Clinical Trials in Nephrology

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Clinical Trials in Nephrology

• Baxter Experience

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Clinical trials in specialties of Internal
Medicine
Figure 1. Number of randomized controlled trials
(RCT) published in nephrology and 12 other
specialties of internal medicine from 1966 to
2002. (Strippoli et al)
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PD Clinical Evidence Gaps (KDOQI)

• Randomized, controlled trials on PD adequacy and
  optimal dose targets
• Prospective, randomized trials have been
  short-term
• Little information on long-term complications
• Data predominantly derived from patients on PD in
  Mexico Hong Kong
• Lack of randomized, controlled trials in APD
• Clinical Importance of small molecule/middle
  molecule clearance
• Paucity of data in children

KDOQ1, 2006
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Challenges

• Clinical
• Regulatory
• Logistical

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Clinical Challenges

• Difficulty in randomization for important
  questions
• NECOSAD group
• Reluctance to conduct studies outside of DOQ1
  guidelines
• ADEMEX Trial
• Meaningful and validated endpoints
• Icodextrin trials (Ultrafiltration)
• NIH funding v. pharma funding
• Future of academic institutions and physicians
  based on NIH funding
• Availability some patient groups
• PD penetration in the US 9
• Patients are being treated in different dialysis
  chains
• Long-term follow-up (drop-out and death rates)
• Patient recruitment/compensation

6
Regulatory Challenges

• PD Solutions unavailable in some regions
• Physioneal/Nutrineal
• Endpoints acceptable to regulatory authorities
• UF
• Biochemical Markers/No validated surrogate
  markers

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Logistical Challenges

• Clinicians not trained to conduct clinical trials
  
• Repetitive involvement of Investigators
• Sample size
• Peritonitis
• Preservation of peritoneal membrane function
• Cost (Pharmaceutical trials/Regulatory
  environment)
• Investigator grants
• CRO
• Monitoring
• Inconsistencies in lab methods
• Overhead costs
• Patients/Dialysis center

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Randomized Clinical TrialsCompleted by Baxter
(100 pts.)
Trial
Trial
Location
No. pts.
Physioneal ADEMEX Extraneal Extraneal Extraneal
HTT Extraneal Registry Epomax Epomax
106 965 175 287 92 750 107 107
1996-1997 1998- 2001 1998-1998 1998-1999 2001-200
3 -2005 2003-2004 2004-2005
EU Mexico US, Canada US, Canada US,
Australia EU Eastern EU Eastern EU
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What Can We Do to Improve This Situation?

• Continue to conduct randomized, controlled trials
  outside the US
• Enhance prestige of corporate funding
• Prepare and train physicians/staff to do clinical
  trials
• Transparency of data register trials in Clinical
  Trials. gov.
• Joint lobbying to NIH and potentially to Health
  Authorities
• Regulatory approval of products used in ROW
• ASN, pharma and academics can partner to conduct
  registry type studies
• Understand what needs to be in place to do
  studies in the US

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Evidence Based Medicine
Pharma
Health Authorities
Patient
Academia