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Toward Building Better Biomarkers Statistical Methodology

12/2/2014 8:00 AM
12/2/2014 6:15 PM
No
No

​For questions concerning program content, contact:

Paul L Kimmel, MD, MACP, FASN
DKUHD NIDDK
Two Democracy Plaza, NIDDK NIH Room 611
Bethesda, MD 20892
Phone: (301) 594-1409
Email: KimmelP@extra.niddk.nih.gov

For questions concerning meeting logistics, contact:

David Henson
The Scientific Consulting Group, Inc.
656 Quince Orchard Road, Suite 210
Gaithersburg, MD  20878
Phone:  (301) 670-4990
Fax:  (301) 670-3815
Email: dhenson@scgcorp.com

 

Event Details

Clinical considerations

There is concern regarding  the clinical  utility of biomarkers in kidney disease (Acute Kidney Injury [AKI], Chronic Kidney Disease [CKD], various forms of glomerulonephritis [GN], and polycystic kidney disease [PKD]) for prediction of diverse clinical outcomes (such as  loss of renal function, development of cardiovascular disease, diminution of quality of life, death), as well as  in drug development (for refinement of risk stratification or drug response). There is dissatisfaction with the results of published  biomarker  studies  and the  lack of uptake of biomarkers in clinical practice in patients with kidney disease. Finally, we don’t know the answers to several key questions. Some of these are listed below.

Of what use is this biomarker to me or my patient in the clinic?

Has “context of use” or “fit purpose” been  identified, or  do the present studies evaluate biomarkers on convenience samples?

How can we deal with the paradox of well-established but crude measures which biomarkers must enhance?

Can we  develop markers for kidney disease  that are superior to   S[Cr] and proteinuria?

Does the  Framingham  study provide a better framework  for the evaluation of biomarkers – or do biomarker studies have to be designed de novo for each context?

How does biomarker science allow us to move from a population focus to individual considerations:  the patient and the physician in the consultation room (or at the bedside) --  considering a distinct outcome?

Can we as biomarker scientists develop physician / patient perspectives - assessing risk for the individual, or outcome for the individual with drug therapy?

Statistical Considerations

Have we developed a true set of  biomarker statistical analyses? Or are we fitting old techniques to new contexts / issues?  What does a biomarker showing independent association with a distant outcome in a Cox regression mean? What are the key elements of design for a meaningful biomarker study?   What metrics are appropriate for assessing incremental value of biomarkers?

What does “prediction” mean?

Is “prediction” different for present measures (eg eGFR) compared to future outcomes (risk of future decrement in renal function, need for ESRD treatment, or death)?

How can we  make  predictive models in kidney disease patients more precise?

Can causal links between biomarker levels or changes identified by present statistical methods be strengthened?

This workshop will grapple with these thorny questions.  Breakout groups, composed of biostatisticians and clinical nephrologists,  will consider the issues and put forth approaches for moving forward.  

Agenda

AGENDA

Tuesday, December 2, 2014

 

8:00 a.m.      Introduction P. Kimmel & R. Star
 
8:10 a.m.Biomarkers, Clinical and Research Utility: Current State of the Art      
(10 min followed by 15 min Q/A) Moderators:  H. Rodriguez, J. Lachin

Why we need kidney biomarkers for prognosis and diagnosis C.-Y.  Hsu

Review of current methods to assess the prognostic/diagnostic value of kidney biomarkers C. Parikh

What not to do when evaluating the prognostic/diagnostic value of biomarkers F. Harrell

9:25 a.m.      Break

9:45 a.m.      Towards better interpretation of prognostic/diagnostic value of biomarkers
(10 min followed by 15 min Q/A) Moderators: A. Thompson, M.J. Pencina

Clinical perspective – What do we need? R.S. Vasan

Regulatory needs regarding biomarkers and drug development tools M. Walton

Statistical perspective – What is the state of the art? R. D'Agostino

Applied perspective – How are biomarkers used in practice and in research? M. Gail

Decision analysis – Hope or myth? E. Steyerberg

11:50 a.m.    Lunch
12:20 p.m. New Frontiers -- Novel ways to look at/for biomarkers  
(10 min followed by 15 min Q/A) Moderators: K. Lemley, M.J. Pencina
                  Selection methods K. Kerr

Prognostic models of the future A. Foulkes

Use of biomarkers in combinations to enhance accuracy and clinical utility R. Pfeiffer

Use of biomarkers – Longitudinal measurement models V. Chinchilli

Combining cohorts and creating valid metanalyses J. Coresh

2:25 p.m.     Break

 2:45 p.m.    Breakout Sessions – 4 Groups:

  1. Models with biomarkers
  2. Assessment of added value of biomarkers
  3. Strategies and knowledge from combining existing studies/cohorts?
  4. Combining Biomarkers

 4:45 p.m.    Break

 5:00 p.m.   Breakout Reports (15 min/each, including discussion)
 
 6:00 p.m.    Summary & Closing Remarks P. Kimmel & R. Star

 6:15 p.m.    Adjourn

Breakout Groups

Overarching Question/Objective for All Groups

What are the key methodological advances needed for enhance biomarker research?

Group 1
Foulkes /Parikh

 

Models with biomarkers

  • Better methods to construct risk prediction models
  • Selection of cut-offs for biomarkers
  • Multi-level outcomes for AKI and CKD
  • Mediation analysis for prognostic model

Group 2
Cook/Lemley

Assessment of added value of biomarkers

  • Statistical metrics and data summaries for model improvement with biomarkers
  • Cost-effectiveness and cost-benefit analysis
  • Cross-validation and external validation of biomarker results

Group 3
Coresh/ Gimmoty/Hsu

Strategies and knowledge from combining existing studies/cohorts?

  • Meta-analysis—study level vs. patient level
  • Different assays, clinical settings, cohorts
  • Center effects in multicenter biomarker studies
  • Combining performance metrics
  • Data sharing  considerations

Group 4
Song/Feldman

Combining Biomarkers

  • Correlation, biology or outcome-driven combinations
  • Developing guidelines for combinations
  • Which metrics to focus on in combination
  • Longitudinal combination of biomarkers

Directions/Travel

Toward Building Better Biomarkers Statistical Methodology

December 2, 2014

MEETING FACILITY

National Institutes of Health Campus

Natcher Building (Room F1/F2)
45 Center Drive, Building 45

Bethesda, MD  20892

HOTEL ACCOMMODATIONS

Hyatt Regency Bethesda
One Bethesda Metro Center

Bethesda, MD  20814
Telephone: 301-657-1234
http://www.bethesda.hyatt.com/en/hotel/home.html

Sleeping Room Rate: $177 per night, plus 13% tax
Check-In Time: 4:00 p.m.
Check-Out Time: 11:00 a.m.

Parking: Self-parking at the hotel is $12 per day and $20 overnight.

A block of sleeping rooms has been reserved at the Hyatt Regency Bethesda, Maryland, for arrival on Monday, December 1, 2014, and departure on Tuesday, December 2, 2014. The room rate is $177, plus 13% tax per night.

Please contact the Hyatt Regency Bethesda by Thursday, October 30, 2014, at (301) 657-1234 and reference the Toward Building Better Biomarkers Meeting rooming block when making your sleeping room reservations.

You will be responsible for the room cost and your incidental charges upon check-out. You will be reimbursed after the meeting for the cost of the room and taxes. After October 30, 2014, the hotel will accept reservations on a space-available basis at the prevailing hotel rate.

When making a reservation, please provide your room and bedding preferences. The hotel will assign specific room types at check-in, based on availability. Please be advised that requests are not guaranteed.

If for any reason you need to cancel your hotel reservation, please do so 24 hours in advance of your check-in date.

 

DIRECTIONS TO THE HYATT REGENCY BETHESDA

From Points North:

From points North and East: Take I-95 South to I-495 (Capital Beltway) West toward Silver Spring. Take Exit 34 (Wisconsin Avenue/Route 355). Follow Route 355 South for approximately 3 miles and the Hyatt Regency Bethesda will be on the right, on the corner of Wisconsin Avenue and Old Georgetown Road.

From points North and West: Take I-270 South to I-495 (Capital Beltway) East toward Washington, D.C. Stay in one of the three left lanes. Follow signs for 355 South, a left-lane exit, onto Wisconsin Avenue. Follow Route 355 South for approximately 3 miles and the Hyatt Regency Bethesda will be on the right, on the corner of Wisconsin Avenue and Old Georgetown Road.

From Points South:

Take I-95 North to I-495 (Capital Beltway) toward Tysons Corner/Rockville.
Follow I-495 for 20 miles. At the I-495/I-270 split, stay to the right on I-495. Take Exit 34 (Wisconsin Avenue/Route 355). Follow Route 355 South for approximately 3 miles and the Hyatt Regency Bethesda will be on the right, on the corner of Wisconsin Avenue and Old Georgetown Road.

From Baltimore/Washington International Airport (BWI):

Take Route 195 West to Exit 4 (I-95 South). From I-95 take I-495 (Capital Beltway) West toward Silver Spring. Take Exit 34 (Wisconsin Avenue/Route 355). Follow Route 355 South for approximately 3 miles and the Hyatt Regency Bethesda will be on the right, on the corner of Wisconsin Avenue and Old Georgetown Road.

From Washington Dulles International Airport (IAD):

Take the Dulles Access Road for approximately 13 miles to Exit 18. Move to the right on the Dulles Toll Road (Route 267); get off at Exit 18. Stay to the left on the ramp for Bethesda/Baltimore and proceed toward Bethesda on I-495 (Capital Beltway) for approximately 9 miles. At the I-495/I-270 split, stay to the right on I-495. Take Exit 34 (Wisconsin Avenue/Route 355 South). Follow Route 355 South for approximately 3 miles and the Hyatt Regency Bethesda will be on the right, on the corner of Wisconsin Avenue and Old Georgetown Road.

From Ronald Reagan National Airport (DCA):

Take the George Washington Parkway North to I-495 (Capital Beltway) and follow the signs to Maryland. At the I-495/I-270 split, stay to the right on I-495. Take Exit 34 (Wisconsin Avenue/Route 355). Follow Route 355 South for approximately 3 miles and the Hyatt Regency Bethesda will be on the right, on the corner of Wisconsin Avenue and Old Georgetown Road.

METRO
The Metro System is clean, reliable, and safe. It operates from 5:30 a.m. to 12:00 midnight, Monday through Thursday; 5:00 a.m. to 2:00 a.m. on Fridays; 8:00 a.m. to 2:00 a.m. on Saturdays; and 8:00 a.m. to 12:00 midnight on Sundays. Each passenger must buy a fare card to travel in the system. Guides for purchasing fare cards are posted on the vending machines in each station. Each Metro car features a complete color-coded map. Station attendants on duty at each station can provide additional information on request.
From Union Station or downtown Washington (main Metro Lines into the city converge at Metro Center Station and Gallery Place Station), take the Metro Red Line toward Shady Grove or Grosvenor. Exit at the Bethesda Metro Station. The Hyatt is directly above the Bethesda Metro Station.
TAXIS
The taxi fare is approximately $55 from Ronald Reagan Washington National Airport, approximately $65 from Washington Dulles International Airport, and approximately $90 from Baltimore/Washington International Thurgood Marshall Airport. Fares may differ during peak travel hours.

DIRECTIONS TO NIH CAMPUS


METRO
Metro service is available and is located directly below the Hyatt Regency Bethesda Hotel. Follow the signs to the metro rail system.  Once there, follow the signs and take the red line in the direction of Shady Grove.  Exit the train after one stop at the Medical Center Metro stop.  Follow signs to NIH and proceed through the Security Checkpoint.
TAXIS
Taxis are readily available most of the day.  You can catch a cab by exiting the Hyatt Regency Bethesda Hotel through the front doors.  Taxi fare is approximately $5–$10 and NIH is only a short distance away from the hotel.

Minutes

Attendees

Abstracts

Location

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Webinar

Contacts

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​For questions concerning program content, contact:

Paul L Kimmel, MD, MACP, FASN
DKUHD NIDDK
Two Democracy Plaza, NIDDK NIH Room 611
Bethesda, MD 20892
Phone: (301) 594-1409
Email: KimmelP@extra.niddk.nih.gov

For questions concerning meeting logistics, contact:

David Henson
The Scientific Consulting Group, Inc.
656 Quince Orchard Road, Suite 210
Gaithersburg, MD  20878
Phone:  (301) 670-4990
Fax:  (301) 670-3815
Email: dhenson@scgcorp.com