KHI Cardiovascular Trials Project Survey for Stakeholders

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

Question Title

* 1. Which stakeholder group do you represent?

Academic researcher

Academic research organization

Clinician

Sponsor/Pharmaceutical/Device Company

Contract research organization

Regulatory

Other (please specify)

Question Title

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

Cardiology

Nephrology

Endocrinology

Pediatric Cardiology

Pediatric Nephrology

Pediatric Endocrinology

Other (please specify)

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

Question Title

* 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)

Other challenges (Please elaborate on any of the above selections and/or provide a different challenge.)

Question Title

* 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

Question Title

* 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)

Other solutions (Please elaborate on any of the above selections and/or provide a different solution)

Question Title

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

Follow-up

Question Title

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

Yes

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

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

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