Challenges of Cost-Effectiveness Analyses of Novel Therapeutics for Inherited Retinal Diseases

Jayasundera, Thiran; Abuzaitoun, Rebhi; Lacy, Gabrielle D.; Abalem, Maria Fernanda; Saltzman, Gregory M.; Ciulla, Thomas A; Johnson, Mark W.

doi:10.1016/j.ajo.2021.08.009

Cited by 12 publications

(11 citation statements)

References 38 publications

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“…Although with the higher cost, potentially curative gene therapy offers the possibility of lifelong benefits from a single course of treatment, which could lead to these therapies being more cost-effective than current treatments in the long term ( Ho et al, 2021 ). Therefore, the cost-effectiveness of gene therapy should be carefully considered from clinical trials to clinical practice ( Jayasundera et al, 2022 ).…”

Section: Gene Therapy Of Refractory Hypercholesterolemiamentioning

confidence: 99%

The Progression of Treatment for Refractory Hypercholesterolemia: Focus on the Prospect of Gene Therapy

2022

Front. Genet.

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Refractory hypercholesterolemia (RH), including homozygous familial hypercholesterolemia (HoFH) and compound heterozygous familial hypercholesterolemia, is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) despite existing cholesterol-lowering methods at maximal tolerable doses. Patients with RH have early onset and higher risk of atherosclerotic cardiovascular disease (ASCVD) under insufficient treatment. Therefore, it is urgent to seek new therapies to maintain the blood lipids in refractory hyperlipidemia at normal levels. Currently, new cholesterol-lowering strategies are on the market, not only at the protein level [i.e., bempedoic acid (inhibiting ATP-citrate lyase), alirocumab and evolocumab (monoclonal antibodies against PCSK9), evinacumab (monoclonal antibody against ANGPTL3)] but also at the transcript level [i.e., mipomersen (antisense oligonucleotide inhibiting ApoB), inclisiran (siRNA targeting PCSK9)], providing more options for RH patients to achieve their lipid-lowering targets. More RNA-based therapies targeting RH-related genes have been designed for the treatment. However, for a proportion of patients, especially those with LDLR deficiency, the available treatments are still insufficient. More recently, emerging genome engineering based on CRISPR/Cas9 techniques, and advanced delivery technologies such as lentiviral vectors, adenoviral vectors, adeno-associated viral vectors, lipid nanoparticles, and exosomes are being rapidly developed and implemented as novel therapies for RH. Gene therapy targeting RH-related genes has been successfully conducted in cells, mice, and non-human primates with high efficacy in lipid lowering and good tolerability. Especially the new generation of genome editing technique, base editing, performed in vivo with ideal lipid-lowering effect and limited occurrence of unwanted results. Excitingly, a phase I/II clinical study of LDLR gene replacement has been recently completed in RH patients, likely to be employed in clinical practice in the future. Furthermore, new targets for cholesterol reduction such as REV-ERB, G protein-coupled receptor, Ubiquitin specific peptidase 20 are continually being developed. This narrative review updates recent advances in treatment for RH, summarizes related clinical trials and preclinical studies, especially on the prospect of gene therapy.

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Section: Gene Therapy Of Refractory Hypercholesterolemiamentioning

confidence: 99%

The Progression of Treatment for Refractory Hypercholesterolemia: Focus on the Prospect of Gene Therapy

2022

Front. Genet.

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“…A validated PROM should be created by incorporating an in-depth qualitative analysis of patient input (i.e., interviews or focus groups) and thorough quantitative psychometric analysis to establish the measure’s validity, interpretability, reliability, and ability to detect a change in the target population. When coupled with other clinical tests, well-designed PROMs can holistically measure a therapeutic impact on a patient’s daily life [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

The State of Patient-Reported Outcome Measures for Pediatric Patients with Inherited Retinal Disease

et al. 2022

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Patient-reported outcome measures (PROMs) are questionnaires that assess health outcomes meaningful to the patient. PROMs have multiple applications, such as supporting clinicians’ decision-making for patient care, understanding the impact of disease on patient functioning, and evaluating the efficacy of therapeutics. Though PROMs were developed for various eye conditions, no PROM was tailored to pediatric patients with inherited retinal disease (IRD). Hence, a literature search was conducted using MEDLINE and Embase to identify PROMs potentially relevant to this patient population. This review evaluated selected pediatric PROMs against the US Food and Drug Administration (FDA) guidelines and found restricted use in the context of IRD. As there is a need for PROMs tailored to pediatric patients with IRD, we provide a perspective on applying the International Society for Pharmacoeconomics and Outcomes Research and FDA standards on the development of PROMs specific to IRD. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-022-00514-x.

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“…Further understanding of the underlying issues with the EQ-5D index in ophthalmic diseases can be gained by investigating predictors of individual EQ-5D health dimensions. This is of particular importance at a time when new treatments such as gene therapy are becoming available and cost-effectiveness studies are needed [38,39]. The aim of this study was to identify predictors of health dimensions measured by the EQ-5D-3L in a sample of people with impaired vision due to a spectrum of eye diseases.…”

Section: Introductionmentioning

confidence: 99%

Predictors of problems reported on the EQ-5D-3L dimensions among people with impaired vision in northern Portugal

Macedo

Hellström

Massof

et al. 2022

Health Qual Life Outcomes

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Background The EQ-5D index often fails to detect the effect of ophthalmic diseases and sight loss. Investigating predictors of individual EQ-5D health dimensions might reveal the underlying reasons. The aim of this study was to investigate predictors of health dimension ratings obtained with the EQ-5D-3L from participants with impaired vision representing a spectrum of eye diseases. Methods Observational cross-sectional study with participants recruited at four public hospitals in Portugal. Outpatients with visual acuity of 0.30 logMAR(6/12) or worse in the better-seeing eye were invited to participate. Participants completed two instruments: the EQ-5D-3L (measures participants’ perceived health-related quality-of-life) and the Massof Activity Inventory (measures visual ability–ability to perform vision-related activities). This study used logistic regression models to identify factors associated with responses to the EQ-5D-3L. Results The study included 492 participants, mean age 63.4 years (range = 18–93), 50% females. The most common diagnosis was diabetic retinopathy (37%). The mean visual acuity in the better seeing eye was 0.65 logMAR (SD = 0.48) and the mean visual ability was 0.62 logits (SD = 2.04), the correlation between the two was r = − 0.511 (p < 0.001). Mobility and self-care were the health dimensions with the fewest problems (1% reported extreme problems), anxiety and depression the dimension with the most problems (24% reported extreme problems). ROC curve analysis showed that the EQ-5D index was a poor predictor of cases of vision impairment whilst visual ability given was a good predictor of cases of vision impairment. Visual ability was an independent predictor of the response for all dimensions, higher ability was always associated with a reduced odds of reporting problems. The odds of reporting problems were increased for females in 3 out of 5 dimensions. Comorbidities, visual acuity and age-category were predictors of the odds of reporting problems for one dimension each. Conclusions The odds of reporting problems for the five health dimensions of the EQ-5D-3L were strongly influenced by the ability to perform vision-related activities (visual ability). The EQ-5D index showed poor performance at detecting vision impairment. These findings are informative and relevant for the clinic and for research evaluating the impact of eye diseases and disease treatments in ophthalmology.

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Challenges of Cost-Effectiveness Analyses of Novel Therapeutics for Inherited Retinal Diseases

Cited by 12 publications

References 38 publications

The Progression of Treatment for Refractory Hypercholesterolemia: Focus on the Prospect of Gene Therapy

The Progression of Treatment for Refractory Hypercholesterolemia: Focus on the Prospect of Gene Therapy

The State of Patient-Reported Outcome Measures for Pediatric Patients with Inherited Retinal Disease

Predictors of problems reported on the EQ-5D-3L dimensions among people with impaired vision in northern Portugal

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