title: Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.
abstract: BACKGROUND
  After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy.
  
  
  METHODS
  The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation.
  
  
  RESULTS
  A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse effects (p=0.008) in renal transplant recipients receiving tacrolimus and mycophenolic acid compared to the cyclosporine regimen. This finding demonstrated construct validity. Intra-class correlation was 0.81 (95% confidence interval: 0.65-0.90) and Kappa statistic of 0.68 ± 0.25 for all 18 adverse effects and verified substantial inter-rater reliability.
  
  
  CONCLUSIONS
  This immunosuppressive adverse effects scoring system in stable renal transplant recipients was evaluated and substantiated face, content and construct validity with inter-rater reliability. The scoring system may facilitate prospective, standardized clinical monitoring of immunosuppressive adverse drug effects in stable renal transplant recipients and improve medication adherence.
authors.affiliation: Immunosuppressive Pharmacology Research Program, Translational Pharmacology Core, NYS Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, New York 14203, USA. cjmeaney@buffalo.edu.
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Meaney
authors.forename: Ziad
authors.initials: Z
authors.lastname: Arabi
authors.forename: Rocco C
authors.initials: RC
authors.lastname: Venuto
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Consiglio
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Wilding
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Tornatore
mesh_terms: D001927:Brain Diseases / Q000139:chemically induced* / Q000145:classification / Q000175:diagnosis*; D019703:Calcineurin; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000145:classification / Q000175:diagnosis*; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D019703:Calcineurin