics out of 25 research grants issued in December 2012 during the first cycle, which was based on the national priorities and research agenda (Also see "Two Drug-Specific Projects In PCORI’s Initial Comparative Research Roster" - Pink Sheet, 20 Dec, 2012.).

Drug-related research topics include:

• Developing a decision aid for administration (intraperitoneal vs. intravenous) of chemotherapy for the treatment of ovarian cancer;
• Comparing patient-centered outcomes after treatment for uterine fibroids, which will look at medication and surgical treatments;
• Comparing treatment preferences among different patient groups with stage IV lung cancer based on drugs with similar survival benefits but different side effects;
• Understanding treatment preferences for prostate cancer that will compare a conjoint analysis intervention to usual care and identify preferred attributes of alternative prostate cancer treatments;
• Comparative effectiveness of a decision aid for therapeutic options in sickle cell disease; and
• Understanding the long-term outcomes of lumbar epidural steroid injections to treat spinal stenosis.

Health IT-Related Projects Prominent

PCORI also is funding a number of health information technology-related projects, including three that focus on using electronic health records.

For example, the project listed above that will compare outcomes after treatment for uterine fibroids will do so through examination of electronic health records linked to insurance claims data and a separate analysis of EHRs from a network of health systems. Other non-drug topics that have a prominent EHR component include understanding the comparative risks and benefits of gender reassignment therapies and screening for physical abuse in children.

Since its inception, PCORI has had its eye on how EHRs can be utilized in comparative effectiveness research (Also see "PCORI Board Eyes Connection Between Health IT Meaningful Use And Comparative Effectiveness Research" - Pink Sheet, 24 Nov, 2010.). More recently, the institute announced initiatives to build data infrastructure (Also see "PCORI To Fund Development Of Data Networks For CER, Clinical Development" - Pink Sheet, 23 Apr, 2013.). And while EHRs are being seen as having potential for improving clinical research, adoption remains a current challenge to gaining full benefit (Also see "Low E-Health Record Adoption Presents Challenge For R&D Use, AstraZeneca Informatics Scientist Says" - Pink Sheet, 22 Apr, 2013.).

But PCORI’s funding of health IT projects goes beyond the use of EHRs. A number of projects involve the development of web-based decision support tools and mobile apps (including one that is iPad-specific). HHS currently is working on a regulatory framework relative to mobile medical apps (Also see "HHS Health IT Regulations Work Group Sets Path Forward" - Medtech Insight, 6 May, 2013.).