Kira Clark

All Publications

• Opportunities to Increase Science of Diversity and Inclusion in Clinical Trials: Equity and a Lack of a Control. Journal of the American Heart Association Igwe, J., Wangdak Yuthok, T. Y., Cruz, E., Mueller, A., Lan, R. H., Brown-Johnson, C., Idris, M., Rodriguez, F., Clark, K., Palaniappan, L., Echols, M., Wang, P., Onwuanyi, A., Pemu, P., Lewis, E. F. 2023: e030042

  Abstract

  The United States witnessed a nearly 4-fold increase in personal health care expenditures between 1980 and 2010. Despite innovations and obvious benefits to health, participants enrolled in clinical trials still do not accurately represent the racial and ethnic composition of patients nationally or globally. This lack of diversity in cohorts limits the generalizability and significance of results among all populations and has deep repercussions for patient equity. To advance diversity in clinical trials, robust evidence for the most effective strategies for recruitment of diverse participants is needed. A major limitation of previous literature on clinical trial diversity is the lack of control or comparator groups for different strategies. To date, interventions have focused primarily on (1) community-based interventions, (2) institutional practices, and (3) digital health systems. This review article outlines prior intervention strategies across these 3 categories and considers health policy and ethical incentives for substantiation before US Food and Drug Administration approval. There are no current studies that comprehensively compare these interventions against one another. The American Heart Association Strategically Focused Research Network on the Science of Diversity in Clinical Trials represents a multicenter, collaborative network between Stanford School of Medicine and Morehouse School of Medicine created to understand the barriers to diversity in clinical trials by contemporaneous head-to-head interventional strategies accessing digital, institutional, and community-based recruitment strategies to produce informed recruitment strategies targeted to improve underrepresented patient representation in clinical trials.

  View details for DOI 10.1161/JAHA.123.030042

  View details for PubMedID 38108253

• Who Are We Missing? Reporting of Transgender and Gender-Expansive Populations in Clinical Trials. Journal of the American Heart Association Rice, E. N., Lan, R. H., Nunes, J. C., Shah, R., Clark, K., Periyakoil, V. S., Chen, J. H., Lin, B., Echols, M., Awad, C., Idris, M. Y., Cruz, E. R., Poullos, P. D., Lewis, E. F., Brown-Johnson, C., Igwe, J., Shen, S., Palaniappan, L., Stefanick, M. L., Ritter, V., Pemu, P., Rodriguez, F., Deb, B., Pundi, K., Wang, P. J. 2023: e030209

  View details for DOI 10.1161/JAHA.123.030209

  View details for PubMedID 37947088

• Disabilities Reporting in Cardiac Clinical Trials: How Are We Doing? Journal of the American Heart Association Lan, R. H., Rice, E. N., Nunes, J. C., Shah, R., Igwe, J. K., Clark, K., Periyakoil, V. S., Chen, J. H., Lin, B., Awad, C., Idris, M., Cruz, E. R., Lewis, E. F., Johnson, C. B., Wang, P. J. 2023: e029726

  View details for DOI 10.1161/JAHA.123.029726

  View details for PubMedID 37949834

• Population Pharmacokinetics of Doxycycline in Children ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Thompson, E. J., Wu, H., Melloni, C., Balevic, S., Sullivan, J. E., Laughon, M., Clark, K. M., Kalra, R., Mendley, S., Payne, E. H., Erinjeri, J., Gelber, C. E., Harper, B., Cohen-Wolkowiez, M., Hornik, C. P., Benjamin, D. K., Hornik, C., Zimmerman, K., Kennel, P., Beci, R., Hornik, C., Kearns, G. L., Laughon, M., Paul, I. M., Sullivan, J., Wade, K., Delmore, P., Best Pharmaceuticals Children 2019; 63 (12)

  Abstract

  Doxycycline is a tetracycline-class antimicrobial labeled by the United States (U.S.) Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline class antibiotics and tooth staining, although doxycycline may be used off-label in severe conditions. Accordingly, there is a paucity of pharmacokinetic (PK) data to guide dosing in children 8 years and younger. We leveraged opportunistically-collected plasma samples after intravenous (IV) and oral doxycycline doses received per standard of care to characterize the PK of doxycycline in children of different ages, and evaluated the effect of obesity and fasting status on PK parameters.We developed a population PK model of doxycycline using data collected from 47 patients 0-18 years of age, including 14 participants ≤8 years. We developed a 1 compartment PK model and found doxycycline clearance to be 3.32 L/h/70 kg and volume to be 96.8 L/70kg for all patients; comparable to values reported in adults. We estimated a bioavailability of 89.6%, also consistent with adult data. Allometrically scaled clearance and volume of distribution did not differ between children 2 to ≤8 years of age and children >8 to ≤18 years of age, suggesting that younger children may be given the same per kg dosing. Obese and fasting status were not selected for inclusion in the final model. Additional doxycycline PK samples collected in future studies may be used to improve model performance and maximize its clinical value.

  View details for DOI 10.1128/AAC.01508-19

  View details for Web of Science ID 000497999100056

  View details for PubMedID 31548185

  View details for PubMedCentralID PMC6879254

• Health-related quality of life in glomerular disease KIDNEY INTERNATIONAL Canetta, P. A., Troost, J. P., Mahoney, S., Kogon, A. J., Carlozzi, N., Bartosh, S. M., Cai, Y., Davis, T., Fernandez, H., Fornoni, A., Gbadegesin, R. A., Herreshoff, E., Mahan, J. D., Nachman, P. H., Selewski, D. T., Sethna, C. B., Srivastava, T., Tuttle, K. R., Wang, C., Falk, R. J., Gharavi, A. G., Gillespie, B. W., Greenbaum, L. A., Holzman, L. B., Kretzler, M., Robinson, B. M., Smoyer, W. E., Guay-Woodford, L. M., Reeve, B., Gipson, D. S., Ahn, W., Appel, G. B., Babayev, R., Batal, I., Bomback, A. S., Brown, E., Campenot, E. S., Canetta, P., Carlassara, L., Chan, B., Chatterjee, D., D'Agati, V. D., Delbarba, E., Dogra, S., Foroncewicz, B., Ghiggeri, G., Hines, W. H., Husain, S., Jain, N. G., Khairallah, P., Kil, B., Kiryluk, K., Jeyabalan, A., Lau, W. L., Lin, F., Lugani, F., Marasa, M., Markowitz, G., Mohan, S., Mu, X., Mucha, K., Nickolas, T. L., Piva, S., Radhakrishnan, J., Rao, M. K., Renu, R., Sanna-Cherchi, S., Santoriello, D., Shirazian, S., Stokes, M. B., Uy, N., Valeri, A. M., Al-Uzri, A., Ambruzs, J., Ashoor, I., Aviles, D., Baracco, R., Barcia, J., Bartosh, S., Belsha, C., Bowers, C., Braun, M. C., Chernitskiy, V., Chishti, A., Claes, D., Clark, K., Cramer, C., Davis, K., Erkan, E., Feig, D., Freundlich, M., Gaut, J., Gbadegesin, R., Hanna, M., Hidalgo, G., Hooper, D., Hunley, T. E., Jain, A., Kallash, M., Kamel, M., Khalid, M., Klein, J. B., Kump, T., Lane, J. C., Liapis, H., Mahan, J., Mathews, N., Nester, C., Pan, C., Patterson, L., Patel, H., Raad, A., Revell, A., Rheault, M. N., Silva, C., Sreedharan, R., Steinke, J., Sumner, S., Twombley, K., Wenderfer, S. E., Vasylyeva, T. L., Weaver, D. J., Wong, C. S., Yin, H., Achanti, A., Almaani, S., Ayoub, I., Budisavljevic, M., D'Angelo, M., Fatima, H., Falk, R., Fogo, A., Gibson, K., Glenn, D., Hogan, S., Jennette, J., Julian, B., Kidd, J., Laurin, L., Massey, H., Mottl, A., Murphy, S., Nachman, P., Nadasdy, T., Novak, J., Parikh, S., Poulton, C., Powell, T., Renfrow, M., Reynolds, M., Rizk, D., Rovin, B., Royal, V., Sanghani, N., Self, S., Adler, S., Alachkar, N., Alpers, C., Matar, R., Avila-Casado, C., Bagnasco, S., Brede, E., Brown, E., Cattran, D., Choi, M., Dell, K. M., Dewalt, D., Denburg, M., Dukkipati, R., Fervenza, F. C., Gadegbeku, C., Gipson, P., Gonzalez-Zea, A., Hasely, L., Hendren, E., Hingorani, S., Hladunewich, M., Hogan, J., Hou, J., Jefferson, J., Jhaveri, K., Johnstone, D. B., Kaskel, F., Kogan, A., Kopp, J., Lafayette, R., Lemley, K., Malaga-Dieguez, L., Meyers, K., Neu, A., O'Shaughnessy, M., O'Toole, J. F., Oliverio, A., Palmer, M., Parekh, R., Pitter, R., Reich, H., Reidy, K., Rondon, H., Sambandam, K. K., Sampson, M., Sedor, J. R., Schelling, J., Sperati, J. C., Swiatecka-Urban, A., Trachtman, H., Waldman, M., Weisstuch, J., Wiggins, R., Williams, D., Winkler, C., Vento, S., Young, E., Zhdanova, O., Barisoni, L., Beil, C., Eikstadt, R., Gillespie, B., Graff, J., Hewitt, S., Hill-Callahan, P., Helmuth, M., Lienczewski, C., Mansfield, S., Mariani, L., McCullough, K., Moore, N., Nast, C. C., Sexton, M., Troost, J., Wladkowski, M., Zee, J., Zinsser, D., CureGN Consortium 2019; 95 (5): 1209–24

  Abstract

  There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables.

  View details for DOI 10.1016/j.kint.2018.12.018

  View details for Web of Science ID 000465213400024

  View details for PubMedID 30898342

• CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease AMERICAN JOURNAL OF KIDNEY DISEASES Mariani, L. H., Bomback, A. S., Canetta, P. A., Flessner, M. F., Helmuth, M., Hladunewich, M. A., Hogan, J. J., Kiryluk, K., Nachman, P. H., Nast, C. C., Rheault, M. N., Rizk, D., Trachtman, H., Wenderfer, S. E., Bowers, C., Hill-Callahan, P., Marasa, M., Poulton, C. J., Revell, A., Vento, S., Barisoni, L., Cattran, D., D'Agati, V., Jennette, J., Klein, J. B., Laurin, L., Twombley, K., Falk, R. J., Gharavi, A. G., Gillespie, B. W., Gipson, D. S., Greenbaum, L. A., Holzman, L. B., Kretzler, M., Robinson, B., Smoyer, W. E., Guay-Woodford, L. M., Ahn, W., Appel, G. B., Babayev, R., Batal, I., Brown, E., Campenot, E. S., Canetta, P., Carlassara, L., Chan, B., Chatterjee, D., D'Agati, V. D., Delbarba, E., Dogra, S., Fernandez, H., Foroncewicz, B., Ghiggeri, G., Hines, W. H., Husain, S., Jain, N. G., Khairallah, P., Kil, B., Jeyabalan, A., Lau, W. L., Lin, F., Lugani, F., Markowitz, G., Mohan, S., Mu, X., Mucha, K., Nickolas, T. L., Piva, S., Radhakrishnan, J., Rao, M. K., Regunathan-Shenk, R., Sanna-Cherchi, S., Santoriello, D., Shirazian, S., Stokes, M. B., Yu, N., Valeri, A. M., Zviti, R., Al-Uzri, A., Ambruzs, J., Ashoor, I., Aviles, D., Baracco, R., Barcia, J., Bartosh, S., Belsha, C., Braun, M. C., Cai, Y., Chernitskiy, V., Chishti, A., Claes, D., Clark, K., Cramer, C., Davis, K., Dutcher, A., Erkan, E., Feig, D., Freundlich, M., Gaut, J., Gbadegesin, R., Hanna, M., Hidalgo, G., Hooper, D., Hunley, T. E., Jain, A., Kallash, M., Kamel, M., Khalid, M., Kump, T., Lane, J. C., Liapis, H., Mahan, J., Mathews, N., Nester, C., Pan, C., Patterson, L., Patel, H., Raad, A., Silva, C., Sreedharan, R., Srivastava, T., Steinke, J., Sumner, S., Vasylyeva, T. L., Wang, C., Weaver, D. J., Wong, C. S., Yin, H., Achanti, A., Almaani, S., Ayoub, I., Budisavljevic, M., D'Angelo, M., Derebail, V., Fatima, H., Falk, R., Fogo, A., Gibson, K., Glenn, D., Hogan, S., Jain, K., Julian, B., Kidd, J., Massey, H., Mottl, A., Murphy, S., Nadasdy, T., Novak, J., Parikh, S., Poulton, C., Powell, T., Reeve, B., Renfrow, M., Reynolds, M., Rizk, D., Rovin, B., Royal, V., Saha, M., Sanghani, N., Self, S., Adler, S., Alachkar, N., Alpers, C., Matar, R., Avila-Casado, C., Bagnasco, S., Brede, E., Brown, E., Cattran, D., Choi, M., Contreras, G., Dell, K. M., Dewalt, D., Denburg, M., Dukkipati, R., Fervenza, F. C., Fornoni, A., Gadegbeku, C., Gipson, P., Gonzalez-Zea, A., Hasely, L., Hendren, E., Hingorani, S., Hladunewich, M., Hogan, J., Hou, J., Jefferson, J., Jhaveri, K., Johnstone, D. B., Kaskel, F., Kogan, A., Kopp, J., Lafayette, R., Lemley, K., Malaga-Dieguez, L., Meyers, K., Neu, A., O'Shaughnessy, M., O'Toole, J. F., Oliverio, A., Palmer, M., Parekh, R., Pitter, R., Reich, H., Reidy, K., Rondon, H., Sambandam, K. K., Sampson, M., Sedor, J. R., Selewski, D. T., Sethna, C. B., Schelling, J., Sperati, J. C., Swiatecka-Urban, A., Tuttle, K. R., Waldman, M., Weisstuch, J., Wiggins, R., Williams, D., Winkler, C., Young, E., Zhdanova, O., Beil, C., Eikstadt, R., Gillespie, B., Graff, J., Hewitt, S., Herreshoff, E., Lienczewski, C., Mansfield, S., Mariani, L., McCullough, K., Moore, N., Robinson, B. M., Sexton, M., Troost, J., Wladkowski, M., Zee, J., Zinsser, D., CureGN Consortium 2019; 73 (2): 218–29

  Abstract

  Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death.Multicenter prospective cohort study.Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded.Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year.Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events.The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years' initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year.Current follow-up can only detect large differences in ESKD and death outcomes.Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

  View details for PubMedID 30420158

  View details for PubMedCentralID PMC6348011

• Longitudinal study on the use of dried blood spots for home monitoring in children after kidney transplantation PEDIATRIC TRANSPLANTATION Al-Uzri, A., Freeman, K. A., Wade, J., Clark, K., Bleyle, L. A., Munar, M., Koop, D. R. 2017; 21 (6)

  Abstract

  The use of DBSs for home monitoring has been limited due to unsatisfactory blood sampling and analytical difficulties. The aim of this longitudinal feasibility trial was to assess the utility of DBS to monitor TAC and Cr at home in transplant recipients. A total of 30 participants (2-21 years, mean±SD, 13.6±5.4 year) were enrolled over 12 months. Eighteen were males. Monthly DBS samples were obtained at home and mailed to the central laboratory for analysis of TAC and Cr. Nineteen patients completed the study, and 216 cards were received in the laboratory from a total of 279 cards expected, with 416/519 (80%) blood spots being suitable for analysis. We found a high correlation between blood TAC and Cr levels by DBS and the clinical laboratory, R2 =.81 and .95, respectively. Fifteen parents and 15 youth completed measures of satisfaction with and preference for DBS testing. All but one parent/caregiver and youth reported satisfaction and preference for this method of testing over laboratory blood draws. We conclude that home DBS monitoring is a feasible method to monitor TAC and Cr in pediatric transplant recipients.

  View details for DOI 10.1111/petr.12983

  View details for Web of Science ID 000407930300004

  View details for PubMedID 28635157