KHI Cardiovascular Trials Survey

Kidney disease is highly prevalent among patients with cardiovascular disease and is associated with worse cardiovascular outcomes. Thus, the management of cardiovascular disease in patients with kidney disease is a common and important clinical problem. However, the evidence on which to base the optimal management of cardiovascular disease in patients with advanced chronic kidney disease (CKD) (i.e., estimated glomerular filtration rate <30 ml/min/1.73 m2) not requiring dialysis and end-stage renal disease (ESRD) requiring dialysis is limited by their exclusion from cardiovascular trials performed in the general population and challenges with conducting dedicated trials in these populations.

We are conducting a survey to understand the challenges with involving patients with advanced CKD not requiring dialysis and ESRD requiring dialysis in cardiovascular clinical trials and to generate solutions to overcome these challenges.  We are defining cardiovascular clinical trials as studies of drugs such as (though not limited to) antiplatelet and anticoagulant agents, or heart failure treatments; procedures such as percutaneous coronary intervention; and devices such as a wearable cardioverter defibrillator.

Your responses will be anonymous. Thank you for your participation.

Stakeholder Background

* 1. Which stakeholder group do you represent?

* 2. What are the specialty(ies) or therapeutic area(s) in which you work? Check all that apply.

Challenges with Involving Patients with Advanced Chronic Kidney Disease Not Requiring Dialysis and End-Stage Renal Disease Requiring Dialysis in Cardiovascular Clinical Trials

* 3. What are the challenges with a) involving patients with advanced chronic kidney disease (CKD) (i.e., estimated glomerular filtration rate <30 ml/min/1.73 m2) not requiring dialysis and/or end-stage renal disease (ESRD) requiring dialysis in cardiovascular clinical trials? Check all that apply and specify the patient population for which the challenge is relevant. If a challenge is not listed here, please elaborate in the section labeled "Other". 

(Abbreviations: CKD = chronic kidney disease, eGFR = estimated glomerular filtration rate, ESRD = end-stage renal disease)

  Advanced CKD (eGFR <30 ml/min/1.73 m2) Not Requiring Dialysis ESRD Requiring Dialysis 
a. Low prevalence of patients with advanced CKD and/or ESRD
b. Lack of efficacy or smaller treatment effect that could weaken overall treatment effect
c. Safety concerns  
     i. Concern for higher risk of adverse events
    ii. Concern that intervention could worsen kidney disease
    iii. Concern that intervention could worsen cardiovascular disease
d. Protocol design
    i. Standard protocols exclude patients with advanced CKD and/or ESRD
    ii. Uncertainty about effect of renal impairment on drug exposure and proper drug dosing
    iii. Lack of standardized cardiovascular endpoints specific to patients with advanced CKD and/or ESRD
    iv. Lack of validated surrogate cardiovascular endpoints specific to patients with advanced CKD and/or ESRD
e. Financial concerns
     i. Need for additional funds or resources to monitor patients at high risk for adverse events
    ii. Financial costs of accessing patients
    iii. Risk of poor formulary placement if trial only enrolls specific populations
    iv. Poor reimbursement by payers, even after drug approval
    v. Reluctance of senior management to support development
f. Regulatory barriers
    i. Potential regulatory risk (e.g., safety data could impact label or approval)
    ii. Lack of regulatory incentives (e.g., waiver of application fees, market exclusivity)
g. Patient recruitment  
    i. Patient exclusion based on multiple comorbidities
    ii. Low patient awareness of clinical trial availability 
    iii. Patient reluctance to participate in clinical trials
    iv. Low physician awareness of clinical trial availability
     v. Physician reluctance to participate in clinical trials or registries
    vi. Physician reluctance to enroll patients
    vii. Lack of physician experience with clinical trial conduct

* 4. Of the choices you selected, what is the most significant challenge? Please explain briefly.

Solutions to Overcoming the Challenges with Involving Patients with Advanced Chronic Kidney Disease Not Requiring Dialysis and End-Stage Renal Disease Requiring Dialysis in Cardiovascular Clinical Trials

* 5. What are the potential solutions to overcome challenges with involving patients with advanced chronic kidney disease (CKD) (i.e., estimated glomerular filtration rate <30 ml/min/1.73 m2) not requiring dialysis and/or end-stage renal disease (ESRD) requiring dialysis in cardiovascular clinical trials? Check all that apply and specify the patient population for which the solution is relevant. If a solution is not listed here, please elaborate in the section labeled "Other". 

(Abbreviations: CKD = chronic kidney disease, eGFR = estimated glomerular filtration rate, ESRD= end-stage renal disease)

  Advanced CKD (eGFR <30 ml/min/1.73 m2) Not Requiring Dialysis ESRD Requiring Dialysis 
a. Trial design improvements
    i. Use of historical controls
    ii. Randomized registries of patients with advanced CKD and/or ESRD running in parallel to the main trial
    iii. Standardized cardiovascular endpoints specific to patients with CKD and/or ESRD
    iv. Validated surrogate cardiovascular endpoints specific to patients with CKD and/or ESRD
    v. Early engagement with patients in the design of the trial (e.g., including patients on steering committees)
b. Risk mitigation methods
    i. Use of predictive biomarkers for adverse events
c. Regulatory solutions
     i. Waiver of application fees as a regulatory incentive
    ii. Market exclusivity to sponsors who conduct dedicated trials for patients with advanced CKD and/or ESRD as a regulatory incentive
    iii. Close collaboration with regulators to better define endpoints and trial design prior to study initiation
d. Financial incentives
    i. Building of a business case such that the return-on-investment can be better appreciated
    ii. Reimbursement policy changes
e. Patient recruitment improvements
    i. Investigator-run trial network for patient recruitment
    ii. Acknowledgement and communication of mortality and/or morbidity of advanced CKD and ESRD to patients
    iii. Cultural shift encouraging patients with advanced CKD and/or ESRD to enroll in clinical trials
    iv. Communication of benefits of trial participation by other patients or kidney patient advocacy group
f. Closer collaboration with community-based researchers regarding clinical trial design, conduct, analysis, and recruitment

* 6. Of the choices you selected, what do you believe will be the most effective? Please explain briefly.

Follow-up

* 7. Would you be willing to participate in a focus group or individual interview to discuss your perspective further?

If yes, contact the Kidney Health Initiative at khi@asn-online.org or (202) 618-6985.

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