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Keratoconus is a burden to health systems and patients worldwide. Corneal collagen crosslinking (CXL) treatment has been shown abroad to be cost-effective for treating progressive keratoconus. However, no cost-effectiveness studies have been performed in Brazil. The aim of this study was to assess the cost-effectiveness of corneal collagen crosslinking (CXL) compared with the conventional treatment for progressive keratoconus from the Brazilian Unified Health System (SUS) payer's perspective. A lifetime microsimulation model was utilized to compare the lifetime costs and quality-adjusted life years for patients undergoing corneal collagen CXL or conventional treatment. Two groups of 5000 18-year-old patients were simulated, with one group receiving corneal CXL at the outset and the control group remaining untreated. The TreeAge Pro Healthcare 2024 software was used for modeling and analysis. Corneal collagen CXL demonstrated superior cost-effectiveness compared to the conventional treatment, with an incremental cost-effectiveness ratio of 58.26 USD/quality-adjusted life years (QALY) gained (95% CI: 58.17-58.36) and a positive incremental net monetary benefit of USD 11,613.82 (95% CI: 11,605.66-11,621.99). CXL significantly reduced the number of required corneal transplants, with a mean of 968.8 (95% CI: 959-978.58) fewer transplants per 10,000 eyes treated. The variable with the most significant impact on the incremental net monetary benefit was the duration of the CXL effect. This study concluded that corneal CXL is a highly cost-effective intervention for progressive keratoconus within the Brazilian SUS. These findings advocate for broader accessibility to this vision-saving treatment within the SUS.

Purpose: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) has been an essential tool in the 'standard of care' of malignant gliomas. Over the last two decades, its indications have been extended to other neoplasms, such as metastases and meningiomas. However, its availability and cost-benefit still pose a challenge for widespread use. The present article reports a retrospective series of 707 cases of central nervous system (CNS) tumors submitted to FGR with pharmacological equivalent 5-ALA and discusses financial implications, feasibility and safeness., Methods: From December 2015 to February 2024, a retrospective single institution series of 707 cases of 5-ALA FGR were analyzed. Age, gender, 5-ALA dosage, intraoperative fluorescence finding, diagnosis and adverse effects were recorded. Financial impact in the surgical treatment cost were also reported., Results: there was an additional cost estimated in $300 dollars for each case, increasing from 2,37 to 3,28% of the total hospitalization cost. There were 19 (2,69%) cases of asymptomatic photosensitive reaction and 2 (0,28%) cases of photosensitive reaction requiring symptomatic treatment. 1 (0,14%) patient had a cutaneous rash sustained for up to 10 days. No other complications related to the method were evident. In 3 (0,42%) cases of patients with intracranial hypertension, there was vomiting after administration., Conclusion: FGR with pharmacological equivalent 5-ALA can be considered safe and efficient and incorporates a small increase in hospital expenses. It constitutes a reliable solution in avoiding prohibitive costs worldwide, especially in countries where commercial 5-ALA is unavailable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Basal cell carcinoma is the most common cancer. Excisional surgery is associated with a high clearance rate, at the expense of significant functional and aesthetic morbidity, especially within the T-zone or for extensive lesions. We report five-year follow-up outcomes for carbon dioxide laser extirpation of cutaneous basal cell carcinoma, assisted by immediate methyl aminolevulinate photodynamic therapy and cost-benefit considerations., Materials and Methods: Retrospective cohort database analysis of adult patients with biopsy-proven primary cutaneous basal cell carcinoma, completing five years of follow-up. Direct per-lesion cost was compared with conventional wide local excision. Patients with morphoeic basal cell carcinoma were excluded., Results: Treated lesions were up to 1% total body surface area and up to 3.8mm (1.38 ± 0.695cm, mean ± standard deviation) in biopsy-proven depth. At the five-year follow-up mark, 93.6% of treated areas remained free of recurrence. Nodular basal cell carcinoma was the most common subtype (41.5%). A mean tumour depth greater than 2 ± 0.872mm was significantly associated with recurrence (Mann-Whitney, p  = 0.0487). For a service delivered through the NHS at 2015 prices, we report a 43% saving, equating to a saving of £235 per basal cell carcinoma or a national annualised saving of £70 million by 2025 for the NHS., Conclusion: Our results suggest that CO 2 -assisted photodynamic therapy is non-inferior to excision but may offer better functional and cosmetic preservation at a fraction of the direct like for like cost of operative surgery. Investigation of this method by randomised controlled methodology is warranted.

Importance: The EVEREST II trial showed that for patients with polypoidal choroidal vasculopathy (PCV), intravitreal ranibizumab in combination with verteporfin photodynamic therapy improves visual acuity relative to ranibizumab monotherapy. However, whether combination therapy is incrementally cost-effective relative to monotherapy during a lifetime is unclear., Objective: To assess the incremental cost-effectiveness of combination therapy compared with ranibizumab monotherapy in patients with PCV., Design, Setting, and Participants: This model-based, economic evaluation used 2018 unit cost data from a tertiary eye hospital in Singapore, first- and second-year outcomes and resource use data from a multicenter trial across various Asian countries (EVEREST II) to model a hypothetical cohort of patients with symptomatic PCV. Scenario analyses and deterministic and probabilistic sensitivity analyses were performed to examine uncertainty. Data were collected from October 2018 through April 2019 and analyzed from March through October 2019., Interventions: This model used data from the EVEREST II trial, in which all participants were given 0.5 mg of intravitreal ranibizumab once every 4 weeks for the first 3 months. Subsequent administration occurred as needed. For participants receiving combination therapy, standard fluence (50 J/cm3) photodynamic therapy with 6-mg/m2 verteporfin was administered once during the first 3 months and thereafter as needed., Main Outcomes and Measures: Incremental cost per quality-adjusted life-year (QALY) gained for combination therapy relative to monotherapy for patients with PCV., Results: In this model based on a cohort of 1000 patients aged 68 years, a patient with PCV incurred a total cost in Singapore dollars (SGD) of 92 327 (US $67 399) with combination therapy and SGD 92 371 (US $67 431) with monotherapy during a lifetime horizon, generating a modest cost savings of SGD 44 (US $32) per patient undergoing combination therapy. Lifetime QALYs were estimated to be 7.87 for combination therapy and 7.85 for monotherapy, for an incremental gain of 0.02 QALYs. Combination therapy remained cost-saving or cost-effective in all lifetime scenarios modeled, but during shorter time horizons and at lower monotherapy costs, it may not be cost-effective., Conclusions and Relevance: This study found combination therapy to be a dominant (more effective and less costly) strategy, being similar in costs and slightly more effective than ranibizumab monotherapy during a lifetime horizon. However, decreasing the time horizon to less than 10 years and/or reductions in the cost of monotherapy may result in combination therapy no longer being cost-effective.

Introduction: Bladder cancer is the most frequently occurring tumour of the urinary system. Ta, T1 tumours and carcinoma in situ (CIS) are grouped as non-muscle invasive bladder cancer (NMIBC), which can be effectively treated by transurethral resection of bladder tumour (TURBT). There are limitations to the visualisation of tumours with conventional TURBT using white light illumination within the bladder. Incomplete resections occur from the failure to identify satellite lesions or the full extent of the tumour leading to recurrence and potential risk of disease progression. To improve complete resection, photodynamic diagnosis (PDD) has been proposed as a method that can enhance tumour detection and guide resection. The objective of the current research is to determine whether PDD-guided TURBT is better than conventional white light surgery and whether it is cost-effective., Methods and Analysis: PHOTO is a pragmatic multicentre randomised controlled trial (open parallel group, non-masked and superiority trial) comparing the intervention of PDD-guided TURBT with standard white light resection in newly diagnosed intermediate and high risk NMIBC within the UK National Health Service setting. Clinical effectiveness is measured with time to recurrence. Cost-effectiveness is assessed within trial via the calculation of incremental cost per recurrence avoided and incremental cost per quality-adjusted life per year gained over 3 years and over long term through a modelling exercise over patients' lifetime., Ethics and Dissemination: Formal ethics review was undertaken with a favourable opinion, in line with UK regulatory procedures (REC reference number: 14/NE/1062). If reductions in time to recurrence is associated with long-term patient benefits, the cost-effectiveness evaluation will provide further evidence to inform adoption of the technology. Findings will be shared in lay media such as patient and charity forums and will be presented at key meetings and published in academic literature.Trial registration number ISRCTN84013636., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Daylight photodynamic therapy (DL-PDT) with methyl-5-aminolaevulinate (MAL) is an effective treatment for mild and moderate actinic keratosis (AK)., Objectives: To assess the clinical efficacy, tolerability and cost-effectiveness of 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) compared with MAL in DL-PDT for grade I-II AKs., Methods: This nonsponsored, prospective randomized double-blind multicentre trial included 69 patients with 767 grade I-II AKs located symmetrically on the face or scalp. A single DL-PDT was given in a randomized split-face design. The primary outcome was clearance of the AKs at 12 months as assessed by a blinded observer. The secondary outcomes were pain, treatment reactions, cosmetic outcome and the cost-effectiveness of the therapy., Results: In the per-patient (half-face) analysis, clearance was better for the BF-200 ALA sides than for those treated with MAL (P = 0·008). In total, BF-200 ALA cleared 299/375 AKs (79·7%) and MAL 288/392 (73·5%) (P = 0·041). The treatment was practically painless with both photosensitizers, the mean pain visual analogue scale being 1·51 for BF-200 ALA and 1·35 for MAL (P = 0·061). Twenty-six patients had a stronger skin reaction on the BF-200 ALA side, seven on the MAL side and 23 displayed no difference (P = 0·001). The cosmetic outcome was excellent or good in > 90% of cases with both photosensitizers (P = 1·000). The cost-effectiveness plane showed that the costs of DL-PDT were similar for both photosensitizers, but the effectiveness was slightly higher for BF-200 ALA., Conclusions: Our results indicate that BF-200 ALA is more effective than MAL in DL-PDT for grade I-II AKs. BF-200 ALA provides slightly better value for money than MAL., (© 2018 British Association of Dermatologists.)

Background: 5-Aminolevulinic acid (5-ALA) has become an important assistant in glioblastoma (GB) surgery. Unfortunately, its price affects its widespread use., Objective: The aim of this study was to compare commercial 5-ALA with the pharmacy-compounded solution., Methods: Using first an in vitro experimental approach, different concentrations of the pharmacy-compounded solution and commercial 5-ALA were tested in U87MG, LN229, U373, and T98G commercial glioblastoma cell lines. Fluorescence intensity was compared for each concentration by flow cytometry. Mean fluorescence of culture supernatant and lysate samples were analyzed. In a second phase, both preparations were used for surgical glioblastoma resection and tumor samples were analyzed by confocal microscopy. Mean fluorescence intensity was analyzed for each preparation and compared., Results: There was a high variability of fluorescence intensity between cell lines, but each cell line showed similar fluorescence for both preparations (compounded preparation and commercial 5-ALA). In the same way, both preparations had similar fluorescence intensity in glioblastoma samples., Conclusion: Both, compounded and commercial 5-ALA preparations produce equivalent fluorescent responses in human glioblastoma cells. Fluorescence intensity is cell line specific, but fluorescent properties of both preparations are undistinguishable.

Background: The cost of topical treatments for actinic keratosis (AK) has never been evaluated with respect to the actual cancerization field treated and the corresponding lesion response rate. Traditionally, evaluation in AK has been done in the context of patient response rate alone. The current study aimed to develop an economic model assessing the cost of topical treatments for the management of AK in Italy., Methods: Data from Italian patients (N.=100) with five or more mild/moderate lesions on the face and/or scalp was used. The efficacy of the topical treatments which are available for the treatment of AK in Italy was considered. The outcome of interest was lesion response rates at three months and was based on published literature. The cost of each treatment was estimated according to the approval status of the drug and the cancerization area that required treatment. The analysis was replicated for four other European countries., Results: The average costs of treatment with c-PDT, DL PDT, DHA, InMeb and IMQ were € 364.2, € 255.5, € 848.7, € 1039.1, and € 628.3, respectively. Taking into account the number of lesions cleared per patient, the cancerization area treated, and the number of visits required with each treatment, the total costs per lesion treated per patient were estimated at € 37.9, € 29, € 264.7, € 103.5, and € 115.4, respectively. The analysis produced consistent results when it was replicated for other countries., Conclusions: Daylight therapy with methyl aminolevulinate (DL PDT) is an effective treatment option for AK management with a favourable value for money profile.

Purpose: To evaluate the cost effectiveness of corneal collagen crosslinking (CXL) for progressive keratoconus from the healthcare payer's perspective., Design: A probabilistic Markov-type model using data from published clinical trials and cohort studies., Participants: Two identical cohorts, each comprising 1000 virtual patients with progressive bilateral keratoconus, were modeled; one cohort underwent CXL and the other cohort received no intervention., Methods: Both cohorts were modeled and evaluated annually over a lifetime. Quality-adjusted life years (QALYs), total cost, disease progression, and the probability of corneal transplantation, graft failure, or both were calculated based on data from published trials and cohort studies. These outcomes were compared between the 2 cohorts. In our base scenario, the stabilizing effect of CXL was assumed to be 10 years; however, longer durations also were analyzed. One-way sensitivity analyses were performed to test the robustness of the outcomes., Main Outcome Measure: Incremental cost-effectiveness ratio (ICER), defined as euros per QALY., Results: Assuming a 10-year effect of CXL, the ICER was €54 384/QALY ($59 822/QALY). When we adjusted the effect of CXL to a lifelong stabilizing effect, the ICER decreased to €10 149/QALY ($11 163/QALY). Other sensitivity and scenario analyses that had a relevant impact on ICER included the discount rate, visual acuity before CXL, and healthcare costs., Conclusions: Corneal collagen crosslinking for progressive keratoconus is cost effective at a willingness-to-pay threshold of 3 times the current gross domestic product (GDP) per capita. Moreover, a longer stabilizing effect of CXL increases cost effectiveness. If CXL had a stabilizing effect on keratoconus of 15 years or longer, then the ICER would be less than the 1 × GDP per capita threshold and thus very cost effective., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To use patient-level microsimulation models to evaluate the comparative cost-effectiveness of early corneal cross-linking (CXL) and conventional management with penetrating keratoplasty (PKP) when indicated in managing keratoconus in Canada., Design: Cost-utility analysis using individual-based, state-transition microsimulation models., Participants: Simulated cohorts of 100 000 individuals with keratoconus who entered each treatment arm at 25 years of age. Fellow eyes were modeled separately. Simulated individuals lived up to a maximum of 110 years., Methods: We developed 2 state-transition microsimulation models to reflect the natural history of keratoconus progression and the impact of conventional management with PKP versus CXL. We collected data from the published literature to inform model parameters. We used realistic parameters that maximized the potential costs and complications of CXL, while minimizing those associated with PKP. In each treatment arm, we allowed simulated individuals to move through health states in monthly cycles from diagnosis until death., Main Outcome Measures: For each treatment strategy, we calculated the total cost and number of quality-adjusted life years (QALYs) gained. Costs were measured in Canadian dollars. Costs and QALYs were discounted at 5%, converting future costs and QALYs into present values. We used an incremental cost-effectiveness ratio (ICER = difference in lifetime costs/difference in lifetime health outcomes) to compare the cost-effectiveness of CXL versus conventional management with PKP., Results: Lifetime costs and QALYs for CXL were estimated to be Can$5530 (Can$4512, discounted) and 50.12 QALYs (16.42 QALYs, discounted). Lifetime costs and QALYs for conventional management with PKP were Can$2675 (Can$1508, discounted) and 48.93 QALYs (16.09 QALYs, discounted). The discounted ICER comparing CXL to conventional management was Can$9090/QALY gained. Sensitivity analyses revealed that in general, parameter variations did not influence the cost-effectiveness of CXL., Conclusions: CXL is cost-effective compared with conventional management with PKP in the treatment of keratoconus. Our ICER of Can$9090/QALY falls well below the range of Can$20 000 to Can$100 000/QALY and below US$50 000/QALY, thresholds generally used to evaluate the cost-effectiveness of health interventions in Canada and the United States. This study provides strong economic evidence for the cost-effectiveness of early CXL in keratoconus., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Some basal cell carcinomas (BCCs) are indistinguishable from nevi based on clinical manifestations. Therefore, it is often difficult for the excision margins of the initial surgical treatment to achieve radical removal of the malignancy. This study was a comparative analysis of the clinical results of aminolevulinic acid (ALA)-photodynamic therapy (PDT) or secondary surgery after the primary excision. In total, 20 patients with preoperative clinical diagnoses of nevi underwent in situ resection. The postoperative pathological diagnoses confirmed all cases were BCC. Ten patients received PDT twice after the primary excision, and 10 cases received extended resection after the primary excision. Patients were followed up for 8 months at least, and the 2 groups did not show statistically significant differences in the recurrence rate, while the PDT group had better results in terms of economic burden, healing period, and cosmetic satisfaction than the group with secondary surgery. Our study demonstrates that ALA-PDT can sever as a considerable remedial treatment for the BCC patients who have not accepted radical resection due to primary clinical misdiagnosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: This analysis estimated the cost-effectiveness of intravitreal aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD) compared with other treatments in Japan., Methods: This was a cost-utility analysis based on published data. A state-transition cohort model was constructed with six health states based on best-corrected visual acuity in the better-seeing eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model compared IAI 2 mg every 8 weeks (2q8) for 2 years after three initial monthly injections, ranibizumab as needed, ranibizumab 0.5 mg every 4 weeks (0.5q4), pegaptanib sodium 0.3 mg every 6 weeks, verteporfin photodynamic therapy (PDT), and best supportive care, assumed to include medical management and monitoring, but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality-adjusted life years (QALYs) gained were estimated for each treatment and discounted at 2.0%. Input data were obtained from clinical studies, the Japanese drug tariff and social insurance reimbursement schedule, and expert opinion. The analysis was conducted from the societal perspective, including medical costs as well as costs of blindness., Results: IAI 2q8 was dominant (i.e. more effective in terms of QALYs and less costly) to all other comparators (ranibizumab as needed, ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by the incremental cost-utility ratio (i.e. cost per QALY gained)., Limitations: The strengths of the analysis include the wide range of comparators evaluated and the use of Japanese-specific utility data. The limitations include the use of one eye, inclusion of published data up to 2 years only, and assumptions on disease course over 5 years., Conclusions: IAI 2q8 was more effective in terms of QALYs and less costly compared with other treatments for wAMD in Japan.

Tissue penetration depth is a major challenge in practical photodynamic therapy (PDT). A biocompatible and highly effective near infrared (NIR)-light-absorbing carbazole-substituted BODIPY (Car-BDP) molecule is reported as a class of imaging-guidable deep-tissue activatable photosensitizers for PDT. Car-BDP possesses an intense, broad NIR absorption band (600-800 nm) with a remarkably high singlet oxygen quantum yield (Φ Δ = 67%). After being encapsulated with biodegradable PLA-PEG-FA polymers, Car-BDP can form uniform and small organic nanoparticles that are water-soluble and tumor-targetable. Rather than using laser light, such nanoparticles offer an unprecedented deep-tissue, tumor targeting photodynamic therapeutic effect by using an exceptionally low-power-density and cost-effective lamp light (12 mW cm -2 ). In addition, these nanoparticles can be simultaneously traced in vivo due to their excellent NIR fluorescence. This study signals a major step forward in photodynamic therapy by developing a new class of NIR-absorbing biocompatible organic nanoparticles for effective targeting and treatment of deep-tissue tumors. This work also provides a potential new platform for precise tumor-targeting theranostics and novel opportunities for future affordable clinical cancer treatment.

Objectives: To explore the cost impact on Swedish healthcare of incorporating one instillation of hexaminolevulinate hydrochloride (HAL) blue-light cystoscopy into transurethral resection of bladder tumour (TURBT) in patients with suspected new or recurrent non-muscle-invasive bladder cancer (NMIBC)., Materials and Methods: A decision tree model was built based on European Association of Urology guidelines for the treatment and management of NMIBC. Input data were compiled from two recent studies comparing recurrence rates of bladder cancer in patients undergoing TURBT with either the current standard of care (SOC) of white-light cystoscopy, or with the SOC and HAL blue-light cystoscopy. Using these published data with clinical cost data for surgical and outpatient procedures and pharmaceutical costs, the model reported on the clinical and economic differences associated with the two treatment options., Results: This model demonstrates the significant clinical benefits likely to be observed through the incorporation of HAL blue-light cystoscopy for TURBT in terms of reductions in recurrences of bladder cancer. Analysis of economic outputs of the model found that the use of one instillation of HAL for TURBT in all Swedish patients with NMIBC is likely to be cost-neutral or cost-saving over 5 years relative to the current SOC of white-light cystoscopy., Conclusions: The results of this analysis provide additional health economic rationale for the incorporation of a single instillation of HAL blue-light cystoscopy for TURBT in the treatment of patients with NMIBC in Sweden., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Actinic keratoses (AK) occur frequently; however, real-life clinical data on personalized treatment choice and costs are scarce. This multicentre one-year observational study investigated patient-characteristics, cost and effectiveness of methylaminolaevulinate photodynamic therapy (MAL-PDT), imiquimod (IMI) and 5-fluorour-acil (5-FU) in patients with AKs on the face/scalp. A total of 104 patients preferred MAL-PDT, 106 preferred IMI and 110 preferred 5-FU. At baseline, significant differences between treatment groups were found; most patients were severely affected (mean 32.5 AK in PDT-group, 20.2 in IMI-group, 22.8 in 5-FU-group). A mean reduction in lesions of 81% after MAL-PDT, 82% after IMI and 88% after 5-FU was found after one year. Annual costs were €1,950 for MAL-PDT, €877 for IMI and €738 for 5-FU. These results show that, compared with clinical trials, in the real-life clinical setting AK patients are usually more severely affected and treatment costs are much higher. Furthermore, patient characteristics are important factors in treatment choice.

Background: A recent noninferiority randomized trial showed that in terms of clinical effectiveness imiquimod was superior and topical fluorouracil noninferior to methylaminolaevulinate photodynamic therapy (MAL-PDT) for treatment of superficial basal-cell carcinoma (sBCC). Although it was expected that MAL-PDT would be more costly than either cream, a full cost-effectiveness analysis is necessary to determine the balance between effectiveness and costs., Objective: To determine whether imiquimod or topical fluorouracil are cost-effective treatments for sBCC compared with MAL-PDT., Methods: An economic evaluation was performed from a healthcare perspective. Data on resource use and costs were collected alongside the randomized clinical trial. The incremental cost-effectiveness ratio was expressed as the incremental costs per additional patient free of tumour recurrence., Results: At 12 months follow-up, the total mean costs for MAL-PDT were €680, for imiquimod cream €526 and for topical fluorouracil cream €388. Both imiquimod and topical fluorouracil were cost-effective treatments compared with MAL-PDT. Comparing costs and effectiveness of both creams led to a incremental investment of €4451 to achieve an additional patient free of tumour recurrence. The acceptability curve showed that, for a threshold value of €4451, the probability of imiquimod being more cost-effective than topical fluorouracil was 50%., Conclusion: Based on the 12 months follow-up results, imiquimod and topical fluorouracil cream are more cost-effective than MAL-PDT for treatment of sBCC. Hence, substituting MAL-PDT with either imiquimod or topical fluorouracil results in cost savings; these savings will be larger for topical fluorouracil. Long-term follow-up effectiveness data are necessary to confirm the cost-effectiveness of imiquimod vs. topical 5-fluorouracil cream., (© 2014 British Association of Dermatologists.)

Purpose: The aim of this study was to evaluate the cost effectiveness of ranibizumab compared with verteporfin photodynamic therapy (vPDT) or no treatment (observation) in patients with visual impairment due to myopic choroidal neovascularization (CNV)., Methods: A Markov model with health states defined by best-corrected visual acuity and a 3-month cycle length was developed. It had a healthcare provider (UK National Health Service and personal social services) perspective, a lifetime time horizon, and was based on 2011 prices; future costs and health outcomes were discounted at 3.5 % per annum. Baseline characteristics were based on the phase III RADIANCE (Ranibizumab and vPDT Evaluation in Myopic CNV) study, and year 1 health-state transitions were based on this and the VIP (Verteporfin in Photodynamic Therapy) study. Extensive sensitivity analyses tested the robustness of the model., Results: The lifetime cost of treating myopic CNV with ranibizumab was £12,866, whereas vPDT and observation were associated with total costs of £14,421 and £8,163, respectively. Ranibizumab treatment produced higher cumulative quality-adjusted life-years (QALYs; 12.99) than vPDT (12.60) or observation (12.45). Ranibizumab treatment was therefore dominant, with greater health gains and lower overall costs than vPDT. Ranibizumab was cost effective compared with observation, with an incremental cost-effectiveness ratio of £8,778/QALY. In the probabilistic sensitivity analysis, ranibizumab had a 100 % and 88 % probability of being cost effective compared with vPDT and observation, respectively, at a willingness-to-pay threshold of £20,000/QALY., Conclusion: This study indicates that ranibizumab therapy is dominant over vPDT for the treatment of visual impairment due to CNV secondary to pathologic myopia in the UK healthcare setting and cost effective compared with observation.

Background: A gel containing diclofenac and hyaluronic acid (DHA) and photodynamic therapy with methyl aminolaevulinate (MAL-PDT) are widely used treatments for actinic keratoses (AKs)., Objectives: The aim of this single-centre, open-label, prospective, nonsponsored, randomized controlled clinical trial was to compare the treatment results and cost-effectiveness of MAL-PDT and DHA., Methods: Patients with multiple AKs of the face and scalp were randomized to receive MAL-PDT or DHA. After 90 days, the overall complete remission (CR) rate of patients and the CR rate of lesions according to thickness score were assessed, and patients and an investigator scored the cosmetic outcome. In addition, patients scored their overall satisfaction with the treatment. Patients with CR of all lesions were followed up for 12 months., Results: Two hundred patients with a total of 1674 AKs were enrolled. The lesion CR rates at 3 months were 85·9% with MAL-PDT and 51·8% with DHA (P < 0·0001). AKs of all thicknesses were significantly more responsive to MAL-PDT. The patient CR rates at 3 months were 68% with MAL-PDT and 27% with DHA. At the 12-month examination, the number of patients with CR reduced to 37 with MAL-PDT and seven with DHA. Rating of cosmetic outcome was very good or excellent in the vast majority of patients with both treatments. The analysis of cost-effectiveness showed that the costs per patient with CR at 3 months and at 12 months are €566·7 and €1026·2, respectively, with MAL-PDT and €595·2 and €2295·6, respectively, with DHA., Conclusions: Efficacy, cosmetic outcome and patients' overall satisfaction with MAL-PDT are superior in comparison with DHA. MAL-PDT is more expensive but it is more cost-effective., (© 2014 British Association of Dermatologists.)

Aim: To compare effectiveness, safety, and cost of photodynamic therapy (PDT) and radiofrequency ablation (RFA) in treatment of Barrett's dysplasia (BD)., Methods: Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared. Thirty-three patients with high-grade dysplasia (HGD) had treatment with porfimer sodium photosensitzer and 630 nm laser (130 J/cm), with maximum of 3 treatment sessions. Fifty-three patients with BD (47 with low-grade dysplasia -LGD, 6 with HGD) had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions. Both groups received proton pump inhibitors twice daily. Endoscopic biopsies were acquired at 2 and 12 mo after enrollment, with 4-quadrant biopsies every 1 cm of the original BE extent. A complete histological resolution response of BD (CR-D) was defined as all biopsies at the last endoscopy session negative for BD. Fisher's exact test was used to assess differences between the two study groups for primary outcomes. For all outcomes, a two-sided P value of less than 0.05 was considered to indicate statistical significance., Results: Thirty (91%) PDT patients and 39 (74%) RFA were men (P = 0.05). The mean age was 70.7 ± 12.2 and 65.4 ± 12.7 (P = 0.10) year and mean length of BE was 5.4 ± 3.2 cm and 5.7 ± 3.2 cm (P = 0.53) for PDT and RFA patients, respectively. The CR-D was (18/33) 54.5% with PDT vs (47/53) 88.7% with RFA (P = 0.001). One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA. PDT was five times more costly than RFA at our institution. The two groups were not randomized and had different BD grading are the limitations of the study., Conclusion: In our experience, RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.

Context: Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC)., Objective: To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment., Evidence Acquisition: We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis., Evidence Synthesis: Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL., Conclusions: Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Our previous study has shown a prolonged retention and accumulation of Zn-pheophorbide a, a water-soluble derivative of chlorophyll a, in tumor tissue (Szczygiel et al. [19]). This prompted us to further evaluate the phototherapeutic potential of this photosensitizer of excellent physicochemical properties., Methods: Cellular uptake of Zn-pheophorbide, its localization in cells, cytotoxicity, phototoxicity and cell death mechanisms were studied in human adenocarcinoma cell lines: A549, MCF-7 and LoVo. The PDT efficacy was tested against A549 tumors growing in nude mice., Results: Zn-pheophorbide a even at very low concentrations (∼1×10(-6)M) and at low light doses (5J/cm(2)) causes a strong photodynamic effect, leading to 100% cell mortality. Confocal microscopy showed that in contrast to most derivatives of chlorophyll, Zn-pheophorbide a does not localize to mitochondria. The photodynamic effects and the cell death mechanisms of Zn-pheophorbide a, its Mg analog (chlorophyllide a) and Photofrin were compared on the A549 cells. Zn-pheophorbide a showed the strongest photodynamic effect, at low dose killing all A549 cells via apoptosis and necrosis. The very high anti-cancer potential of Zn-pheophorbide was confirmed in a photodynamic treatment of the A549 tumors. They either regressed or were markedly inhibited for up to 4 months after the treatment, resulting, on average, in a 5-fold decrease in tumor volume., Conclusion: These results show that Zn-pheophorbide a is a very promising low-cost, synthetically easily accessible, second generation photosensitizer against human cancer., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Psoralen + ultraviolet A (PUVA) therapy is an established modality for psoriasis. As India is a tropical country that has good availability of natural sunlight psoralen + sunlight (PUVAsol) may be a more convenient option. To compare the efficacy and cost-effectiveness of PUVA versus PUVAsol in chronic plaque psoriasis. Cases of chronic plaque psoriasis with body surface area ≥10% or Psoriasis Area and Severity Index (PASI) ≥10, excluding erythrodermic or pustular psoriasis, were randomized to receive either PUVA or PUVAsol, with endpoint being the achievement of PASI 90 or completion of 12 weeks treatment, whichever is earlier. Cost analysis was also undertaken. Thirty-six cases (16 in PUVA and 20 in PUVAsol group) completed treatment. In the PUVA group, 15 cases (93.75%) responded to therapy while in the PUVAsol group, 15 (75%) responded (P = 0.29). Mean baseline PASI in the PUVA and PUVAsol groups was 16 and 14.4, respectively, and at endpoint was 1.62 and 3.77. There was a significantly greater reduction in PASI in the PUVA group at 2 and 4 weeks but at 8 and 12 weeks and endpoint, it was comparable. Treatment failure occurred in 6.25% and 25% of cases respectively (P = 0.29). Side effects were higher with PUVA. Total cost of therapy was significantly higher in the PUVA group (P = 0.002). Cost-effectiveness ratio was US$0.72 with PUVA and US$0.37 with PUVAsol. Both PUVA and PUVAsol were equally efficacious, with PUVAsol being twice as cost effective. Hence, PUVAsol may be recommended as treatment for psoriasis in a developing economy such as India., (© 2013 The International Society of Dermatology.)

Purpose: Evaluation of the cost and effectiveness of therapy for patients with the wet form of age-related macular degeneration (AMD) in routine clinical practice., Methods: A retrospective multicentre evaluation of changes in the best-corrected visual acuity in applied kinds of therapy and a comparison with the cost of individual therapeutic procedures., Results: An overall total of 788 eyes of 763 patients with an average age of 73.2 ± 8.6 years was evaluated for a 1-year minimum period. In the ranibizumab and pegaptanib therapy groups, a reduction of 1.3 letters (p = 0.303) and 1.4 letters (p = 0.197) was found, respectively. In the group of photodynamic therapy (PDT) with verteporfin, a reduction of 5.2 letters was achieved (p < 0.001). Under the conditions of routine practice in the Czech Republic, the annual cost is highest (EUR 5,467.63/patient) in patients with pegaptanib therapy. The annual cost in patients with ranibizumab therapy is lower by EUR 1,220.16. The cost is nearly half (EUR 2,783.65) in the group treated with PDT with verteporfin., Conclusion: An initiation of AMD therapy by ranibizumab is cost-effective as compared to pegaptanib. Both ranibizumab and pegaptanib are significantly more efficient as compared to PDT with verteporfin. Therapy with ranibizumab and pegaptanib, as compared to PDT with verteporfin, prevents the loss of 1 line of vision on the ETDRS chart for EUR 1,225.98 and 2,286.18, respectively., (Copyright © 2013 S. Karger AG, Basel.)

Objectives: The verteporfin photodynamic therapy (VPDT) cohort study aimed to answer five questions: (a) is VPDT in the NHS provided as in randomised trials?; (b) is 'outcome' the same in the nhs as in randomised trials?; (c) is 'outcome' the same for patients ineligible for randomised trials?; (d) is VPDT safe when provided in the NHS?; and (e) how effective and cost-effective is VPDT?, Design: Treatment register., Setting: All hospitals providing VPDT in the NHS., Participants: All patients attending VPDT clinics., Interventions: Infusion of verteporfin followed by infrared laser exposure is called VPDT, and is used to treat neovascular age-related macular degeneration (nAMD). The VPDT cohort study advised clinicians to follow patients every 3 months during treatment or active observation, retreating based on criteria used in the previous commercial 'TAP' (Treatment of Age-related macular degeneration with Photodynamic therapy) trials of VPDT., Main Outcome Measures: The primary outcome was logarithm of the minimum angle of resolution monocular best-corrected distance visual acuity (BCVA). Secondary outcomes were adverse reactions and events; morphological changes in treated nAMD (wet) lesions; and for a subset of patients, 6-monthly contrast sensitivity, generic and visual health-related quality of life (HRQoL) and resource use. Treated eyes were classified as eligible for the TAP trials (EFT), ineligible (IFT) or unclassifiable (UNC)., Results: Forty-seven hospitals submitted data for 8323 treated eyes in 7748 patients; 4919 eyes in 4566 patients were treated more than 1 year before the last data submission or had completed treatment. Of 4043 eyes with nAMD in 4043 patients, 1227 were classified as EFT, 1187 as IFT and 1629 as UNC. HRQoL and resource use data were available for about 2000 patients. The mean number of treatments in years 1 and 2 was 2.3 and 0.4 respectively. About 50% of eyes completed treatment within 1 year. BCVA deterioration in year 1 did not differ between eligibility groups. EFT eyes lost 11.6 letters (95% confidence interval 10.1 to 13.0 letters) compared with 9.9 letters in VPDT-treated eyes in the TAP trials. EFT eyes had poorer BCVA at baseline than IFT and UNC eyes. Adverse reactions and events were reported for 1.4% of first visits - less frequently than those reported in the TAP trials. Associations between BCVA in the best-seeing eye with HRQoL and community health and social care resource use showed that the 11-letter difference in BCVA between VPDT and sham treatment in the TAP trials corresponded to differences in utility of 0.012 and health and social service costs of £60 and £92 in years 1 and 2, respectively. VPDT provided an incremental cost per quality-adjusted life-year (QALY) of £170,000 over 2 years., Conclusions: VPDT was administered less frequently than in the TAP trials, with less than half of those treated followed up for > 1 year in routine clinical practice. Deterioration in BCVA over time in EFT eyes was similar to that in the TAP trials. The similar falls in BCVA after VPDT across the pre-defined TAP eligibility groups do not mean that the treatment is equally effective in these groups because deterioration in BCVA can be influenced by the parameters that determined group membership. Safety was no worse than in the TAP trials. The estimated cost per QALY was similar to the highest previous estimate. Although VPDT is no longer in use as monotherapy for neovascular AMD, its role as adjunctive treatment has not been fully explored. VPDT also has potential as monotherapy in the management of vascular malformations of the retina and choroid and with trials underway in neovascularisation due to myopia and polypoidal choroidopathy., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background and Objectives: Standard treatments of high-grade Cervical intraepithelial neoplasia (CIN) are conisation procedures. Theses methods have proven effectiveness but are associated with an increased risk of subsequent pregnancy complications. Recently, photodynamic therapy (PDT) of CIN using hexylaminolevulinate (HAL) may represent an alternative treatment without the risk of cervical insufficiency or scaring. This study aims to evaluate the economical aspect of CIN treatment including associated pregnancy complications by comparing both methods., Materials and Methods: We developed model treatment pathways for both conisation procedures and PDT using HAL. Thereafter, we calculated total costs for both treatment pathways including necessary re-treatments or alternative treatments. The estimated impact of conisation-related cervical insufficiency, prematurity, perinatal morbidity and life-long disability were determined. The total additional costs per conisation due to perinatal morbidity were calculated., Results: The total cost of treatment for CIN with a conisation procedure alone was 1,473 €, whereas the PDT procedure alone accounted for 1,386 €, based of assumptions of a 50% re-PDT rate, a 70% response rate and costs of 500 € for the PDT intervention itself. We computed 71, 144 and 545 newborns born prematurely due to conisation procedures <28, between 28 and <32 and between 32 and <37 weeks of gestation, leading to 18, 24 and 65 cases of severe, moderate and mild life-long disability. The attributable additional amount of maternofetal morbidity discounted by 3% for 7 years was 573 € per conisation. The total costs for a conisation therefore added up to 2,046 €, the total costs per treatment with PDT given the above-mentioned assumptions were 1,558 €., Conclusion: For Germany, PDT has the potential to be a cost-effective treatment for high-grade CIN compared to conisation procedure. Most important, the increased perinatal morbidity, perinatal mortality and associated costs after conisation procedures are significant and may be reduced by the implementation of PDT in CIN treatment., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose of Review: Reduce the burden of follow-up for patients and healthcare providers in noninvasive bladder cancer (NIBC). The evolution of intraoperative tumor detection, imaging modalities, urinary markers, and intravesical instillation regimens as a possibility to improve tumor eradication, enhance noninvasive tumor monitoring and thus to reduce costs is reviewed., Recent Findings: On the basis of current evidence, the recurrence and progression of patients with NIBC can significantly be improved by fluorescence-guided transurethral resection and perioperative chemoinstillation. Virtual cystoscopic modalities based on computed tomography or magnetic resonance imaging as well as a combination of urine biomarkers, which improve the sensitivity of conventional urine cytology, has the potential to reduce discomfort and pain associated with conventional cystoscopy. Recent meta-analyses have furthermore demonstrated that risk-adapted instillation regimens for immediate, induction and maintenance therapy using immuno-instillation and chemoinstillation therapy improve significantly recurrence-free and progression-free survival rates., Summary: Emerging technologies in the field of tumor visualization in combination with urinary markers and effective instillation regimens can significantly reduce the risk of recurrence and progression in the long-term whilst providing less patient discomfort and simplifying the follow-up in patients of NIBC.

Purpose: The purpose of this study was to evaluate the cost effectiveness of pegaptanib sodium and ranibizumab injections compared with photodynamic therapy (PDT) with verteporfin for the treatment of choroidal neovascularization secondary to age-related macular degeneration., Methods: The analyses were performed using outcomes data from the pivotal trials for each treatment and the medicare reimbursable costs for each treatment and associated medical procedures. A multistate transition model with 3-month cycles was created to compare incremental medical costs associated with pegaptanib or ranibizumab versus PDT for patients with starting vision of 20/40, 20/80, and 20/200 Snellen equivalent., Results: Two-year medical treatment costs ranged from $3,100 to $54,100 depending on treatment and lesion type. Photodynamic therapy was less costly and more effective than pegaptanib for predominantly classic and minimally classic lesions. Ranibizumab was not only more effective but also more costly than PDT for all lesion types., Conclusion: Compared with PDT, pegaptanib is inferior in both cost and effectiveness, whereas ranibizumab has a greater effectiveness. Because ranibizumab does not meet 1 of the common thresholds for being considered cost effective (<$50,000 per quality-adjusted life year), there is rationale to seek other therapies that are more cost effective.

Objective: To assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC), and urine biomarkers [fluorescence in situ hybridisation (FISH), ImmunoCyt, NMP22] and cytology for the detection and follow-up of bladder cancer., Data Sources: Major electronic databases including MEDLINE, MEDLINE In-Process, EMBASE, BIOSIS, Science Citation Index, Health Management Information Consortium and the Cochrane Controlled Trials Register were searched until April 2008., Review Methods: A systematic review of the literature was carried out according to standard methods. An economic model was constructed to assess the cost-effectiveness of alternative diagnostic and follow-up strategies for the diagnosis and management of patients with bladder cancer., Results: In total, 27 studies reported PDD test performance. In pooled estimates [95% confidence interval (CI)] for patient-level analysis, PDD had higher sensitivity than WLC [92% (80% to 100%) versus 71% (49% to 93%)] but lower specificity [57% (36% to 79%) versus 72% (47% to 96%)]. Similar results were found for biopsy-level analysis. The median sensitivities (range) of PDD and WLC for detecting lower risk, less aggressive tumours were similar for patient-level detection [92% (20% to 95%) versus 95% (8% to 100%)], but sensitivity was higher for PDD than for WLC for biopsy-level detection [96% (88% to 100%) versus 88% (74% to 100%)]. For more aggressive, higher-risk tumours the median sensitivity of PDD for both patient-level [89% (6% to 100%)] and biopsy-level [99% (54% to 100%)] detection was higher than those of WLC [56% (0% to 100%) and 67% (0% to 100%) respectively]. Four RCTs comparing PDD with WLC reported effectiveness outcomes. PDD use at transurethral resection of bladder tumour resulted in fewer residual tumours at check cystoscopy [relative risk, RR, 0.37 (95% CI 0.20 to 0.69)] and longer recurrence-free survival [RR 1.37 (95% CI 1.18 to 1.59)] compared with WLC. In 71 studies reporting the performance of biomarkers and cytology in detecting bladder cancer, sensitivity (95% CI) was highest for ImmunoCyt [84% (77% to 91%)] and lowest for cytology [44% (38% to 51%)], whereas specificity was highest for cytology [96% (94% to 98%)] and lowest for ImmunoCyt [75% (68% to 83%)]. In the cost-effectiveness analysis the most effective strategy in terms of true positive cases (44) and life-years (11.66) [flexible cystoscopy (CSC) and ImmunoCyt followed by PDD in initial diagnosis and CSC followed by WLC in follow-up] had an incremental cost per life-year of over 270,000 pounds. The least effective strategy [cytology followed by WLC in initial diagnosis (average cost over 20 years 1403 pounds, average life expectancy 11.59)] was most likely to be considered cost-effective when society's willingness to pay was less than 20,000 pounds per life-year. No strategy was cost-effective more than 50% of the time, but four of the eight strategies in the probabilistic sensitivity analysis (three involving a biomarker or PDD) were each associated with a 20% chance of being considered cost-effective. In sensitivity analyses the results were most sensitive to the pretest probability of disease (5% in the base case)., Conclusions: The advantages of PDD's higher sensitivity in detecting bladder cancer have to be weighed against the disadvantages of a higher false-positive rate. Taking into account the assumptions made in the model, strategies involving biomarkers and/or PDD provide additional benefits at a cost that society might be willing to pay. Strategies replacing WLC with PDD provide more life-years but it is unclear whether they are worth the extra cost.

Background: Actinic keratosis (AK) is caused by chronic exposure to UV radiation (sunlight). First-line treatments are cryosurgery, topical 5-fluorouracil (5-FU) and topical diclofenac. Where these are contraindicated or less appropriate, alternatives are imiquimod and photodynamic therapy (PDT)., Objective: To compare the cost effectiveness of imiquimod and methyl aminolevulinate-based PDT (MAL-PDT) from the perspective of the UK NHS., Methods: A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost effectiveness over 1 year. The model simulated patients who were in secondary care, who had four to nine AK lesions, and for whom cryosurgery, 5-FU and diclofenac were contraindicated or considered less appropriate., Results: Over 1 year, imiquimod cost £174 less than MAL-PDT (year 2006 values) but resulted in 0.005 fewer QALYs gained. The incremental cost-effectiveness ratio (ICER) of MAL-PDT over imiquimod was £34,576. In the probabilistic sensitivity analysis, there was a 75% probability that imiquimod was cost effective compared with MAL-PDT at a threshold of £20,000 per QALY gained, falling to 73% at £30,000., Conclusions: Imiquimod may be the more cost-effective treatment at conventional cost-effectiveness thresholds. A direct head-to-head study of MAL-PDT versus imiquimod is required to reduce uncertainty.

Purpose: To report (1) the costs of verteporfin photodynamic therapy (VPDT) in routine treatment of neovascular age-related macular degeneration (nAMD), (2) the relationship between health and social service costs and best-corrected visual acuity (BCVA), (3) the cost-effectiveness of VPDT versus a best supportive care (BSC) group who were assumed to have no active treatment, and (4) lessons for future cost-effectiveness analyses (CEAs)., Design: The CEA of VPDT versus BSC that uses health-related quality of life (HrQoL), resource use, and visual acuity data from the United Kingdom (UK) VPDT Cohort Study., Participants: Data on VPDT use were collected from patients attending 45 ophthalmology provider units in the UK National Health Service, 15 units collected data on self-reported use of services., Methods: Incremental costs of VPDT versus BSC were calculated from treatment costs, change in cost associated with declining BCVA, and difference in BCVA previously attributed to VPDT. Similarly, incremental quality-adjusted life years (QALYs) were calculated from change in HRQoL associated with declining BCVA, giving an incremental cost per QALY of VPDT versus BSC over 2 years., Main Outcome Measures: Incremental costs (UK pounds [ pound]; United States dollars [$]); incremental QALYs; costs per QALY., Results: The treatment costs of VDPT were pound 3026 ($4544) in year 1 and pound 845 ($1269) in year 2. For patients who used services, a 5-letter decrease in BCVA was associated with an increase in annual costs of approximately pound 110 ($165; 95% confidence intervals, approximately pound 48 [$72] to pound 174 [$261]). The incremental costs and QALYs for VPDT were pound 3514 ($5276) and 0.021, respectively, giving incremental costs per QALY gained of pound 170000 ($255000)., Conclusions: Verteporfin photodynamic therapy is unlikely to be cost effective for patients with nAMD. This article provides realistic estimates of VPDT costs and the costs associated with declining vision. Future studies can follow this approach to assess accurately the cost effectiveness of new interventions for nAMD.

Background: Basal cell carcinoma (BCC) is the most common form of skin cancer worldwide. Different treatment options exist. The efficacy of photodynamic therapy with methyl aminolevulinate (MAL-PDT) has been established in several randomized controlled trials (RCTs). Real life data can differ greatly from data derived from randomized controlled trials (RCTs)., Objectives: To describe the results of a Belgian observational study concerning superficial BCC (sBCC) vis-a-vis clinical and health economic outcomes in order to evaluate the real-life practice of MAL-PDT., Methods: This study was a prospective, single-arm, open study conducted at eight dermatological institutions during six months after the first MAL-PDT treatment. Eligible patients had to present with lesions, suitable for MAL-PDT according to Belgian reimbursement criteria. Resource use was collected during the study period. Clinical Response (CR) and Cosmetic Outcome (CO), as well as cost of care were evaluated. A subset analysis of patients with sBCC only was conducted., Results: Ninety patients were identified for the analysis (mean age 65 years; 61% female). The mean number of lesions per patient was 1.6, mostly located on the face, the back and the chest. For the entire period, the mean number of visits to a dermatologist was 4 per patient including two MAL-PDT sessions. The average, cumulative amount of MAL used per treatment was 1,256 mg. Two patients experienced adverse events at the application site, none of them serious; all resolved completely. The CR rate was 89% at the end of the study. The CO was "excellent" or "good" in 96% of the patients. Total cost of care was Euro 289 ($414 U.S.) per patient. Cost per lesion was Euro 195 ($280 U.S.)., Conclusion: The results from the real-life practice study confirm the efficacy found in prior, prospective randomized trials. About four visits and less than one tube of MAL are needed for the full treatment of sBCC in one patient.

Actinic keratoses (AK) commonly occur as lesions, in sun-exposed areas. Various treatment modalities exist for their removal. We assessed the cost-effectiveness in 2007 of topical treatments (5-fluorouracil, imiquimod) and photodynamic therapy with methyl aminolevulinate (MAL-PDT) for AK under the perspective of the UK National Health Service (NHS) in England and Wales over two lines of treatment. We used a decision tree analytical approach. Efficacy data were taken from published trial literature for two investigator-assessed outcomes: 'complete clinical response' and 'excellent cosmetic outcome'. MAL-PDT at first line followed by various second-line treatments provided the greatest probability of complete clinical response (91.7%), but MAL-PDT at first line followed by further MAL-PDT as the second-line treatment provided the greatest probability of excellent cosmetic outcome (73.6%). The cost of MAL-PDT was 437 pounds sterling after two lines of treatment if MAL-PDT was that second-line treatment or 418 pounds sterling if various treatments were offered at second line. The probabilistic analysis produced consistent results. Based on this model, the costs and effectiveness of MAL-PDT in the UK NHS compare well with other treatments for AK.

Aims: To assess effectiveness, cost, and cost-effectiveness of ranibizumab versus the current medical practices of treating age-related macular degeneration in France., Methods: A simulation decision framework over 1 year compared ranibizumab versus the usual care using two effectiveness criteria: the "visual acuity improvement rate" (greater than 15 letters on the ETDRS scale) and the "rate of legal blindness avoided". Two decision trees included various sequences of current treatments, with or without ranibizumab., Results: Ranibizumab appeared significantly more effective than the usual care (p < 0.001), providing greater treatment success rate of visual acuity improvement (48.8% versus 33.9%). The cost of the ranibizumab strategy was higher (9,123 euros over 1 year for ranibizumab versus 7,604 euros for the usual care) but the average cost-effectiveness was lower--18,721 euros/success for ranibizumab versus 22,543 euros/success for usual care (p < 0.001). Considering the "legal blindness avoided" success criterion, the ranibizumab strategy appeared significantly more effective (p < 0.001), providing greater treatment success rate for of legal blindness avoided than usual care (99.7% versus 93.1%) although it was more expensive (9,196 euros over 1 year for ranibizumab versus 5,713 euros for the usual care)., Conclusion: Ranibizumab significantly improved the rate of visual acuity improvement and reduced the rate of legal blindness. Ranibizumab appeared significantly more cost-effective than the usual treatments in terms of visual acuity improvement.

Clinical trials have shown that photodynamic therapy using methyl aminolevulinate (MAL-PDT) is an effective treatment for actinic keratosis (AK), and nodular and superficial basal cell carcinoma (nBCC and sBCC) unsuitable for other available therapies. Economic evaluation models have shown that it is a cost effective intervention as well. The objectives of this prospective, observational, one arm study were (i) to verify in a real-life practice study the results obtained in previous clinical trials with MAL-PDT in the treatment of AK, nBCC and sBCC; (ii) to calculate the real-life cost of treatment and validate predictions from an economic evaluation model. Patients with AK and/or BCC were selected according to Belgian reimbursement criteria for treatment with MAL-PDT. Clinical response, cosmetic outcome and tolerability were assessed. MAL-PDT cost was calculated and compared to published model cost data. Data were collected from 247 patients (117 AK, 130 BCC). A complete clinical response was obtained for 83% of AK (85/102) and BCC (97/116) patients. A good or excellent cosmetic outcome was obtained for 95% of AK patients and 93% of BCC patients. Tolerability was good: only 2 patients withdrew for adverse events. Clinical results were similar to previous studies. Total cost of care per patient was euro 381 for AK, euro 318 for nBCC, and euro 298 for sBCC. Total cost per lesion was euro 58 for AK (identical to model prediction), euro 316 for nBCC and euro 178 for sBCC (both within 20% of model prediction). The clinical results of MAL-PDT in this real-life practice study confirm those demonstrated in previous clinical trials. Costs calculated from this study confirm predicted cost-effectiveness in the original model for MAL-PDT in the management of AK and BCC.

Approximately 18,000 new cases of urothelial cancer of the bladder occur annually, making it the most frequent urogenital neoplasia representing nearly 4% of all malignomas. Tumor stage defines two subgroups requiring specific therapeutic approaches and implying distinct prognoses. Non-muscle-invasive urothelial cancer recurs frequently and occasionally progresses to muscle-invasive stages. Remnant tumor after initial resection is seen as one major factor in high recurrence rates. Although photodynamic diagnostics improving detection and increasing recurrence-free survival has been introduced to broad application, it has yet not been established as standard procedure. This article reviews the current literature and discusses controversial aspects.

Aims: To re-evaluate the cost-effectiveness of photodynamic therapy with verteporfin (Visudyne, Novartis AG, Switzerland) in patients with predominantly classic and classic choroidal neovascularization (CNV) owing to age-related macular degeneration (AMD), using new evidence on the impact of contrast sensitivity on health status., Method: A health economic model is used to synthesise the evidence on contrast sensitivity and treatment rates from the TAP Investigation with health state utilities and costs. Impairment of visual function is estimated using a Markov model to predict transitions between states of contrast sensitivity. Each state is associated with costs and a health state utility. Total expected costs and benefits for a cohort of patients over a defined number of cycles are calculated. The expected health state utility for each disease state was estimated using results from a study of 209 patients with AMD in Sheffield. The model includes the costs associated with treatment and monitoring in the verteporfin treatment arm and costs offset by delaying the deterioration of visual function., Results: Beyond 3 years, the annual costs of the verteporfin arm are estimated to be less than the annual costs of the control arm, owing to the cost associated with higher blindness prevalence in the control arm. Over time, the results show that both the incremental utility and cost decreases. By 10 years, the estimated incremental cost-effectiveness is approximately pound20 996 per Quality-Adjusted Life Years., Conclusion: The results of this study suggest that the verteporfin therapy in the treatment for patients with predominantly classic and classic CNV owing to AMD is encouraging.

Objectives: Age-related macular degeneration is the leading cause of legal blindness in older people. Choroidal neovascularization (CNV) is treatable with photodynamic therapy with verteporfin (PDT) but is expensive. The aim of this study was to assess the cost-effectiveness of PDT in routine clinical practice in Switzerland., Materials and Methods: A Markov model was used to analyze the costs of PDT in routine clinical practice. It described patients moving between good or impaired vision (visual acuity [VA]>0.1) and highly impaired vision (VA<0.1). Costs for PDT were based on the results of the Donati open-labeled prospective clinical study. Costs for medical and social management of AMD patients were defined according to Grainer's study., Results: The cost of PDT varied from 8,800 to 10,969 euros/patient/year. Ninety percent of the patients retained a VA > or =0.1. Health costs saved by keeping patients from moving to the highly impaired vision group was 4,248 euros/patient/year. Incremental costs per vision-year saved varied from 8,239 to 10,271 euros. Cost per quality-adjusted life year (QALY) gained at 5 years was 65,150 euros., Discussion: PDT was found to be moderately cost-effective in Switzerland. The longer the follow-up, the more cost-effective Visudyne was. Cost-effectiveness is a country-dependent assessment and analyses should be done for each health care system., Conclusion: PDT was found to be cost-effective in Switzerland (category C of Laupaci's classification).

Background: Age-related macular degeneration (AMD) is characterized by loss of central vision and is the leading cause of blindness among persons over the age of 50 years in Canada. The wet form of AMD has 3 subtypes-occult, minimally classic, and predominantly classic. Photodynamic therapy (PDT) with verteporfin is indicated only for the category of predominantly classic wet AMD. Currently, there are no treatments available for the other AMD subtypes. Pegaptanib sodium was the first pharmacologic therapy approved in Canada for the treatment of subfoveal wet AMD regardless of subtype., Objective: The aim of this study was to examine the cost-effectiveness of pegaptanib versus PDT with verteporfin and versus standard care for the treatment of subfoveal wet AMD in patients aged 65 years in Canada., Methods: A Markov model based on visual acuity in the better-seeing eye was developed. Clinical efficacy was taken from the clinical trials. Costs of treatment, comorbidities (eg, depression, fractures, need for assisted living), vision rehabilitation, visual aids, and adverse events were considered. Costs, utilities, and mortality were estimated from data from the available published literature. Costs were reported in 2004 Canadian dollars, and costs and outcomes were discounted at 3% per annum. Lifetime costs, quality-adjusted life-years (QALYs), and vision years gained (VYGs) were estimated. Sensitivity analyses were performed to determine model robustness., Results: Patients who received pegaptanib experienced more QALYs gained (4.17) and VYGs (3.83) compared with patients who received PDT (3.87 and 3.01, respectively) or standard care (3.96 and 3.26). Mean total costs per patient were greater in patients who received pegaptanib compared to those who received PDT or standard care ($20,016 vs $15,345 or $7669, respectively). The incremental cost per QALY in patients receiving pegaptanib compared to those receiving PDT was $49,052 and $59,039 for patients receiving pegaptanib versus standard care. The incremental cost per VYG was $20,401 and $21,559 with pegaptanib versus PDT and standard care, respectively. Sensitivity analyses found that the model was relatively robust to changes in various model parameters., Conclusion: The results of this analysis suggest that in Canada, pegaptanib is a cost-effective treatment for subfoveal wet AMD in elderly patients, regardless of lesion subtype, compared to PDT with verteporfin and to standard care.

Objective: To perform a value-based medicine analysis of clinical trials that evaluate the interventions of laser photocoagulation, intravitreal pegaptanib therapy, and photodynamic therapy (PDT) with verteporfin for the treatment of classic subfoveal choroidal neovascularization., Design: Reference case cost-utility analysis using value-based medicine principles, which use patient-based utility values and standardized, input variable criteria., Participants: Data from participants in the Macular Photocoagulation Study, Pegaptanib for Neovascular Age-Related Macular Degeneration Study, and the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study., Methods: Visual data were converted to a value-based format using time tradeoff utility analysis values from patients with macular degeneration. Costs were obtained from 2005 Medicare data. Outcomes (quality-adjusted life-years [QALYs]) and costs were discounted at a 3% annual rate., Main Outcome Measures: Interventional QALYs gained, percent improvement in quality of life, and dollars spent per QALY gained., Results: Laser photocoagulation confers a 4.4% (P = 0.03 versus pegaptanib therapy) improvement in quality of life for the reference case, whereas pegaptanib therapy confers a 5.9% improvement and PDT confers an 8.1% (P = 0.0002 versus pegaptanib therapy) improvement. The cost-utility associated with laser photocoagulation is $8179, that for pegaptanib therapy is $66978, and that for PDT is $31544. All sensitivity analyses remain within the conventional standards of cost-effectiveness., Conclusions: Photodynamic therapy confers greater patient value than intravitreal pegaptanib therapy and laser photocoagulation for the treatment of classic subfoveal choroidal neovascularization. Despite the fact that laser photocoagulation is the most cost-effective intervention, both PDT and pegaptanib therapy deliver greater value, and thus are both preferred over laser photocoagulation. Using an economic measure, photodynamic therapy is the preferred treatment among these 3 interventions.

Background: Various effective therapeutic options are currently available for the treatment of actinic keratosis (AK) and basal cell carcinoma (BCC), but none is perfect. Poor cosmesis resulting from surgical procedures and skin irritation induced by topical agents remain significant problems., Objectives: To evaluate the cost-effectiveness of a recent approach, methyl aminolaevulinate-based photodynamic therapy (MAL-PDT; Metvix; Galderma, Lausanne, Switzerland) in AK and BCC., Methods: A medical decision tree was developed for simulation of all possible outcomes associated with the medical decision to apply MAL-PDT or a comparator. The time horizon was 1 year for AK and 5 years for BCC. The comparators were cryotherapy in AK and excision surgery in BCC. Clinical data for the model were obtained from the literature. Data on medical management resulted from a Delphi panel performed among 12 Belgian dermatologists. Based on the model, the cost per full responder was calculated, whereby a responder was defined as a patient with all lesions clinically responding and showing an excellent cosmetic result., Results: MAL-PDT is a more expensive treatment compared with cryotherapy for AK. However, the cost per full responder is comparable with cryotherapy (euro363 and euro379, respectively). Incremental cost per extra full responder is euro401. Incremental cost per full responder is euro469 for nodular BCC and euro251 for superficial BCC, both compared with excision surgery., Conclusions: The results suggest that MAL-PDT is a cost-effective intervention in AK taking a 1-year time horizon, if society is willing to pay euro1.50 per day of response, and that MAL-PDT is better value for money than excision in BCC, taking a 5-year time horizon.

The prevalence of neovascular age-related macular degeneration (AMD) is expected to increase significantly during the next 20 years. New treatment alternatives to laser photocoagulation are on the horizon - the first of these, photodynamic therapy (PDT) with verteporfin, was approved by the US FDA in 2000. In this article we present a preliminary risk-benefit assessment of verteporfin in AMD, focusing on the landmark randomised, double-blind, placebo-controlled studies. The TAP (Treatment of Age-related macular degeneration with Photodynamic therapy) trial established the efficacy of PDT for classic subfoveal neovascularisation in AMD at 2 years follow-up. The VIP (Verteporfin in Photodynamic therapy) study concentrated on subfoveal occult-only lesions not included in the TAP study. After 2 years, treated eyes were less likely to experience visual loss. Exploratory analyses of TAP and VIP suggest that lesion size is a more significant predictor of the treatment benefit than either lesion composition or visual activity. The VIM (Visudyne in Minimally classic) trial altered the standard PDT light fluence rate in the treatment of subfoveal minimally classic lesions. This trial again demonstrated a beneficial effect for those receiving treatment with PDT. The VIO (Visudyne in Occult) trial, evaluating PDT in occult-only lesions as a confirmatory study of the VIP trial, did not achieve its primary end-point at 2 years. Further analyses are pending.PDT with verteporfin has an excellent safety profile that has been established with >1 million treatment applications. Cost-effectiveness data are limited but suggest that PDT may be a cost-effective treatment modality. Other FDA-approved treatments (pegaptanib, ranibizumab and bevacizumab) for neovascular AMD are discussed, as well as investigational substances such as anecortave acetate.

Purpose: To assess the value conferred by photodynamic therapy (PDT) and the cost-utility of PDT for the treatment of classic, subfoveal choroidal neovascularization associated with age-related macular degeneration (ARMD)., Design: Average cost-utility analysis utilizing clinical trial data, patient-based time tradeoff utility preferences, and a third party insurer cost perspective., Methods: Five-year visual acuity data from the TAP (Treatment of Age-related Macular Degeneration With Photodynamic Therapy) Investigation were modeled into a 12-year, value-based, reference case, cost-utility model utilizing year 2004 Medicare costs and an outcome of dollar/QALY (dollars/quality-adjusted life-year). Discounting of outcomes and costs using net present value analysis with a 3% annual rate was performed as recommended by the Panel for Cost-Effectiveness in Health and Medicine., Results: PDT with verteporfin (Visudyne) dye for classic subfoveal choroidal neovascularization confers an 8.1% quality of life (value) improvement over the 12-year life expectancy of the reference case, while during the last 8 years the value improvement is 9.5%. The average cost-utility of the intervention is dollar 31,103/QALY (quality-adjusted life-year). Extensive one-way sensitivity analysis values range from dollar 20,736/QALY if treatment efficacy is increased by 50% to dollar 62,207 if treatment efficacy is decreased by 50%, indicating robustness of the model., Conclusions: PDT using verteporfin dye to treat classic subfoveal choroidal neovascularization is a very cost-effective treatment by conventional standards. The marked improvement in cost-effectiveness compared with a previous report results from the facts that the treatment benefit increasingly accrues during 5 years of follow-up while the number of yearly treatments diminishes markedly during that time.

Bladder cancer is a frequent disease and represents the second most common genitourinary neoplasm. Although many aspects of the management of superficial bladder cancer are now well established, significant challenges remain, which influences patient outcome. Early detection and treatment of recurrent disease is required to optimize bladder preservation, reduce patient morbidity, and increase quality of life and survival. Fluorescence endoscopy, often referred to as 'photodynamic diagnosis' (PDD), with intravesical application of photosensitizing agents, has been developed to enhance the early detection of bladder cancer. There is growing evidence that PDD using 5-aminolaevulinic acid (ALA), hexyl-ALA ester or hypericin enhances the detection of bladder cancer, particularly of high-grade flat lesions. Furthermore, transurethral resection of bladder tumour under fluorescence guidance reduces the risk of recurrent tumours. However, the impact on the progression of disease remains unclear and must be investigated in prospective randomized trials.

Objective: Health economic models can assist policy-makers in determining the value of novel treatments from the viewpoint of society. In this context, value is defined as the benefit of treatment, given its cost. A new treatment for wet age-related macular degeneration (AMD), juxtascleral administration of anecortave acetate, 15 mg for depot suspension (Retaane), is now in a late-phase clinical trial. In a theoretical analysis, we sought to determine the cost at which this treatment might offer economic value to society, using incremental cost-effectiveness ratios (ICERs)., Methods: A series of 1-year cost-utility models was created for the investigational treatment and standard treatment (photodynamic therapy [PDT] with verteporfin [Visudyne]). Value to society was defined in terms of theoretical associated ICERs (in US dollars): $100,000 per quality-adjusted life-year (QALY), $50,000/QALY, $20,000/QALY and $0/QALY, the point of economic indifference. Models were created from the societal perspective and included a patient-derived utility assessment involving regression equations to estimate time trade-off preferences, event probabilities derived from a randomized clinical trial comparing the safety and efficacy of anecortave administration and PDT with verteporfin, decision analysis and relevant costing information., Results: An ICER of $100,000/QALY would be associated with an anecortave cost of $3022/vial, an ICER of $50,000/QALY with an anecortave cost of $2986/vial and an ICER of $20,000/QALY with an anecortave cost of $2964/vial. The point of economic indifference between anecortave administration and standard therapy would occur with an anecortave cost of $2950/vial., Interpretation: In theory, an anecortave cost of $2986/vial is associated with an ICER of $50,000/QALY, the threshold used by many health technology assessment and reimbursement agencies.

Objectives: In Ontario, Canada, in a cohort of all people initially aged 50-54 years, modeling whether the Age-Related Eye Disease Study (AREDS) antioxidant supplementation for stage 3 and 4 AMD would decrease the costs of photodynamic treatment with Visudyne., Perspective: Third party payer, the Ontario Health Insurance Plan., Methods: Using reported risk reductions, prevalence data by age and sex from the Beaver Dam studies, and yearly costs: AREDS 182.50 Canadian dollars, potential savings were calculated as the difference or incremental cost between the estimated medical costs for the untreated cohort of 17,000 Canadian dollars for Visudyne treatment of individuals with neovascularization and the same cohort if stage 3 and 4 AMD patients were treated with antioxidants, decreasing progression to neovascularization. Different scenarios were explored for sensitivity analysis of direct cost savings., Results: For the Ontario cohort of approximately 788,000 aged 51-55 years in 2001, for photodynamic therapy of the untreated cohort, modeled costs were 1.7 billion Canadian dollars. AREDS treatment costs would be 513 million Canadian dollars. AREDS would reduce photodynamic therapy costs, a net saving of 431 million Canadian dollars, a saving of 547 Canadian dollars per person in the total cohort, or 6,753 Canadian dollars per stage 3 and 4 patient treated. To explore the sensitivity of this model to AMD incidence rather than prevalence data, Framingham incidence data were incorporated in the model: net savings of 70.3 million Canadian dollars were modeled using Framingham incidence data., Conclusion: Under reasonable assumptions, if the case progresses to wet AMD (1) AREDS with Visudyne is less expensive than Visudyne alone in every five-year time period for the cohort that is age 50-54 right now until they become 75-79; thus, the lifetime cost is lower; (2) AREDS with Visudyne yields more QALYs than Visudyne alone in every five-year interval; (3) under all but the most extreme assumptions, the conclusions reached are robust. Even when AREDS costs a little more, it yields more QALYs at a reasonable cost per QALY. Thus, AREDS antioxidant supplementation appears to be a dominant strategy for macular degeneration. Applied to the whole Canadian population, the potential medical cost savings for Visudyne treatment of neovascular AMD are 5.6 billion Canadian dollars in direct costs. These values would be tenfold higher for the USA, because of the currency and population size differences.