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ObjectiveTo establish how real-world evidence (RWE) has been used to inform single technology appraisals (STAs) of cancer drugs conducted by the National Institute for Health and Care Excellence (NICE).MethodsSTAs published by NICE from April 2011 to October 2018 that evaluated cancer treatments were reviewed. Information regarding the use of RWE to directly inform the company-submitted cost-effectiveness analysis was extracted and categorized by topic. Summary statistics were used to describe emergent themes, and a narrative summary was provided for key case studies.ResultsMaterials for a total of 113 relevant STAs were identified and analyzed, of which nearly all (96 percent) included some form of RWE within the company-submitted cost-effectiveness analysis. The most common categories of RWE use concerned the health-related quality of life of patients (71 percent), costs (46 percent), and medical resource utilization (40 percent). While sources of RWE were routinely criticized as part of the appraisal process, we identified only two cases where the use of RWE was overtly rejected; hence, in the majority of cases, RWE was accepted in cancer drug submissions to NICE.DiscussionRWE has been used extensively in cancer submissions to NICE. Key criticisms of RWE in submissions to NICE are seldom regarding the use of RWE in general; instead, these are typically concerned with specific data sources and the applicability of these to the decision problem. Within an appropriate context, RWE constitutes an extremely valuable source of information to inform decision making; yet the development of best practice guidelines may improve current reporting standards.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a strain of coronavirus that causes a respiratory illness known as COVID-19. COVID-19 is a pandemic affecting many countries globally.(1) As of 23rd July 2020, there have been 297,146 lab-confirmed cases of COVID-19 in the UK and 45,554 people who tested positive for the virus have died.(2) Patients with multiple myeloma (MM) are at a higher risk of contracting the virus and experiencing more severe outcomes.(3-6) The higher risk is driven by a compromised immune system, the use of immunosuppressive agents and patient characteristics aligning with key risk factors - patients with MM are often elderly and have multiple co-morbidities.(7) In light of the COVID-19 outbreak, NHS England and NICE have issued guidance to modify usual care to reduce patient exposure to COVID-19. For patients with cancer, NICE recommend delivering systemic anti-cancer treatment in different and less immunosuppressive regimens, different locations (ideally at home) or via another (less invasive and/or less resource intensive) route of administration where possible.(8)(9) The objective of this analysis is to explore the impact of switching patients from intravenous (IV) treatments requiring hospital administrations to subcutaneous (SC) or oral alternatives which can be administered at home or in an outpatient setting which reduces the patient's potential exposure to COVID-19. Methods: A decision tree model was developed in Microsoft Excel® (Figure 1). Patients enter the model and are assigned a probability of being treated; those that are treated are then assigned a probability of IV, SC or oral-based therapy. Based on the route of administration, patients are assigned a probability of contracting COVID-19 and, for those patients that do contract the virus, a probability of death from the virus is estimated. The model compares the outcomes from two identical decision trees: one informed by the pre-COVID-19 treatment pathway and one informed by the post-COVID-19 pathway. Model inputs, including COVID-19 inputs (e.g., number of active and diseased COVID-19 cases among patients with MM), have been informed by the literature and clinical opinion. Costs reflected in the model include: treatment of COVID-19, treatment for MM and administration of MM treatments. Scenario analyses explore lower and upper bounds for key inputs. Results are presented from a UK perspective and a 1-year time horizon (from model entry) is considered. Results: Per the model, treating patients with oral therapies is shown to reduce the number of COVID-19 cases and the number of COVID-19 deaths in patients with MM compared with IV- and SC-delivered therapies. These outcomes translate into cost savings driven by costs avoided in treating COVID-19. There was a limited difference in the costs of treating the underlying MM despite the switch. However, there were additional cost savings demonstrated through avoiding expensive and resource intensive administration appointments associated with IV therapies, and to a lesser extent SC therapies. The use of oral therapies has also aided the increase in telemedicine for routine appointments - scenarios exploring this demonstrate further savings. These results are driven by the perceived risk attached to each of the different routes of administration - scenario analyses demonstrated that assuming even the lower bound risk (an assumed additional risk of 10%) for IV therapies vs. oral therapies, a significant number of COVID-19 cases and deaths were avoided, and costs reduced. Conclusions: Changes to the treatment pathway for patients with MM in light of the COVID-19 pandemic aim to reduce the exposure to the virus for these patients. The model demonstrates that simply switching the route of administration can reduce the number of COVID-19 cases and deaths . This has important implications in avoiding severe outcomes, decreasing the spread of the virus and reducing the cost and resource use burden to the healthcare system. In addition, the model reflects potential efficiencies which may extend beyond the COVID-19 pandemic (e.g. telemedicine) to optimize clinical practice for patients with MM in the longer-term. Disclosures Cranmer: Takeda: Current Employment. Podkonjak:Takeda: Current Employment. Benson:Takeda: Current Employment. Dabora:Takeda: Current Employment. Jackson:Merck Sharp and Dohme: Honoraria; Chugai: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Roche: Honoraria.

Objective: To evaluate cost-effectiveness of brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma who have received autologous stem cell transplantation, from a Scottish healthcare payer perspective. Methods: A Microsoft Excel-based partitioned survival model comprising three health states (progression-free survival [PFS], post-progression survival, and death) was developed. Relevant comparators were chemotherapy with or without radiotherapy (C/R) and C/R with intent to allogeneic hematopoietic stem cell transplantation (alloSCT). Data were obtained from the pivotal phase II single-arm trial in 102 patients (SG035-0003; NCT00848926), a systematic literature review and clinical expert opinions (where empirical evidence was unavailable). PFS and overall survival for brentuximab vedotin were estimated using 5-year follow-up data from SG035-0003, and extrapolated using event rates observed for comparator treatments from published survival data. Resource use included drug acquisition and administration; alloSCT; treatment of adverse events; and long-term follow-up. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty. Results: In the base case, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin was £38,769 per quality-adjusted life year (QALY) vs C/R, whereas C/R with intent to alloSCT was dominated by brentuximab vedotin. ICERs for brentuximab vedotin generated by the deterministic sensitivity analysis ranged between £32,000–£54,000 per QALY. Including productivity benefits reduced the ICER to £28,881 per QALY. Limitations: Limitations include lack of comparative data from this single arm study and the heterogeneous population. Inconsistent baseline characteristic reporting across studies prevented complete assessment of heterogeneity and the extent of potential bias in clinical and cost-effectiveness estimates. Conclusions: Although the base case ICER is above the threshold usually applied in Scotland, it is relatively low compared with other orphan drugs, and lower than the ICER generated using a previous data cut of SG035-0003 that informed a positive recommendation from the Scottish Medicines Consortium, under its decision-making framework for assessment of ultra-orphan medicines.

19 Background: In 2015, the Scottish Medicines Consortium (SMC) made a positive recommandation for brentuximab vedotin (BV) in patients with relapsed or refractory (R/R) Hodgkin lymphoma (HL) who have received autologous stem cell transplantation (ASCT) based on 3-year follow-up data from the pivotal phase 2 single-arm trial (SG035-0003; NCT00848926). At 3-years, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin compared with chemotherapy +/- radiotherapy (C/R) was £43,731 per quality-adjusted life year (QALY). This study re-evaluated the cost-effectiveness analysis with 5-year follow-up data from the pivotal trial. Methods: A partitioned survival model was developed using a Scottish health system perspective over a lifetime time-horizon. Three health states were evaluated: progression-free survival (PFS), post-progression survival, and death. The relevant comparators were C/R, or C/R with intent to allogeneic stem cell transplantation. Clinical outcomes (PFS and overall survival [OS]) for BV were estimated based on data from the pivotal trial in 102 patients. A naïve comparison with the specified comparators was conducted using published survival data. ICERs were calculated with measures of the clinical outcomes, direct costs and QALYs. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the model. Results: The 5-year follow-up data reduced the base case ICER for BV from £43,731 to £38,769 per QALY versus C/R and increased the probability of cost-effectiveness. The variation in ICER for BV generated by the deterministic sensitivity analyses was also reduced resulting from reduced uncertainty in the estimation of long term clinical outcomes. Conclusions: This update has strengthened the cost-effectiveness evidence for BV in patients with R/R HL post-ASCT. The 5-year follow-up has reduced the uncertainty in the long term outcomes and reduced the ICER, which is low in comparison to other treatments for orphan diseases approved by UK agencies. BV may therefore represent a cost-effective treatment option for this patient group.

18 Background: Systemic anaplastic large cell lymphoma (sALCL) is a rare T-cell lymphoma. For patients who fail front-line therapy, outcomes are poor and there is no current defined standard of care. Brentuximab vedotin has demonstrated high objective response rates and is approved for patients with relapsed or refractory (R/R) sALCL. However, the cost-effectiveness of brentuximab vedotin compared with conventional chemotherapy has not been explored. Methods: A lifetime Excel-based partitioned survival model was used to compare survival outcomes from the pivotal phase-2 single-arm brentuximab vedotin trial of 58 R/R sALCL patients with good Eastern Corporative Oncology Group (ECOG) performance status after one or more prior therapies (SG035-0004); with 40 sALCL patients from a Canadian cancer registry receiving first-line conventional salvage chemotherapy (65% with ECOG 0 or 1) between 1980 and 2012 and followed for up to 20 years. Extrapolation of brentuximab vedotin survival after the trial period assumed the same rate of change as for conventional chemotherapy. A United Kingdom National Health Service perspective was adopted. Costs included drug acquisition and administration, and medical care for adverse events and pre- and post-progression. Utility values elicited by response and by progression, and disutilities associated with adverse events were applied to estimate quality-adjusted life years (QALYs). Results: The incremental cost-effectiveness ratio (ICER) for brentuximab vedotin was £35,390 per QALY gained versus conventional chemotherapy. ICERs were between £28,112 and £61,921 across a range of alternative model assumptions. Comparing only first-line salvage patients in both groups reduced the ICER to £26,766. Conversely, considering only patients with good ECOG performance status increased the ICER to £38,186. Using probabilistic sensitivity analysis, at willingness-to-pay of £38,000, the probability that brentuximab vedotin is cost-effective was > 50%. Conclusions: Brentuximab vedotin may represent a cost-effective intervention compared to conventional chemotherapy for this patient population with limited therapeutic options.

Abad, Gemino Henson (b. 1939) Abbas, Khwaja Ahmad (1914-87) Aboriginal literature (Australia) Aboriginal Literature (Canada) Aboriginal songs and narrative Aboud, James C. (b. 1956) Abrahams, Lionel (b. 1928) Abrahams, Peter (b. 1919) Abruquah, Joseph Wilfred (b. 1921) Achebe, Chinua (b. 1930) Acorn, Milton (1923-86) Adams, Arthur H. (1872-1936) Adams, Glenda (b. 1939) Adamson, Robert (b. 1944) Adcock, Fleur (b. 1934) Adewale, Toyin (b. 1969) Africa in Canadian Literature African Connections Afrika, Tatamkhulu (1920-2002) Agard, John (b. 1949) Ahmad, Sayeed (b. 1931) Aidoo, Ama Ata (b. 1942) Alexander, Meena (b. 1951) Alfon, Estrella D. (1918-83) ALI, AGHA SHADID (1949-2001) Ali, Ahmed (1910-94) Alkali, Zaynab (1955-?96) Alley, Rewi (1897-1987) Allfrey, Phyllis Shand (1915-86) Aluko, Timothy Mofolorunso (b. 1918) Amadi, Elechi (b. 1934) Amanuddin, Syed (1934-89) AMERINDIANS IN CARIBBEAN LITERATURE Anand, Mulk Raj (b. 1905) ANANTANARAYANAN, M. (b. 1907) Andersen, Johannes Carl (1873-1962) Anderson, Barbara (b. 1926) Anderson, Ethel Anderson, Jessica (b. 1923) Anggraeni, Dewi (b. 1945 ) Angira, Jared (b. 1947) anthologies (Australia) Anthologies (Canada) anthologies (East Africa) anthologies (Hong Kong) Anthologies (India) Anthologies (Malaysia and Singapore) anthologies (New Zealand) Anthologies (Pakistan) Anthologies (South Africa) anthologies (Sri Lanka) Anthologies (The Caribbean) anthologies (The Philippines) Anthologies (West Africa) Anthony, Frank Sheldon (1891-1927) Anthony, Michael (b. 1930) Antoni, Robert (b. 1958 ) Anyidoho, Kofi (b. 1947) Arcellana, Francisco (1916-2002) Archibald, Douglas Rupert (b. 1919) Arguilla, Manuel E. (1910-44) Armah, Ayi Kwei (b. 1939) Asare, Bediako (b. 1930) Ashton-Warner, Sylvia (1908-84) Astley, Thea (b. 1925) Atwood, Margaret (b. 1939) AUROBINDO, SRI (1872-1950) Australia Australia Council Australia in Canadian Literature in English Australian Eco-Novel Avison, Margaret (b. 1918) awards (Australia) awards (Canada) Awards (India) Awards (New Zealand) Awards (Singapore) Awards (South Africa) Awards (The Philippines) Awards (West Africa) Awoonor, Kofi Nyidevu (b. 1935) Ayyar, A. S. Panchapakesa (1899-1963) Badami, Anita Rau (b. 1961) Bail, Murray (b. 1941) Baird, Irene (1901-81) Baldwin, Shauna Singh (b. 1962) Ballantyne, David (1924-86) Bandele, Biyi (b. 1967) Bandler, Faith (b. 1918) Bangladesh Baranay, Inez Baratham, Gopal (1935-2002 ) Barker, Lady Mary Ann (1831-1911) Barnard, Marjorie Faith Bascom, Harold A. (b. 1951) Basu, Romen (b. 1923) Baugh, Edward Alston Cecil (b. 1936) Baughan, Blanche Edith (1870-1958) Bautista, Cirilo F. (b. 1941) Baxter, James Keir (1926-72) Beaglehole, John Cawte (1901-71) Bean, C. E. W. (1879-1968) Beaver, Bruce Bedford, Jean (b. 1946) Bekederemo, John Pepper Clark (b. 1935) Belgrave, Valerie (b. 1949) Ben-Abdullah, Mohammed (b. 1944) Bennett, Alvin Gladstone (b. 191

This new edition of the acclaimed Oxford Companion to Canadian Literature has been thoroughly updated with more than 350 new entries on new writers, new books, and extended entries on established authors. In keeping with the original, entries cover fiction, prose, poetry, and drama, prominent writers, literary magazines, publishers, and more general topics. All existing entries have been completely updated to reflect the most recent publications by writers included in the original edition. From The Apprenticeship of Duddy Kravitz to the Rebel Angles, Sandra Birdsell to Eric Wright, Caribbean-Canadian literature to War literature, this completely revised edition is not only an invaluable resource, but a browser's delight for anyone interested in Canadian literature.

Introduction Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), approved for the treatment of type 2 diabetes mellitus (T2DM). There currently exists no comparative data to support the use of alogliptin in combination with metformin (met) and sulfonylurea (SU). A decision-focused network meta-analysis (NMA) was performed to compare the relative efficacy and safety of alogliptin 25 mg once daily to other DPP-4 inhibitors as part of a triple therapy regimen for patients inadequately controlled on metformin and SU dual therapy. Methods A systematic literature review was conducted to identify published papers of randomized controlled trials (RCTs) that compared alogliptin with other DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) at their Summary of Product Characteristics (SmPC) recommended daily doses, added on to metformin and SU. Comprehensive comparative analysis involving frequentist meta-analysis and Bayesian NMA compared alogliptin to each DPP-4 inhibitor separately and collectively as a group. Quasi-random effect models were introduced when random effect models could not be estimated. Results The review identified 2186 articles, and 94 full-text articles were assessed for eligibility. Eight RCTs contained appropriate data for inclusion in the NMA. All analyses over all trial population sets produced very similar results, and show that alogliptin 25 mg is as least as effective (as measured by change in HbA1c from baseline, but supported by other outcome measures: change in body weight and FPG from baseline) and safe (as measured by incidence of hypoglycemia and adverse events leading to study discontinuation) as all the other DPP-4 inhibitors in triple therapy. Conclusion This decision-focused systematic review and NMA demonstrated alogliptin 25 mg daily to have similar efficacy and safety compared to other DPP-4 inhibitors, for the treatment of T2DM in adults inadequately controlled on metformin and SU. (Funded by Takeda Development Centre Americas; EXAMINE ClinicalTrials.gov number, NCT00968708). Electronic supplementary material The online version of this article (doi:10.1007/s13300-017-0245-8) contains supplementary material, which is available to authorized users.

Riders to the Sea, Synge’s first play, is an astonishingly mature work of art. Whether we regard it as literature or as drama (a distinction Synge liked to make), it is a masterpiece enjoyed equally in the library or in the theatre; the role of Maurya has a special cachet for actresses like that attached to playing Medea or Lady Macbeth or Hedda Gabler. Like all great works of art it defies definition, seeming inexhaustible in meaning and complexity. The plot is simplicity itself. Maurya, an old woman, hopes that the body of her son, Michael, will be washed ashore. He was drowned nine days earlier. Already Maurya has lost her husband, her father-in-law and four other sons to the sea. When the play opens her two daughters have been given clothes from the body of a drowned man. Before they can discover whether the clothes are Michael’s, Bartley, the youngest son, enters preparing for a journey by sea to the Galway horse-fair. Despite the entreaties of his mother not to go, he sets off. ‘He’s gone now, God spare us,’ his mother cries, ‘and we’ll not see him again.’

Synge’s first full-length play, The Well of the Saints, has been received with more enthusiasm by the critics than by audiences, which have preferred Riders to the Sea and The Playboy. It may be that, like the original Abbey players, they find the vision of the play too narrow and intense and the irony too Swiftian in its misanthropy (softened only in the final act). Willie Fay recorded his impression of the play: I realized that every character in the play from the Saint to Timmy the Smith was bad-tempered right through the play, hence, as I pointed out to Synge, all the bad temper would inevitably infect the audience and make them bad-tempered too. I suggested that the Saint anyway might be made into a good-natured, easy- going man, or that Molly Byrne might be made a lovable young girl, but Synge would not budge. He said he wanted to write ‘like a monochrome painting, all in shades of the one colour’.1

I look on The Aran Islands as my first serious piece of work — it was written before any of my plays. In writing out the talk of the people and their stories in this book, and in a certain number of articles on the Wicklow peasantry which I have not yet collected, I learned to write the dialect and dialogue which I use in my plays.… The Aran Islands throws a good deal of light on my plays. (Prose, p. 47n)

The City of Dublin has long been famous as a centre of culture; this was never more evident than in the second half of the nineteenth century when it was home to such writers of genius as Oscar Wilde, G.B. Shaw, W.B. Yeats, J.M. Synge and James Joyce. Of the five, it is Synge who grounds his dramatic art most exclusively in Ireland, finding in her legends and folk tales, and in her peasantry and their speech, the materials of such masterpieces as Riders to the Sea, The Well of the Saints and The Playboy of the Western World. He was, with Yeats and Lady Gregory, a director of the Abbey Theatre and it was his kind of theatre — rather than Yeats’s — that was to influence the Abbey and shape a new generation of Irish dramatists. His is peasant or folk drama which manages, however, to sound themes that are of universal concern. In all his plays, he champions the imaginative life and condemns whatever seeks to restrain human liberty; he celebrates the richness of the solitary and the dispossessed (tramp and tinker) who are oppressed by society (priest and mob); he dramatizes the plight of men and women whose existence in a menacing and meaningless world he invests with passion and poetry and brutality; he experiments with the form of the drama, wrenching it to new shapes to accommodate his uneasy fusing of the tragic and the comic.

The story of Deirdre, of whom it was prophesied that she would bring destruction on the Sons of Usna, is one of the most beautiful and touching of the Irish legends, and has inspired retelling by such writers as Sir Samuel Ferguson, A. E., Eva Gore-Booth, W. B. Yeats and James Stephens.1 While in Aran, in either 1900 or 1901, Synge made a translation of the Irish text, The Fate of the Children of Uisneach, which had been published in 1898 by the Society for the Preservation of the Irish Language. When, in 1902, he reviewed Lady Gregory’s Cuchulain of Muirthemne, he singled out Deirdre’s lament over the dead Naisi and his brothers as ‘one of the finest passages in the book’. (Prose, p, 369) He wrote to Molly Allgood in 1906, ‘My next play must be quite different from the P. Boy. I want to do something quiet and stately and restrained and I want you to act in it.’2 But The Playboy and illness prevented him turning to the new play; on 22 October 1907, he wrote to Molly: ‘I got a “Deirdre” fit yesterday and I wrote 10 pages of it in great spirits and joy, but alas I know that that is only the go off.

The Shadow of the Glen, like Riders to the Sea, is based on a story Synge heard on the Aran Islands, but the play receives its atmosphere and characters from the hills and glens of County Wicklow, which is south of Dublin and within easy cycling reach of the capital. It was an area well known to Synge since his childhood. In the Autobiography he writes, ‘To wander as I did for years through the dawn of night with every nerve stiff and strained with expectation gives one a singular acquaintance with the essences of the world.’ The ‘essences of the world’, as presented in Synge’s essays on the Wicklow countryside and its people, resemble — though in a muted, more elegiac tone — those presented in Riders to the Sea. Here, too, nature is hostile, and the people are continually haunted by thoughts of death. The Shadow of the Glen lacks the epic quality of Riders to the Sea but, in compensation, Synge adds a psychological dimension lacking in the earlier play. In The Shadow of the Glen we find more human problems plaguing the men and women of the glens — depression, loneliness, madness.

Objective: To evaluate the cost-effectiveness of brentuximab vedotin in patients with R/R sALCL from a UK NHS perspective. Methods: A partitioned survival model used clinical outcomes for brentuximab vedotin from the pivotal phase-2 single-arm trial of brentuximab vedotin in 58 patients with R/R sALCL (SG035-0004; NCT00866047), over a lifetime (30-year) time horizon. Comparison with conventional chemotherapy was based on data from the Canadian British Columbia Cancer Agency registry from 40 patients starting salvage chemotherapy after front-line treatment between 1980 and 2012. Survival was extrapolated using parametric distributions, with brentuximab vedotin risk after the trial period assumed equal to conventional chemotherapy. Other modelling assumptions were based on a systematic literature review and clinical expert opinion. Results: Based on statistical extrapolation, brentuximab vedotin was associated with 3.1 years longer duration in the progression-free survival health state and an overall survival improvement of 5.4 years, prior to discounting. In addition, brentuximab vedotin was associated with 2.5 quality-adjusted life years (QALYs) gained at a total incremental cost of £88 556, resulting in an incremental cost-effectiveness ratio (ICER) of approximately £35 400. Sensitivity analyses of alternative model assumptions provided ICERs ranging from approximately £28 100 to £61 900. Comparing only first-line salvage patients reduced the ICER to £26 800 per QALY gained. Conversely, considering only patients with Eastern Corporative Oncology Group performance status of 0 or 1 increased the ICER to approximately £38 200. At a willingness-to-pay threshold of £50 000, the estimated probability that brentuximab vedotin is cost-effective compared with conventional chemotherapy was 86.5%. Conclusion: Compared to conventional chemotherapy, and considering the full survival period, brentuximab vedotin may provide a valuable treatment choice for patients with R/R sALCL, a population with limited therapeutic options.