Identification and Characterization of Clinical, Humanistic and Economic Outcomes and Clinical Endpoints in Vaso Occlusive Crisis of Sickle Cell Disease – A Systematic Review

Health outcomes often serve as a measure of treatment efficacy in clinical studies. Although self-reported, observational, & clinical techniques exist for assessing treatment efficacy in Vaso Occlusive Crisis (VOC) of Sickle Cell Disease (SCD) for both pediatric & adult populations; it is necessary to evaluate quality of evidence available in support of these techniques before they can be used with confidence.

I. To assess quality of evidence available in support of clinical, humanistic & economic outcomes & clinical endpoints of VOC of SCD.

II. To identify & characterize clinical, humanistic & economic outcomes & clinical endpoints for assessment of treatment efficacy of VOC of SCD from literature.

Potentially relevant articles were searched electronically using terms related to VOC & pain crisis in SCD, across PubMed, COCHRANE & CINAHL databases. Dissertations, guidelines, abstracts, conference proceedings & case reports were excluded for lack of sufficient information. Reference lists of prior literature reviews, as well as reference lists of studies included in this review, served to identify additional articles. Only blinded randomized studies with a control group in treating VOC of SCD were included for further analyses. Qualified studies were searched for relevant clinical, humanistic, economic outcomes & clinical endpoints, which have previously been defined elsewhere. Qualified studies were assessed utilizing AHRQ's recommended Evidence based Practice Center- Strength of Evidence (EPC-SOE) methodology. EPC-SOE grades evidence across four primary domains: risk of bias, consistency, precision & directness. Evidence was also assessed for publication bias. Consequently, an overall grade of evidence for each outcome category was assigned.

1,917 potentially relevant study abstracts were identified & reviewed. Of these, 39 studies qualified for analyses. On assessment of the quality of evidence employing EPC-SOE methodology (Table 1), Humanistic outcomes were found to have the highest overall strength of evidence, whereas, clinical outcomes & clinical endpoints were found to have moderate overall strength of evidence. Economic outcomes were graded ‘insufficient’ due to lack of published studies. Studies were observed to use more than one outcome measure (25 studies) for assessing treatment efficacy, compared to a single measure (14 studies). 23 humanistic outcomes, 7 clinical outcomes, 6 clinical endpoints & 3 economic outcomes are available to assess treatment efficacy in VOC of SCD. Majority of the studies utilize Visual Analogue Scale (VAS) (14 studies) & Facial contours-based pain scales (5 studies) as humanistic outcome measures. Time to resolution (15 studies) & length of stay (13 studies) are preferred clinical outcome measures whereas amount of analgesics required during a VOC event (14 studies) are preferred clinical endpoints.

Evidence suggests that humanistic outcomes reflect true treatment effect & further research is very unlikely to change our confidence in using these measures as possible treatment efficacy endpoints. Whereas, assessment of our evidence reflects moderate confidence in using clinical outcomes & clinical endpoints as treatment efficacy endpoints & further research may suggest otherwise. A combination of humanistic & clinical outcomes & clinical endpoints rather than a single outcome measure, is a method of choice to assess treatment efficacies. Evidence however, is inconclusive towards using Economic outcomes as a possible endpoint.

Thomas:Pfizer: Consultancy, Research Funding. Shafer:Pfizer: Employment. Sivamurthy:Pfizer: Employment. Kollmer:Pfizer: Employment, Equity Ownership. Vendetti:Pfizer: Employment.