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Economic Evaluation of Factorial Trials: Cost-Utility Analysis of the Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes 2 × 2 × 2 Factorial Trial of Atorvastatin, Omega-3 Fish Oil, and Action Planning.

ABSTRACT: OBJECTIVES:We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective. METHODS:The Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions. RESULTS:We observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ?99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20?000/QALY threshold. CONCLUSIONS:Atorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20?000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation.

SUBMITTER: Dakin HA

PROVIDER: S-EPMC7537832 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Economic Evaluation of Factorial Trials: Cost-Utility Analysis of the Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes 2 × 2 × 2 Factorial Trial of Atorvastatin, Omega-3 Fish Oil, and Action Planning.

Dakin Helen A HA Farmer Andrew A Gray Alastair M AM Holman Rury R RR

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research 20200818 10

<h4>Objectives</h4>We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.<h4>Methods</h4>The Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 d ...[more]

PMID: 33032778

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Project description:Background:Globally, it is known that HIV-infected pregnant women are prone to depressive symptoms. Research evidences also suggest that nutrient deficiencies may enhance the depressive illness, and that fish oil omega-3 fatty acids may alleviate the depressive symptoms. The aim of this study was to assess the effect of fish oil omega-3 eicosapentaenoic acid-rich supplements on depressive symptoms among HIV-seropositive pregnant women. Trial design:A randomized double-blinded controlled trial with two parallel groups was conducted. The intervention group received fish oil omega-3 of 3.17 g (eicosapentaenoic acid?=?2.15 g; docosahexaenoic acid?=?1.02 g) per day for 8 weeks, while the control group received soybean oil for a similar period. Method:Participants were HIV-seropositive pregnant women who were enrolled in prevention of mother-to-child transmission programs and attending antenatal clinics at selected Nairobi city county's health facilities. Recruitment was done from health records of HIV-infected pregnant women. Data analysis followed per-protocol analysis. Participants who completed the 8-week trial were included in the analysis of covariance statistical model with omega-3 as main effect. The covariates in the change in BDI-II depressive symptom score outcome were baseline characteristics and nutrient adequacy. Results:282 participants were recruited 109 randomized to fish oil, and 107 to soybean oil. Completion rate was 86/109 (78.9%) and 96/107 (89.7%) respectively. At the end of week-8 of follow up most participants in both arms had mild depressive symptoms 82/86 (95.3%) in the Fish oil group and 94/96 (97.9%) in the Soybean oil group. The difference in effect between the intervention and control group was not statistically significant (1.01 (95% CI -?0.58 to 2.60), p?=?0.21). Conclusion:Fish oil omega-3 with a daily dosage of 3.17 g (eicosapentaenoic acid?=?2.15 g; docosahexaenoic acid?=?1.02 g) appears to provide no added benefit in reduction of the symptoms of depression in HIV-infected pregnant women.Trial Registration Clinical Trial Registry: NCT01614249. Registered on June 5, 2012. https://clinicaltrials.gov/ct2/show/NCT01614249.

Project description:BACKGROUND:N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD). MATERIALS AND METHODS:The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD. RESULTS:Twenty-four patients with claudication received 4.4 g/d of fish oil or placebo for 3 mo. Outcomes measured included high-sensitivity C-reactive protein levels, the omega-3 index, endothelial function as measured via flow-mediated vasodilation, walking impairment questionnaire, and a 6-min walk test. Plasma levels of specialized pro-resolving lipid mediators (SPMs) were measured by liquid-chromatography-tandem mass spectrometry. In patients treated with fish oil, the absolute mean omega-3 index significantly increased from baseline (fish oil: 7.2 ± 1.2%, P < 0.001; placebo: -0.4 ± 0.9%, P = 0.31; between-group P < 0.001). Furthermore, there were significant increases in several pathway markers of SPM biosynthesis, including several mono-hydroxyeicosapentaenoic acids and mono-hydroxydocosahexaenoic acids. We also observed significant increases in the SPM lipoxin A5 (fish oil: 0.57 ± 0.70 pg/mL, P = 0.05; placebo: 0.01 ± 0.38 pg/mL, P = 0.93; between-group P = 0.04) and resolvin E3 (fish oil: 154 ± 171 pg/mL, P = 0.04; placebo: 32 ± 54 pg/mL, P = 0.08; between-group P = 0.04). There were no significant changes in high-sensitivity C-reactive protein, flow-mediated vasodilation, walking impairment questionnaire, or 6-min walk test in the fish oil group. CONCLUSIONS:Fish oil increases SPMs in plasma of patients with PAD. Further studies are required to determine whether these early changes translate to clinical improvements in patients with PAD.

Project description:Sepsis plays an important role in acute gastrointestinal injury (AGI). Our research was designed to determine the effects of omega-3 fish oil (FO) in patients suffering from severe sepsis combined with AGI III, and the ability of FO to modulate immune function.Seventy-eight patients diagnosed with severe sepsis with AGI III and a need for mechanical ventilation were randomized to two groups. In the FO group, 50 g of long chain fatty acid soybean oil (n = 6) and 10 g of FO (n = 3) were administered as total parenteral nutrition (TPN). The control group was treated with 50 g of long chain fatty acid soybean oil without addition of FO to TPN.At baseline, there were no significant differences between the two groups. The 60-day mortality was lower in the FO group. Multiple factor logistic regression analysis revealed that intra-abdominal pressure (IAP) and abdominal infection were correlated with the FO intervention. The patients with abdominal infection demonstrated a lower mortality rate, fewer CD3 T lymphocytes, and fewer helper/inducer T lymphocytes in the FO group compared with the control group. After 7 days, the Marshall Score was lower in the FO group than in the control group.FO has positive effects in terms of improving the long-term prognosis of patients with severe sepsis with AGI III. Patients with a high IAP and abdominal infection might experience greater benefit from FO. This effect might be due, in part, to immunomodulation.Fish oil (FO) has positive effects in terms of improving the long-term prognosis of patients with severe sepsis with acute gastrointestinal injury Grade IIIPatients with a high intra-abdominal pressure and abdominal infection might experience greater benefit from FOThis effect might be due, in part, to immunomodulation. Abbreviations used: AGI: Acute gastrointestinal injury; FO: Fish oil; TPN: Total parenteral nutrition; IAP: Intra-abdominal pressure; ICU: Intensive Care Unit; MODS: Multiple organ dysfunction syndrome; TLR4: Toll-like receptor 4; DNR: Do Not Resuscitate; WGAP: Working Group of Abdominal Problem; EN: Enteral nutrition; BP: Low blood pressure; CRI: Catheter-related infection; PBS: Phosphate-buffered saline; ELFA: Enzyme-linked fluorescent assay; SD: Standard deviation; PUFAs: Polyunsaturated fatty acids; EPA: Eicosapentenoic acid; DHA: Docosahexaenoic acid.

Project description:Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), likely prevent cardiovascular disease, however their mechanisms remain unclear. Recently, the role of DNA damage in atherogenesis has been receiving considerable attention. Here, we investigated the effects of EPA and DHA on DNA damage in vascular endothelial cells to clarify their antiatherogenic mechanisms.We determined the effect of EPA and DHA on H2O2-induced DNA damage response in human aortic endothelial cells. Immunofluorescence staining showed that ?-H2AX foci formation, a prominent marker of DNA damage, was significantly reduced in the cells treated with EPA and DHA (by 47% and 48%, respectively). H2O2-induced activation of ATM, a major kinase orchestrating DNA damage response, was significantly reduced with EPA and DHA treatment (by 31% and 33%, respectively). These results indicated EPA and DHA attenuated DNA damage independently of the DNA damage response. Thus the effects of EPA and DHA on a source of DNA damage were examined. EPA and DHA significantly reduced intracellular reactive oxygen species under both basal condition and H2O2 stimulation. In addition, the mRNA levels of antioxidant molecules, such as heme oxygenase-1, thioredoxin reductase 1, ferritin light chain, ferritin heavy chain and manganese superoxide dismutase, were significantly increased with EPA and DHA. Silencing nuclear factor erythroid 2-related factor 2 (NRF2) remarkably abrogated the increases in mRNA levels of antioxidant molecules and the decrease in intracellular reactive oxygen species. Furthermore, EPA and DHA significantly reduced H2O2-induced senescence-associated ?-galactosidase activity in the cells (by 31% and 22%, respectively), which was revoked by NRF2 silencing.Our results suggested that EPA and DHA attenuate oxidative stress-induced DNA damage in vascular endothelial cells through upregulation of NRF2-mediated antioxidant response. Therefore omega-3 fatty acids likely help prevent cardiovascular disease, at least in part, by their genome protective properties.

Dataset Information

Economic Evaluation of Factorial Trials: Cost-Utility Analysis of the Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes 2 × 2 × 2 Factorial Trial of Atorvastatin, Omega-3 Fish Oil, and Action Planning.

Publications

Economic Evaluation of Factorial Trials: Cost-Utility Analysis of the Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes 2 × 2 × 2 Factorial Trial of Atorvastatin, Omega-3 Fish Oil, and Action Planning.

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