Association between societal costs and treatment response in children and adolescents with ADHD and their parents. A cross-sectional study in the Netherlands.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with considerable burden of illness at a patient, family and societal level. Although pharmacological treatment is recommended by authoritative guidelines, evidence on its influence on the broader burden of illness is limited. As treatment induces costs, proper healthcare decision making requires evidence on the associated societal costs or benefits and particularly the difference that response to treatment can make. Data on ADHD related resource use of patients 8-18 years and parents were collected by means of a cross-sectional, online survey amongst members of the Dutch parent association. Children were stratified to responders and non-responders to treatment according to pre-defined expert definitions. Analyses were performed on 618 questionnaires (428 responders; 190 non-responders to treatment). Children were 11.8 years on average and mainly boys (82 %). Total monthly costs for children were €578 and €839 for responders and non-responders, respectively (p = 0.021), with a breakdown to direct medical costs (€322 vs. €512; p = 0.068), direct non-medical costs (€222 vs. €296; p = 0.090), and indirect non-medical costs (€34 vs. €57; p < 0.001). For parents, total costs were €246 vs. €399 for the responding and non-responding children, respectively (p = 0.006), with a breakdown to direct medical costs (€130 vs. €211; p = 0.010) and indirect non-medical costs (€116 vs. €181; p = 0.092). Total monthly costs of children and their parents together were €824 and €1228 for responders and non-responders to treatment, respectively (p = 0.002). These results stress the importance of a focus on response to treatment, not only beneficial for patients and their family, but also resulting in considerable societal benefits.

Probabilistic Markov Model Estimating Cost Effectiveness of Methylphenidate Osmotic-Release Oral System Versus Immediate-Release Methylphenidate in Children and Adolescents: Which Information is Needed?

BACKGROUND: Incidence of attention deficit hyperactivity disorder (ADHD) in children and adolescents has been increasing. The disorder results in high societal costs. Policymakers increasingly use health economic evaluations to inform decisions on competing treatments of ADHD. Yet, health economic evaluations of first-choice medication of ADHD in children and adolescents are scarce and generally do not include broader societal effects. OBJECTIVES: This study presents a probabilistic model and analysis of methylphenidate osmotic-release oral system (OROS) versus methylphenidate immediate-release (IR). We investigate and include relevant societal aspects in the analysis so as to provide cost-effectiveness estimates based on a broad societal perspective. METHODS: We enhanced an existing Markov model and determined the cost effectiveness of OROS versus IR for children and adolescents responding suboptimally to treatment with IR. Enhancements included screening of a broad literature base, updated utility values, inclusion of costs and effects on caregivers and a change of the model type from deterministic to probabilistic. RESULTS: The base case scenario resulted in lower incremental costs (€-5815) of OROS compared with IR and higher incremental quality-adjusted life-year (QALY) gains (0.22). Scenario analyses were performed to determine sensitivity to changes in transition rates, utility of caregivers, medical costs of caregivers and daily medication dose. CONCLUSIONS: The results indicate that, for children responding suboptimally to treatment with IR, the beneficial effect of OROS on compliance may be worth the additional costs of medication. The presented model adds to the health economic information available for policymakers and to considerations on a broader perspective in cost-effectiveness analyses.

Association between quality of life and treatment response in children with attention Deficit Hyperactivity Disorder and their parents.

BACKGROUND: It has been shown that Attention Deficit Hyperactivity Disorder (ADHD) lowers the Quality of Life (QoL) of patients and their families. Medication as part of the treatment has a favourable effect on symptoms as well as functioning. Evidence on the impact of pharmacological treatment on symptoms of ADHD and the QoL of the patient and their family is still limited. There is a need for further research on QoL in ADHD as well as the relationship between ADHD and the impact on families rather than solely on patients. AIMS OF THE STUDY: Measure QoL of children with ADHD and their parents and explore the association of QoL with treatment response. METHODS: A cross-sectional survey was performed using an online questionnaire to collect QoL data of children with ADHD (based on proxy reporting of parents) and their parents in a sample of members of an ADHD parent association. QoL was measured by EQ-5D and KIDSCREEN-10. Treatment response was based on descriptions by experts, based on compliance and functioning. RESULTS: Analyses were based on 618 questionnaires (treatment responder n=428, treatment non-responder n=190). Mean age of the children was 11.8 years (82.4% male). QoL according to EQ-5D utility was 0.83 and 0.74 for responders and non-responders, respectively (p<0.001). For KIDSCREEN-10 the index was 42.24 and 40.33 for responders and non-responders, respectively (p<0.001). EQ-5D utility scores of the parents were 0.83 on average; no association with their child's treatment response could be established. A significant positive correlation between EQ-5D utility of the children and EQ-5D utility of the parents (R2=0.207, p<0.001) was found. The association between treatment response and children's QoL was significantly influenced by age category, having a sibling with ADHD, and presence of comorbidity. DISCUSSION: Strengths of this study are its sample size and the inclusion of QoL of parents, which has not been reported simultaneously before. The facts that data were derived from members of the ADHD parent association, the data for children were based on parents' report, and lack of possibility for confirmation of the clinical diagnosis are the main study limitations. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: QoL of children with ADHD was shown to be significantly positively associated with response to treatment and negatively affected by comorbidity. In determining the treatment effects in ADHD, QoL and family overall well-being should be a standard consideration as well as an integrated part of health policy discussions on ADHD. IMPLICATIONS FOR HEALTH POLICIES: Policymakers in the field of ADHD should focus on QoL of the patient, but also on the broader effects of effective treatment on the well-being of the parents. IMPLICATIONS FOR FURTHER RESEARCH: Suggestions for further research include the repetition of this study including a control group and obtaining children's self-report on QoL and clinicians report on diagnosis.

Cost utility of telaprevir-PR (peginterferon-ribavirin) versus boceprevir-PR and versus PR alone in chronic hepatitis C in The Netherlands.

BACKGROUND: The hepatitis C virus may lead to cirrhosis, liver cancer, liver transplant, and increased mortality. With standard treatment peginterferon-alpha and ribavirin (PR), sustained viral response (SVR) was less than 50 %. SVR rates improve greatly when PR is combined with telaprevir or boceprevir. OBJECTIVES: The aim of this study was to assess the cost utility of telaprevir-peginterferon-ribavirin (TPR) versus PR and boceprevir-peginterferon-ribavirin (BPR) in treatment-naïve (TN) and treatment-experienced (TE) adults with chronic hepatitis C in the Netherlands. METHODS: A Markov model with a lifelong time horizon and annual cycles was developed. Clinical data stemmed from phase III trials (TPR vs PR, BPR vs PR). A mixed treatment comparison (MTC) was developed to compare TPR and BPR indirectly. Unit costs and utilities based on EQ-5D were established in a Dutch cross-sectional study. Cost per quality-adjusted life-years (QALYs) was calculated according to the societal perspective. RESULTS: Treating TN patients with TPR generates 1.12 additional QALYs with €333 additional cost compared with PR, resulting in an incremental cost-utility ratio of €299/QALY. In TE patients, TPR dominates PR with cost savings (-€7,819) and 1.63 additional QALYs. TPR dominates BPR yielding additional QALYs (0.26 in TN; 0.71 in TE) and cost savings (-€7,296, -€18,144, respectively). CONCLUSIONS: TPR seems a cost-effective alternative to PR in TN patients and dominant in TE patients. TPR was a dominant, more effective and less costly alternative to BPR in both patient types. The cost effectiveness of both TPR and BPR is well below generally accepted willingness-to-pay thresholds and may be considered cost effective.

Validity and responsiveness of the EQ-5D and the KIDSCREEN-10 in children with ADHD.

BACKGROUND: The aim of our study is to compare the validity of a generic preference-based Quality of Life (QoL) instrument for adults to that of a generic child-specific QoL instrument in children and adolescents with attention deficit hyperactivity disorder (ADHD). METHODS: EQ-5D and KIDSCREEN-10 data were collected using a questionnaire survey performed among parents with a child or adolescent diagnosed with ADHD. The measurements were compared to assess (dis)similarities of the instruments' constructs and responsiveness to different health states. Principal component analysis (PCA) with varimax rotation was used to identify factors underlying the constructs of both instruments. Instruments' index scores of respondents with different treatment and comorbidity profiles were compared using Student's t tests. Cohen's effect sizes were calculated for an indirect comparison of the instruments' responsiveness and discriminating ability. Separate analyses were performed in children aged 8-12 and 13-18 years. RESULTS: A strong relation was found between the EQ-5D and KIDSCREEN-10 index scores. However correlations between EQ-5D and KIDSCREEN-10 items were moderate or low. The PCA identified five separate factors of quality of life. A physical and a mental factor included a combination of three EQ-5D dimensions and six KIDSCREEN-10 items; the remaining EQ-5D and KIDSCREEN-10 items constituted complementary factors without any overlap between the separate instruments. Scores of both instruments differed significantly according to respondents' response to treatment and comorbidity profile. Cohen's effect sizes indicated comparable results of the instruments' responsiveness and discriminative ability. CONCLUSIONS: The results highlight that the instruments measure different constructs of QoL in children with ADHD. Despite this, the analyses showed comparable responsiveness and discriminative ability of the instruments. These results suggest that for economic evaluations, the EQ-5D is an appropriate and valid instrument for measuring QoL in children.

Predictors and impact of non-adherence in adults with attention-deficit/hyperactivity disorder receiving OROS methylphenidate: results from a randomized, placebo-controlled trial.

BACKGROUND: Medication non-adherence has an important impact on treatment efficacy and healthcare burden across a range of conditions and therapeutic areas. The aim of this analysis was to determine predictors of non-adherence and impact of non-adherence on treatment response in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Post-hoc analysis of a 13-week randomized, double-blind placebo-controlled study of OROS methylphenidate (MPH) 54 and 72 mg/day. Primary efficacy variable was the Conners' Adult ADHD Rating Scale - Screening Version (CAARS:O-SV). Daily adherence was calculated as average daily adherence (100 × capsules taken/2), with overall adherence calculated as the average daily adherence. Predictors of adherence were assessed using mixed-effects logistic regression. Descriptive statistics were generated for change in CAARS:O-SV score for adherent (> 95% adherence) and non-adherent subjects. Predictors of change were analyzed using a mixed model. RESULTS: Subjects were allocated to OROS MPH (54 mg, n = 87; 72 mg, n = 92) or placebo (n = 97). Mean adherence was 92.6% and 93.3% (OROS MPH 54 and 72 mg/day, respectively), versus 97.5% (placebo). Adherence was higher and less variable in completers. Factors significantly associated with non-adherence included female sex, shorter time since ADHD diagnosis, higher education level (completion of university) and score on the Drug Use Screening Inventory psychiatric disorders subscale. Improvements from baseline in CAARS:O-SV score were numerically greater in subjects defined as adherent than in those who were non-adherent. Significant predictors of CAARS:O-SV change in patients who completed the study included percentage adherence up to the point of assessment (p < 0.0001), baseline score (p < 0.0001) and family history of ADHD (p = 0.0003). CONCLUSION: The results of this analysis suggest that newly diagnosed patients, those with a high score on the DUSI-R psychiatric disorder scale, women, and subjects with high educational degrees may be at increased risk of non-adherence. Clinicians and policymakers should therefore pay special attention to these individuals, as non-adherence is a significant predictor of reduced response to treatment. TRIAL REGISTRATION: EudraCT #: 2007-002111-82.