The Journal of Pediatrics
Volume 156, Issue 3 , Pages 350-351, March 2010

Treatment Adherence in Patients with Sickle Cell Anemia

  • Dennis Drotar, PhD

      Affiliations

    • Corresponding Author InformationReprint requests: Dennis Drotar, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 7039, Cincinnati, OH 45229-3039.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

published online 08 January 2010.

Article Outline

HbF, Percent fetal hemoglobin, SCA, Sickle cell anemia

 

See related article, p 415

Advances in the treatment of sickle cell anemia (SCA), including hydroxyurea therapy, hold the promise of improving health outcomes for children and adolescents with this very challenging chronic condition.1, 2 Close adherence to the prescribed treatment is necessary to maximize the efficacy of hydroxyurea. However, this treatment is part of a multifaceted and very demanding regimen that can include multiple medications and hydration.3 Earlier evidence suggests that adherence to the range of prescribed treatments for pediatric SCA, including hydroxyurea, is less than ideal.4, 5, 6 Consequently, there is an important need to gather clinically relevant scientific data on the prevalence and potential health-related consequences of non-adherence.

To address this need, Thornburg et al collected important data on adherence to hydroxyurea therapy for 75 children with SCA in a cross-sectional study.7 The primary findings were that adherence was: (1) >75% for 4 of 5 measures that were studied; (2) variable across different measures and lowest for pharmacy refill data; and (3) related to percent fetal hemoglobin (HbF; ie, higher adherence related to greater HbF). One of the important strengths of their study design was the inclusion of multiple measures of adherence based on different informants (eg, parent report, physician provider report, and methods, including pharmacy prescription refill data).7 This is important because adherence can be assessed from many perspectives. Moreover, valid objective indicators of adherence to hydroxyurea treatment are not readily available in practice.

Another strength of the study was the analysis of the association of measures of treatment adherence with a clinical outcome, in this case HbF. These data address one of the most important priorities in the science of treatment adherence, that is to document the potential contribution of adherence to hydroxyurea treatment and pediatric health-related outcomes including symptoms, clinically relevant physiologic indices of disease control, and health care use.8 Several adherence measures related positively and in the predicted direction with HbF, increasing confidence in the findings and underscoring the need to consider their potential clinical application.

However, several methodological issues should be considered. In particular, parental reports may have overestimated children's actual adherence to hydroxyurea treatment. Other studies have shown that parent and child reports of treatment adherence overestimate rates of adherence compared with more objective methods such as electronic monitoring, bioassay, or pharmacy records.9 Thornburg et al7 found that treatment adherence as measured with parental report was 82% compared with 49% measured on the basis of pharmacy refill records.

Future studies should build on these findings to assess adherence to hydroxyurea treatment on the basis of an objective method, such as electronic monitoring of oral medication.9 Electronic monitoring has the advantage of specifying both the timing and frequency of medication use that occurs in real time and the duration of gaps in adherence to prescribed treatment. Moreover, integrating electronic monitoring data that can estimate the frequency and timing of the doses of medications with pharmacological methods that measure individual differences in biologic responsiveness to medication treatment can help to distinguish biologic- versus adherence-related influences (and interactions between these factors) on health outcomes such as HbF. Multisite studies with larger sample sizes will be needed to have sufficient power to detect such effects. Prospective research is also needed to determine the predictive power of treatment adherence to changes in health outcomes in SCA with time. Moreover, data are needed to establish the minimal or threshold level of treatment adherence to hydroxyurea necessary to achieve beneficial effects on critical health outcomes.

One of the important next steps in adherence research related to hydroxyurea treatment is to describe the feasibility, clinical usefulness, and effectiveness of adherence measurement and adherence promotion interventions in ongoing clinical care for SCA. In typical patterns of care for chronic conditions, non-adherent children and families may not be identified until these problems are sufficiently severe to impact health. For this reason, implementing valid methods to assess treatment adherence9 and patients' and parents' perceptions of barriers10 in clinical follow-up for SCA are important future directions. Although non-adherence to treatment can be difficult to change, targeted methods of comprehensive behavioral and educational interventions have demonstrated positive effects.11 The principles of effective behavioral interventions, such as family communication and problem-solving to address barriers to treatment adherence, can be integrated in ongoing clinical management of pediatric chronic conditions.12 Future research should evaluate the efficacy of strategies of adherence promotion to hydroxyurea and other treatments for SCA that are delivered in the context of comprehensive care.

Back to Article Outline

References 

  1. Hankins JS, Ware RE, Rogers ZR, Wynn LW, Lane PA, Scott JP, et al. Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. Blood. 2005;106:2269–2275
  2. Brawley OW, Cornelius LJ, Edwards LR, Gamble VN, Green BL, Inturrisi C, et al. National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. 2008;148:932–938
  3. Lemanek KL, Ranalli M. Sickle Cell Disease. In:  Roberts MC,  Steele RG editor. Handbook of pediatric psychology. 4th ed. New York & London: The Guilford Press; 2009;
  4. Barakat LP, Smith-Whitley K, Ohene-Frempong K. Treatment adherence in children with sickle cell disease: disease-related risk and psychosocial resistance factors. J Clin Psychol Med Settings. 2002;9:201–209
  5. Witherspoon D, Drotar D. Correlates of adherence to prophylactic penicillin therapy in children with sickle cell disease. Children's Health Care. 2006;35:281–296
  6. de Montalembert M, Brousse V, Elie C, Bernaudin F, Shi J, Landais P. Long-term hydroxyurea treatment in children with sickle cell disease: tolerance and clinical outcomes. Haematologica. 2006;91:125–128
  7. Thornburg CD, Calatroni A, Telen M, Kemper AR. Adherence to hydroxyurea therapy in children with sickle cell anemia. J Pediatr. 2010;156:415–419
  8. Pai ALH, Drotar D. Treatment adherence impact: the systematic assessment and quantification of the impact of treatment adherence on pediatric medical and psychological outcomes. J Pediatr Psychol. In press 2009.
  9. Bender BG, Bartlett SJ, Rand CS, Turner C, Wamboldt FS, Zhang L. Impact of interview mode on accuracy of child and parent report of adherence with asthma-controller medication. Pediatrics. 2007;120:e471–e477
  10. Modi AC, Crosby LE, Guilfoyle SM, Lemanek KL, Witherspoon D, Mitchell MJ. Barriers to treatment adherence for pediatric patients with sickle cell disease and hteir families. Child Health Care. 2009;38:107–122
  11. Kahana S, Drotar D, Frazier T. Meta-analysis of psychological interventions to promote adherence to treatment in pediatric chronic health conditions. J Pediatr Psychol. 2008;33:590–611
  12. Pai ALH, Drotar D. Medication adherence in pediatric oncology. In:  Kazak AE,  Kupst MJ,  Pao M,  Patenaude AF,  Wiener L editor. Quick reference for oncology clinicians: the psychiatric and psychological dimensions of cancer symptom management. Charlottesville, VA: IPOS Press; 2009;p. 90–96

PII: S0022-3476(09)01080-4

doi:10.1016/j.jpeds.2009.10.035

Refers to article:

  • Peanut Allergy Saves a Patient with Cold-Induced Hypotension and Urticaria , 08 January 2010

    J. Andrew Bird, Wesley Burks
    The Journal of Pediatrics April 2010 (Vol. 156, Issue 4, Page 687)

  • Adherence to Hydroxyurea Therapy in Children with Sickle Cell Anemia , 02 November 2009

    Courtney D. Thornburg, Agustin Calatroni, Marilyn Telen, Alex R. Kemper
    The Journal of Pediatrics March 2010 (Vol. 156, Issue 3, Pages 415-419)

The Journal of Pediatrics
Volume 156, Issue 3 , Pages 350-351, March 2010

Article Tools