Center for Pediatric Clinical Effectiveness

Research Spotlight

Richard Aplenc MD PhD CPCE Faculty Member Assistant Professor of Pediatrics Division of Oncology	Brian T Fisher DO MPH MSCE CPCE Faculty Member Assistant Professor of Pediatrics Division of Infectious Diseases
Research Interests: Pediatric pharmacogenomics	Research Interests: Infections in Immunocompromised children

Dr. Aplenc is an Associate Professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania and an Associate Physician and Section Chief for Hematologic Malignancies at The Children's Hospital of Philadelphia. He is a faculty member in the Center for Pediatric Clinical Effectiveness.

Dr. Aplenc's research focus is in pediatric pharmacogenomics. He is funded by NIH for studies aimed to determine the genetic predictors of treatment response (particularly relapse and infection risk) for pediatric acute myeloid leukemia (AML) and for his research using administrative/billing data to supplement National Cancer Institute funded cooperative oncology group clinical trials. He also studies the clinical epidemiology of risk factors for treatment complications and outcome disparities in administrative data sets such as the Pediatric Health Information Systems (PHIS) database, and is involved in developing new agents to improve the outcomes of patients with relapsed AML and implementing Phase III clinical trials for patients with AML in the Children's Oncology Group (COG). COG is the largest international pediatric cooperative oncology group, and enrolls approximately 4,400 patients annually on therapeutic trials.

Dr Fisher is an Assistant Professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania, an attending physician in the Division of Infectious Diseases at CHOP and an Associate Scholar at the Center for Clinical Epidemiology and Biostatistics. He is a faculty member of the Center for Pediatric Clinical Effectiveness.

Dr Fisher contributes considerable time to COG's Supportive Care Division. He serves as a committee member or vice-chair on three clinical trials designed to evaluate the efficacy of antibacterial and antifungal prophylaxis in pediatric patients with neutropenia. He is the PI of two ancillary studies to the COG trials, which evaluate the impact of antibiotic prophylaxis on resistance of colonizing bacteria and determine the utility of two biomarkers for the early identification of invasive fungal infections. He also leads an NIH funded investigation of the impact of adenovirus in children receiving solid organ and hematopoietic stem cell transplantations.

Dr. Aplenc and Dr. Fisher collaborate on a number of studies addressing various clinical epidemiology research questions. One current project focuses on leveraging existing administrative data to improve toxicity monitoring and outcome analysis for children treated on COG Phase III trials for de novo AML. They are working to improve toxicity monitoring by merging data from COG with the PHIS database, to estimate treatment associated resource utilization and costs, and to develop the COG-PHIS merged data set as a platform for answering important clinical epidemiology questions.

The PHIS database includes data from 44 pediatric hospitals that account for approximately 85% of the pediatric care provided by free-standing pediatric hospitals in the US and approximately 40% of enrollments on COG AML trials. These merged data combine COG's extensive cancer molecular phenotype information (cytogenetics, molecular studies, and minimal residual disease levels) and validated outcome data (relapse, death) with PHIS's daily charge data (clinical resources, medications, procedures) and ICD9 discharge diagnosis code data. Drs. Aplenc and Fisher hypothesize that the merged data will more accurately report adverse events (AE) than the COG data alone and that merged data can be used to monitor Phase III clinical trials prospectively for toxicities. Finally, they hypothesize that the COG-PHIS merged data will enable description of standardized costs of treatment by regimen arm and enable analyses of cost variation.

The COG/PHIS merge represents a significant methodological advancement and important step to improve toxicity monitoring and outcome analysis in cooperative group oncology trials. Through this collaboration, Dr. Aplenc and Fisher hope to improve the efficiency and effectiveness of the clinical trials system to expedite the development of new treatments for cancer. Drs. Aplenc and Fisher believe this approach will be applicable to other pediatric as well as adult malignancies, thus improving care for cancer patients of all ages.

Works-in-Progress Sessions

CPCE Works-in-Progress sessions bring together clinical effectiveness researchers across the hospital to discuss research projects that are in various stages of development, from protocol development all the way to data analysis, interpretation, and publication. Faculty as well as fellows interested in receiving feedback on their research are welcome to present. These sessions also provide a venue to discuss potential collaborative responses to requests for applications and/or program project grants. Works-in-progress Sessions are held one to two times per month from September through June. If you have a research project you would like to present, please email labregom@email.chop.edu.

CPCE Works-in-progress Sessions qualify for Category 2 CME credit. Use the self-reporting log to record your attendance. You can also obtain documentation of attendance at CPCE Works-in-progress Sessions by contacting Debra Hillman at hillman@email.chop.edu.

For a schedule of upcoming Works-in-progress Sessions, please check the CPCE calendar.

Pilot Grant Program

CPCE offers awards twice each year through its Pilot Grant Program. The purpose of this program is to promote and support CHOP investigators in clinical effectiveness pilot research studies that will attract external support for large-scale studies. Investigators from all CHOP departments and divisions, including fellows in their final year of fellowship transitioning to a faculty position at CHOP, are encouraged to apply. Selected proposals will be supported for up to a maximum of $10,000 for one year. Projects should be able to be completed within one year.

Important Eligibility Notes:
1) Only proposals meeting the following definitions will be reviewed and considered for award.

Clinical Effectiveness Research is research designed to produce evidence of what works best for treating, diagnosing and preventing disease.

A Pilot Study is a small study, conducted in preparation for the larger research study, in which study feasibility is tested and preliminary data are collected.

2) Studies already in progress or partially funded will not be supported.

3) Re-submissions are by invitation only. We will notify you if your submission qualifies to be resubmitted for a future funding cycle.

4) The review process will consist of two rounds. Round one will determine if proposal meets the definition of clinical effectiveness pilot study and is of sufficient quality for further review. ONLY PROPOSALS THAT QUALIFY FOR THE SECOND ROUND WILL BE CRITIQUED AND SCORED.

Application and Submission Process:

• Please submit proposals in NIH format to include project summary/abstract, specific aims, and a research strategy section which includes significance, innovation and approach. (5 page maximum)
• Proposals must also include a cover page, an investigator biosketch in NIH format and project budget, budget justification, and references. (not included in 5 page maximum)
• Budgets must be reviewed by your business manager prior to submission.
• Funding may not be used for investigator salary support. Staff salaries are allowable budget items.
• There are two submission deadlines per year. The 2013 deadlines are Monday, April 1 (awards announced Wednesday, May 1) and Tuesday, October 1 (awards announced Friday, November 1).
• Selected applications must show documentation of IRB submission within 30 days of award notification.
• Proposals submitted for other awards (e.g., Foerderer) are not eligible for CPCE pilot grant consideration.
• Please submit the proposal as a single word document via email to Linda Scott, Sponsored Projects Officer, at scottl@email.chop.edu no later than 4:00 p.m. on the deadline date.

For a submission template, please click here.

Review Process and Selection Criteria

As detailed above, the review process will consist of two rounds. Applications meeting the definitions (above) for pilot clinical effectiveness research studies, and judged by the Pilot Grant Steering Committee to be of sufficient quality for further review, will be assigned to a reviewer, critiqued and scored. Reviewers will meet in a study section to discuss the merits and limitations of the competing proposals and to determine the awardee(s). All applicants whose proposals qualify for round two will receive a copy of reviewers' comments and score. Those applications that do not qualify for round two will be returned to the applicant without further review, critique or score.

The following criteria will be used to score the proposals. They are adapted from NIH Study Section Criteria.

• Significance of Study: Does the project address an important problem or a critical barrier to progress in the field?
• Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented?
• Likelihood of Impact of Clinical Effectiveness: If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
• Appropriateness of Budget: Is the proposed budget and period of support appropriate in relation to the proposed research?
• Likelihood of Future Research: If the aims of the project are achieved, will the results lend themselves to future research?
• Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

The above criteria will be scored on a scale from 1 (high impact) – 9 (low impact).

Common Pitfalls of Past CPCE Pilot Grant Applications:

1. Failure to anticipate difficulties or address limitations
2. Uncertainty regarding future direction or funding
3. Incomplete significance section; failure to adequately describe rationale
4. Overambitious for pilot study; unrealistic timeline
5. (Budget) Underestimate of biostatistical support needed to complete aims

Although projects may be funded up to a maximum of $10,000 priority will be given to those projects that include a prudent spending plan. CPCE will attempt to fund all requested budgets in full, but may elect to partially fund certain protocols in order to increase the number of funded proposals.

Reports:

• Principal investigators must submit a report at the end of the grant period for review by the Pilot Grant Program steering committee. The reports should include progress, expenditures and plans for disseminating results. Subsequent reports will be requested to include publications and extramural funding resulting from the research.
• Funds unspent at the end of the one-year grant period will be returned to CPCE. However, requests for rollover of funds for an additional year will be considered with adequate justification. We are very excited about the opportunity to support fellows and junior faculty who are interested in advancing CPCE's goals.

Questions?

Contact Megan Foley at foleym@email.chop.edu with any questions about the CPCE Pilot Grant Program. The Office of Sponsored Projects will coordinate the submission process; questions regarding this process can be directed to Linda Scott at scottl@email.chop.edu.

The Healthcare Analytics Unit (HAU) is a service unit of two centers at CHOP: CPCE and The Policy Lab. Visit the Policy Lab website at: http://policylab.us/index.php

The HAU:

• Serves as a resource for investigators who want to use administrative or other existing data to answer research questions;
• Offers programmer/analysts services to pull, clean, manage, model and analyze data;
• Provides expertise of center faculty members with advanced training in clinical epidemiology and public health.

Examples of databases to which the HAU provides access and expertise:

• Pediatric Health Information System (PHIS)
• Kids' Inpatient Database (KID)
• Medicaid
• NAMCS (National Ambulatory Medical Care Survey)
• NHDS (National Hospital Discharge Survey)
• Premier Perspective Database

To see samples of articles published using PHIS data, click here

To see samples of poster presentations using PHIS data, click here

For PHIS Data Use Forms, click here

HAU Staff

Xianqun Luan MS, Director
3535 Market Street, Rm 1545
267-426-8729
luan_AT_email.chop.edu

Mr. Luan has expertise in clinical trial studies (Phase I-III), biomedical research, and outcomes research. As a biostatistician, he has experience in clinical trial design and analysis, sample size estimation, implementation of statistical methods, statistical modeling for longitudinal, categorical, time to event and outcome data, and analysis of measurement agreement. Mr. Luan has extensive experience in statistical programming, statistical graphics, and statistical report presentation (SAS, Splus, and R). He has comprehensive knowledge about utilization and analysis of regional and national survey datasets, and he has strong database (Oracle, SQL server, Access, Filemaker, and Excel) integration, research data modeling, and analysis data generation skills.

Dingwei Dai, MSc, PhD, Programmer/Analyst
3535 Market Street, Rm 1544
267-426-5485
daid_AT_email.chop.edu

Dr. Dai has expertise in healthcare database management and data analysis, statistical modeling, clinical epidemiology, and health outcomes research. His skills include statistical programming (SAS, SQL, Matlab, SPSS), data linkage, data sampling, propensity score matching, and statistical methods in epidemiology. Dr. Dai has extensive experiences with large medical, pharmacy, and patient registries; national health surveys; and clinical trials databases.

Vera Huang, MS, Programmer/Analyst
3535 Market Street, Suite 1536
267-426-7748
huangys_AT_email.chop.edu

Ms. Huang has expertise in statistical design/analysis, structural equation modeling, multivariate regression, and sampling methodologies. She is skilled with PC SAS, Unix SAS, PC SPSS, and SQL. Ms. Huang has extensive knowledge of PHIS, Medicaid, and NSCAW databases.

Lihai Song, MS, Programmer/Analyst
3535 Market Street, Rm 1536
267-426-2885
songL_AT_email.chop.edu

Mr. Song has expertise in statistical modeling, experimental design, and analysis of large databases. He is skilled in designing, developing, and testing applications. As an SAS Certified Advanced Programmer, Mr. Song is experienced developing reports and models using SAS (SAS/BASE, SAS/ACCESS, SAS/MACRO, SAS/STAT, SAS/GRAPH). He has expertise with programming for clinical trials and for biological, pharmaceutical, and healthcare industries.

Requesting Data Services from the HAU

Complete and submit the HAU Data Services Request Form
We will contact you to schedule an appointment to discuss your project's feasibility and cost.

IRB APPROVAL FOR STUDIES THAT UTILIZE HAU SERVICES

The IRB has increasingly judged large datasets, such as those obtained from PHIS, to contain data that is not readily identifiable and therefore, outside the requirements for prospective IRB review and approval. Regulatory statements have made clear that "readily identifiable" does not mean possibly or potentially identifiable. This lowers the barriers for receipt and use of these datasets.

HIPAA does apply to the receipt/use of these datasets.
- If the dataset is a limited dataset, then all that is required to obtain and use it would be a data use agreement (no IRB approval required) with the data source (e.g. CHCA for PHIS data).

For research that utilizes datasets containing identifiable PHI, or for which data will be prospectively collected, IRB review/approval will continue to be needed.

It is the responsibility of the investigator to obtain IRB review and approval for those studies that require it, and to complete any data use agreements required by the data source.

For more complete information regarding what must be reviewed by the IRB, the use of registries/repositories for research, and other related topics, please see these sections of the research intranet site (authentication may be required):

https://intranet.research.chop.edu/pages/viewpage.action?pageId=25854699

https://intranet.research.chop.edu/pages/viewpage.action?pageId=29427527

https://intranet.research.chop.edu/pages/viewpage.action?pageId=26477172

https://intranet.research.chop.edu/display/cmtirb/Sharing+Data

SUBMITTING MANUSCRIPTS BASED ON RESEARCH UTILIZING DE-IDENTIFIED OR LIMITED DATASETS

When submitting a manuscript for publication, for a study that utilized PHIS or a comparable large and not readily identifiable dataset, and which therefore did not require IRB review/approval, the following boilerplate text can be used when needed during the journal's submission process. There are two versions, please choose the appropriate one, depending on the nature of your dataset.

1) In accordance with the Common Rule (45 CFR 46.102(f)) and the policies of the The Children's Hospital of Philadelphia IRB, this research, which utilized a de-identified dataset, was determined to not meet the definition of human subjects research.

2) In accordance with the Common Rule (45 CFR 46.102(f)) and the policies of the The Children's Hospital of Philadelphia IRB, this research, which utilized a limited dataset according to the terms of a valid data use agreement, was determined to not meet the definition of human subjects research.

HAU Tools

Sample Table To help define your population and measures, inclusion/exclusion criteria, etc

ICD 9 codes -- Use ICD 9 codes in your table to define population of interest

CTC codes (©2008 Thomson Healthcare) please use the appropriate PDF from the list below:

1. Pharmacy
2. Medical Supplies
3. Laboratory Services
4. Imaging Services
5. Clinical Services
6. Other Transacted Services

Questions?

CPCE Grants Database

In order to further support our goal of facilitating the performance of clinical research at CHOP, CPCE aims to support researchers in their grant writing endeavors by providing good examples of successfully funded grants. These samples help all to benefit from good ideas about grant formatting, methods, content and organization. We have created a central repository of grants by and for center members. The searchable listing is categorized and includes a complete document library for each grant.

Access to the Grants Database

Faculty who are center members and have a USER ID and password can click here to access the CPCE grants database.

Center members who do not have a USER ID/password for the database can request one by emailing hillman@email.chop.edu.

Those interested in becoming center members can also contact hillman@email.chop.edu.

Contribute to the Grants Database

We hope you will find this to be a useful tool. If so, we would greatly appreciate if you can support it by contributing one or more of your grants. This will give CPCE members a greater variety of examples of successfully funded grants. To submit a grant for uploading, simply e-mail the grant (no need to include the budget or budget justification) to center manager, Deb Hillman at: hillman@email.chop.edu.

Word documents are preferred, but other formats (e.g. pdfs) are also accepted.

Center for Simulation, Advanced Education and Innovation

CPCE members utilize the resources provided by The Center for Simulation, Advanced Education and Innovation at CHOP, which operates within the division of Anesthesiology and Critical Care Medicine. The Center facilitates the translation of scientific discoveries into practical implementation for both research and clinical care. The center is directed by Vinay Nadkarni, MD, and Evelyn Lengetti, RN, MSN., and is administered by Stephanie Tuttle, MBA.

Centralized classroom and skills lab training, satellite skills labs, and unit-based "virtual" lab exercises adjacent to patient care settings are routinely conducted. More than 250 teaching sessions are offered with at least 4,500 attendees, including:

• education encompassing recognition of shock and/or cardiac/respiratory failure
• vascular access, chest tube care and hemodynamic monitoring
• advanced and difficult airway assessment and intervention
• pacemaker evaluation
• EKG interpretation
• critical incident debriefing
• crew resource management

The education scope is expanding and includes basic and advanced life support training, simulation "boot camps" for orientation and training. This Center is supported by CHOP, and additional funding is supplemented with a federal Agency for Healthcare Research Quality (AHRQ) grant to study "training to excellence" using "just-in-time" and "just-in-place" simulation resuscitation education techniques for sharp end providers. The center staff includes multidisciplinary center directors, full-time administrative staff, a full-time clinical educator, as well as additional volunteer faculty (e.g. physicians, nurse, therapists, educators) to conduct training. The center also has non-overlapping research coordinator and research assistant support through funding from the AHRQ and Laerdal Foundation for Acute Medicine.

The is equipped with more than $500,000 of equipment in the form of:

• flat screen simulators
• virtual reality technology
• simulation mannequins with software
• task trainers
• defibrillators
• video monitoring and programming equipment
• 10-12 PCs and monitors
• a network server with secure storage
• video editing hardware and software
• disposable supplies

In addition, there are collaborative links with the 7,000 square foot Brunner Technology Center at the Penn School of Nursing, which trains more than 8,000 simulation encounters annually, and the Measey Medical Simulation Center at the Penn School of Medicine. Both of these centers provide adjunctive expertise, equipment and personnel to accomplish training and research objectives. These resources have been mobilized and committed to support the evolving Laerdal-funded CHOP Center of Excellence for Resuscitation Research.