OFFICIAL COMMUNICATIONS OF THE SSC
Recommendations for measuring health-related quality of life in children on anticoagulation
Aisha K. Bruce, KIDCLOT© Program, Stollery Children’s Hospital, University of Alberta, 3-537 11405 87 Ave NW, Edmonton, AB T6G 1C9, Canada.
Tel.: 780 248 5519; fax: 888 775 9068.
Bruce AK, Bauman ME, Jones S, Massicotte MP, Monagle P. Recommendations for measuring health-related quality of life in children on anticoagulation. J Thromb Haemost 2012; 10: 2596–8.
Quality of life (QOL) is an abstract concept that has been defined by the World Health Organization (WHO) as ‘an individual’s perception of their position in life in the context of the culture and value systems … in relation to their goals, expectations, standards, and concerns’ . The concept of health-related QOL (HRQOL) has emerged, focusing on dimensions of QOL specifically related to health and therapeutic management strategies . HRQOL in patients must be measured in order to allow the development of effective therapeutic choices, the creation of research strategies, and changes in policy for improvement of healthcare adherence and outcomes. What is considered desirable or undesirable by patients impacts on their personal QOLs, although this is not necessarily associated with morbidity as measured through medical definitions and methods. Therefore, HRQOL is now considered to be the ‘gold standard’ measurement for patient-relevant outcomes . In clinical trials, HRQOL inventories can help to distinguish between drugs with apparently equal efficacy and safety, and also to provide patient-reported adverse outcomes that might not be captured otherwise.
QOL measurement in clinical trials has been endorsed by many organizations, such as the WHO, the Food and Drug Administration, the European Agency for the Evaluation of Medical Products, and the National Institute of Health [4–6].
Growing numbers of children are requiring thromboprophylaxis. At present, children on long-term anticoagulation therapy (>3 months) are prescribed vitamin K antagonists or low molecular weight heparins, and this therapy alters their QOL . Although new agents are currently under investigation for evaluation of their pharmacodynamic, pharmacokinetic, safety and efficacy profiles in children, the impact of therapy on QOL, and hence patient preferences, must also be considered. Although pediatric patient numbers are small as compared with adults, children represent several treatment years, as many start long-term anticoagulation in their early years or infancy .
Recommendations and discussion
This position paper recommends that HRQOL be evaluated in pediatric clinical trials for emerging anticoagulation agents. Pediatric patient numbers, combined with the heterogeneity of the population, limit the ability to capture significant results with traditional outcome measurements such as safety and efficacy.
Evaluation of HRQOL in clinical trials should include the following:
- 1 Both specific and generic QOL inventories must be utilized when novel anticoagulants for children are evaluated. The use of condition-specific (HRQOL) in addition to generic QOL inventories has merit in providing a comprehensive picture of the child’s and parents’ perception of their therapy. Generic QOL inventories assess global QOL, whereas condition-specific HRQOL inventories assess the influence of a particular disease or condition on QOL. Condition-specific HRQOL inventories assess aspects of a specific health condition that are left unexplored in generic measures, and must be developed in relation to the condition. They are more sensitive to change over time, and are better discriminators of differences between subgroups within a disease category . Generic pediatric QOL inventories are widely available, validated, and reliable [10–12].
- 2 The QOL inventories used must have undergone acceptable psychometric testing. The following should be considered when the inventory is designed: purpose, focus, origins of items, opportunity for self-reporting, the threat of negative wording damaging self-esteem, number of items, time needed to complete the inventory, proxy reporting, adequate psychometric properties, and culture and language of population to be tested. Adequate psychometric properties of the QOL inventory include reliability, validity, and responsiveness testing. Further testing that is recommended by the National Institutes of Health  is either item response theory testing (IRT) or the Rasch method of testing; however, although these are laudable goals, the numbers of patients required for the performance of IRT or Rasch constitute a major limiting factor for most condition-specific QOL inventories in pediatrics. In order to maintain rigor and continue developing condition-specific QOL inventories, many authors are using new methods to compensate for the small patient volumes .
- 3 In children, the parent–child dyad, the medical team–child relationship, language, social and developmental changes and the child’s life trajectory must be considered. Children’s perspectives, goals, choices and aims change as they develop. HRQOL inventories need to be developmentally appropriate, both in content and in level of comprehension, and need to be an appropriate length for the child’s developmental age [15–18].
- 4 To complement any data collected from child HRQOL inventories, parent-proxy inventories should be included [15,16]. There is consensus among authors that parent-proxy questionnaires alone do not provide adequate and reliable data about the QOL of children, and should therefore be used as an adjunct inventory to provide an additional perspective. [15,19]. Parents commonly report their child’s health and QOL differently from how the child reports it [16,20–22], so a combination of self-report and parent-proxy reporting is ideal to give an accurate representation of QOL.
- 5 Cultural and language adaptations are required, owing to the international nature of many clinical trials, to produce versions that are conceptually equivalent . This includes forward and backward translation, and revalidation with the specific patient group within each culture. The requisite adaptations face additional challenges in children and novel strategies have been investigated to maintain sound methodology with small patient numbers .
There is currently one HRQOL anticoagulation inventory that meets the majority of the criteria for development as outlined in this article. The KIDCLOT PAC QL  is designed for the measurement of HRQOL for children on vitamin K antagonists, but can be easily modified for implementation as novel anticoagulants are evaluated, with the goal for approval for use in children. Cross-cultural and language validation is underway.
The influence of long-term anticoagulation on children’s and family’s HRQOL is that they experience difficulty with the ‘tasks’ of warfarin, such as changing the dose, capillary blood collection, venous blood collection, and remembering to give the medication . Anticoagulation does affect how children/adolescents participate in social/physical activities, and they report that their interactions with friends, diet, alcohol, rough housing and sports are negatively altered. Parents report concern regarding long-term effects of anticoagulation: family stress, feeling trapped, feeling that anticoagulation is a burden in their lives, and having their children limit their activities .
The impact that a single medication has on the lives of the patients and families cannot be understated. The emotional and physical burdens described in association with long-term anticoagulation may lead to non-adherence . Non-adherence results in decreased treatment safety and efficacy, clinical complications, and avoidable healthcare costs for both families and society . Therefore, if practitioners can identify the barriers that patients and families face with long-term anticoagulation, anticipatory interventions can be instituted. Consequently, as the licensing process is commenced for novel anticoagulants for use in pediatrics, HRQOL measurement will provide critical information for its implementation. HRQOL assessment enables more informed choices to be made about anticoagulant therapy, encouraging participation of the child and family in their health management with the goal of maximizing adherence. The ease of incorporating HRQOL measurement into clinical trial protocols and producing meaningful results consolidates the significant contribution of such an assessment.
Disclosure of conflict of interests
The authors state that they have no conflict of interest.