University of Groningen
Economic aspects of public health programmes for infectious disease control
Ong, Koh Jun
DOI:
10.33612/diss.98545253
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2019
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Ong, K. J. (2019). Economic aspects of public health programmes for infectious disease control: studies on human immunodeficiency virus & human papillomavirus. University of Groningen.
https://doi.org/10.33612/diss.98545253
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
Summary
Samenvatting
Acknowledgements
Research Institute SHARE
&
SUMMARY
SUMMARY
Despite existing public health control programmes for HIV and HPV prevention, further opportunities exist that may reduce the incidence of infection and related disease outcomes. These may be in the form of primary prevention i.e. preventing new infection establishment prior to exposure, or secondary prevention where infected persons are diagnosed and treated. This thesis explored the use of different economic analytical methods to address some of the key policy questions around commissioning of public health HIV and HPV control programmes in England.
For HIV, despite existing prevention efforts, which include promotion of condom use, needle exchange programmes and immediate antiretroviral use in diagnosed positive persons to reduce onward transmission, HIV incidence had remained relatively stable over 2006 to 2015. As evidence began to emerge on the efficacy of HIV antiretrovirals use in uninfected persons prior to sexual exposure in preventing infection (called pre-exposure prophylaxis, or PrEP for short), the subsequent policy question for national commissioners was whether a public health prevention programme delivering PrEP would provide value for money and be affordable. Chapter 2 of this thesis describes a cost-effectiveness and budget impact analysis that I conducted to inform this. It was found that such a programme could be cost-effective but this conclusion was highly uncertain, given its value for money is dependent on the risk of HIV infection in those given PrEP. Moreover, the high cost of the intervention at list price, and the size of the population needed to be given PrEP to achieve substantial public health benefits meant that a public health programme could pose an affordability challenge to the national health care system. This resulted in a further large scale, pragmatic public health PrEP trial in England to ascertain the value for money of such a programme.
The next chapter, Chapter 3, in this thesis concerns the issue with patents and market exclusivity of HIV antiretrovirals, where the impact of generic antiretroviral availability on lifetime HIV care cost estimates was considered. It was found that, using current list price, the average total HIV care cost for a person living in England was close to £200,000. This could be around £70,000 if we factor in generic antiretroviral availability at 10% of current list price from the point where they lose market exclusivity. In the context of this specific disease area, where generic antiretrovirals are already widely used in developing countries and generics are likely to be available where market size and usage is sufficiently large, where most currently prescribed antiretrovirals will lose market exclusivity within the next decade, and where treatment is currently lifelong, incorporation of generic prices as they become available in lifetime cost estimation should be the approach to technology appraisals in this area. This means that for future economic evaluation of new HIV interventions, the comparator i.e. current care should incorporate such cost adjustments in anticipation of generic availability.
In addition to primary HIV prevention using PrEP, secondary prevention initiatives such as population HIV screening in areas with high prevalence could reduce the number
158
&
ADDENDUM
of undiagnosed HIV infections with corresponding reduction in onward HIV transmission. Chapter 4 considers the budget impact of HIV screening. In a commissioning landscape where local commissioners are responsible for their local population’s public health, a cost-consequences analysis was conducted to illustrate the cost of screening per unit of a reactive HIV test result, for HIV screening offered either in general practice or as part of routine blood testing during acute hospital general medical admissions. Although HIV screening costs less in the latter setting, staff cost and characteristics of the population of attendees (HIV prevalence) affect cost per reactive test identified, with most value obtained where staff cost is low and where local population prevalence is high.
Chapters 5 and 6 present work on HPV prevention. The English national HPV vaccination programme has been in place since 2008, offering HPV vaccination to girls in year 8 of school and with high vaccination coverage, boys have benefited indirectly through herd immunity. However, particular populations may not be so well protected and they include men who have sex with men (MSM), where sexual exposure occurs largely within an unvaccinated population. Thus, the previously constructed heterosexual dynamic HPV infection model was adapted to consider MSM HPV transmission to assess the cost-effectiveness of MSM HPV vaccination delivery via genitourinary medicine clinics in England (Chapter 5). It found such programme to be cost-effective with vaccination provision for all MSM up to age of 40 years, regardless of HIV status. This informed the recommendation for a national MSM HPV vaccination programme in England. A subsequent systematic review in Chapter 6 found different MSM HPV vaccination strategies to be cost-effective, with some focusing on HIV-positive MSM whilst others considering those with high grade anal intra-epithelial neoplasia. Despite different modelling approach, with most papers presenting results from static models, cost-effectiveness results were sensitive to assumed vaccination efficacy and price.
As assessment of HPV vaccination increasingly expand to consider impact on non-cervical outcomes, it became relevant to consider whether existing assumptions around their related cost and utility were appropriate. Chapter 7 presents a systematic review and meta-analysis I conducted. Although the papers identified were limited to healthcare provision from countries with “Beveridge” style healthcare system, substantial differences in cost and utility estimates remained. Such differences could be attributed to different stages of disease diagnoses and management, as well as the variety in specific cancer sites considered, especially for head and neck cancers. Future application of such estimates must consider suitability to the model, whether they are aligned in terms of the patient population and disease management pathway.
In summary, this thesis explored different national public health control programmes, such as HIV PrEP, MSM HPV vaccination, and HIV screening using various approaches to advise policy makers on their value for money. Key learning outcomes, discussed in Chapter 8, include the emphasis that cost-effectiveness should not be considered independently of budget impact and affordability considerations and that health economists providing such economic analyses need to be mindful of the evolving and dynamic disease management
&
SUMMARY
landscape, including market dynamics, which affects cost of treatment. It also showed the value of using systematic reviews in comparing findings from cost-effectiveness analyses, and highlighted the need for careful consideration of background economic assumptions used in models.
160
&
ADDENDUM
SAMENVATTING
Ondanks bestaande volksgezondheidscontroleprogramma’s voor de preventie van HIV en HPV, bestaan er nog meer mogelijkheden die de incidentie van infecties en gerelateerde ziektebelasting kunnen verminderen. Deze kunnen de vorm hebben van primaire preventie, d.w.z. het voorkomen van nieuwe infectie-inrichting voorafgaand aan blootstelling, of secundaire preventie waarbij geïnfecteerde personen worden gediagnosticeerd en behandeld. In dit proefschrift werd het gebruik van verschillende economische analysemethoden onderzocht om enkele van de belangrijkste beleidsvragen rond de inbedrijfstelling van HIV- en HPV-bestrijdingsprogramma’s voor de volksgezondheid in Engeland aan te pakken.
Voor HIV, ondanks bestaande preventie-inspanningen, waaronder bevordering van condoomgebruik, naalduitwisselingsprogramma’s en onmiddellijk antiretroviraal gebruik bij gediagnosticeerde positieve personen om verdere overdracht te verminderen, was de incidentie van HIV relatief stabiel in de periode 2006-2015. Toen bewijs begon te ontstaan over de werkzaamheid van het gebruik van HIV-antiretrovirale middelen bij niet-geïnfecteerde personen voorafgaand aan seksuele blootstelling bij het voorkomen van infectie (profylaxe vóór blootstelling genoemd, of kortweg PrEP), de volgende beleidsvraag voor nationale commissarissen was of een preventieprogramma voor de volksgezondheid dat PrEP oplevert, betaalbaar. Hoofdstuk 2 van dit proefschrift beschrijft een kosteneffectiviteits- en budgetimpactanalyse die ik heb uitgevoerd om dit te informeren. Er werd vastgesteld dat een dergelijk programma kosteneffectief zou kunnen zijn, maar deze conclusie was zeer onzeker, aangezien de prijs-kwaliteitverhouding ervan afhankelijk is van het risico op HIV-infectie bij degenen die PrEP krijgen. Bovendien moesten de hoge kosten van de interventie tegen de lijstprijs en de omvang van de bevolking PrEP krijgen om substantiële voordelen voor de volksgezondheid te realiseren, waardoor een volksgezondheidsprogramma een uitdaging voor de betaalbaarheid van het nationale gezondheidszorgsysteem kon vormen. Dit resulteerde in een verder grootschalig, pragmatisch PrEP-onderzoek voor de volksgezondheid in Engeland om de prijs-kwaliteitverhouding van een dergelijk programma vast te stellen.
Het volgende hoofdstuk, hoofdstuk 3, in dit proefschrift gaat over het probleem met patenten en marktexclusiviteit van HIV-antiretrovirale middelen, waarbij het effect van generieke antiretrovirale beschikbaarheid op de geschatte kosten van levenslange HIV-zorg werd overwogen. Het bleek dat, met behulp van de huidige lijstprijs, de gemiddelde totale HIV-zorgkosten voor een persoon die in Engeland woonde bijna £ 200.000 waren. Dit zou ongeveer £ 70.000 kunnen zijn als we rekening houden met de beschikbaarheid van generieke antiretrovirale middelen tegen 10% van de huidige lijstprijs vanaf het moment dat ze marktexclusiviteit verliezen. In de context van dit specifieke ziektegebied, waar generieke antiretrovirale middelen al op grote schaal worden gebruikt in ontwikkelingslanden en generieke geneesmiddelen waarschijnlijk beschikbaar zullen zijn waar de marktomvang en het gebruik voldoende groot is, waar de meeste momenteel voorgeschreven antiretrovirale
&
SAMENVATTING
middelen de marktexclusiviteit binnen het volgende decennium zullen verliezen, en waar de behandeling momenteel levenslang is, moet de opname van technologische beoordelingen op dit gebied de opname van generieke prijzen zodra deze beschikbaar komen bij de schatting van de levensduurkosten. Dit betekent dat voor toekomstige economische evaluatie van nieuwe HIV-interventies, de comparator, d.w.z. de huidige zorg, dergelijke kostenaanpassingen moet omvatten in afwachting van generieke beschikbaarheid.
Naast primaire HIV-preventie met behulp van PrEP, zouden secundaire preventie-initiatieven zoals bevolkingsonderzoek naar HIV in gebieden met een hoge prevalentie het aantal niet-gediagnosticeerde HIV-infecties kunnen verminderen met een overeenkomstige vermindering van verdere HIV-overdracht. Hoofdstuk 4 gaat in op de budgettaire impact van HIV-screening. In een landschap van opdrachtgevers waar lokale commissarissen verantwoordelijk zijn voor de volksgezondheid van hun lokale bevolking, is een kosten-consequentieanalyse uitgevoerd om de kosten van screening per eenheid van een reactief HIV-testresultaat te illustreren, voor HIV-screening aangeboden in de huisartspraktijk of als onderdeel van routinematige bloedtesten tijdens acute medische ziekenhuisopnames. Hoewel HIV-screening minder kost in de laatste setting, hebben personeelskosten en kenmerken van de populatie van aanwezigen (HIV-prevalentie) invloed op de kosten per geïdentificeerde reactieve test, waarbij de meeste waarde wordt verkregen waar personeelskosten laag zijn en waar de lokale bevolking hoog is.
Hoofdstukken 5 en 6 presenteren werk over preventie. Het Engelse nationale HPV-vaccinatieprogramma bestaat sinds 2008 en biedt meisjes HPV-vaccinatie in het jaar 8 van school. Jongens met een hoge vaccinatiegraad hebben indirect baat bij kudde-immuniteit. Bepaalde populaties zijn echter mogelijk niet zo goed beschermd en omvatten mannen die seks hebben met mannen (MSM), waar seksuele blootstelling grotendeels voorkomt in een niet-gevaccineerde populatie. Het eerder geconstrueerde heteroseksuele dynamische HPV-infectiemodel werd dus aangepast om MSM HPV-transmissie te overwegen om de kosteneffectiviteit van MSM HPV-vaccinatie via urogenitale geneeskunde in Engeland te beoordelen (hoofdstuk 5). Het vond een dergelijk programma kosteneffectief met vaccinatievoorziening voor alle MSM tot de leeftijd van 40 jaar, ongeacht de HIV-status. Dit vormde de aanbeveling voor een nationaal MSM HPV-vaccinatieprogramma in Engeland. Een daaropvolgende systematische review in hoofdstuk 6 wees uit dat verschillende MSM HPV-vaccinatiestrategieën kosteneffectief zijn, waarbij sommige zich richten op HIV-positieve MSM, terwijl anderen die met hoogwaardige anale intra-epitheliale neoplasie overwegen. Ondanks de verschillende modelleringsbenadering, waarbij de meeste artikelen resultaten van statische modellen presenteren, waren de kosteneffectiviteitsresultaten gevoelig voor de veronderstelde werkzaamheid en prijs van vaccinatie.
Naarmate de beoordeling van HPV-vaccinatie in toenemende mate uitbreidde om de impact op niet-cervicale resultaten te overwegen, werd het relevant om te overwegen of bestaande veronderstellingen over hun gerelateerde kosten en bruikbaarheid passend waren. Hoofdstuk 7 presenteert een systematische review en meta-analyse die ik heb uitgevoerd.
162
&
ADDENDUM
Hoewel de geïdentificeerde documenten beperkt waren tot zorgverlening uit landen met een gezondheidszorgsysteem in de stijl van “Beveridge”, bleven er aanzienlijke verschillen in kosten en nutsschattingen. Dergelijke verschillen kunnen worden toegeschreven aan verschillende stadia van ziektediagnoses en -beheer, evenals de variëteit in specifieke kankersites die worden overwogen, vooral voor hoofd- en nekkanker. Toekomstige toepassing van dergelijke schattingen moet de geschiktheid voor het model in overweging nemen, of ze zijn afgestemd op de patiëntenpopulatie en het ziektebeheerspad.
Samenvattend onderzocht dit proefschrift verschillende nationale volksgezondheidscontroleprogramma’s, zoals HIV PrEP, MSM HPV-vaccinatie en HIV-screening met behulp van verschillende benaderingen om beleidsmakers te adviseren over hun waar voor hun geld. Belangrijke leerresultaten, besproken in hoofdstuk 8, omvatten de nadruk dat kosteneffectiviteit niet onafhankelijk van budgettaire impact en betaalbaarheidsoverwegingen moet worden beschouwd en dat gezondheidseconomen die dergelijke economische analyses leveren, rekening moeten houden met het zich ontwikkelende en dynamische landschap voor ziektebeheersing, met inbegrip van de markt. dynamiek, die de behandelingskosten beïnvloedt. Het toonde ook de waarde aan van het gebruik van systematische beoordelingen bij het vergelijken van bevindingen uit kosten-batenanalyses, en benadrukte de noodzaak van zorgvuldige afweging van economische achtergrondveronderstellingen die in modellen worden gebruikt.
&
ACKNOWLEDGEMENTS
ACKNOWLEDGEMENTS
I am most grateful to God for giving me the opportunity to work on this thesis with some of the most brilliant and outstanding experts in the fields of health economics, public health, epidemiology, statistics, and infectious diseases modelling. This thesis would not have been completed without their guidance, help, and encouragement. Most notably, thank you to my PhD supervisors (Professor Maarten J Postma and Professor Mark Jit ) and co-supervisors (Dr Albert Jan van Hoek and Dr Kate Soldan) for their continued patience, dependable presence and constructive feedback, over the seven years from 2013 to 2019, ensuring that this thesis comes to fruition.
When it was first suggested that I pursue a PhD by publication back in 2013, I had limited experience with peer-reviewed publications and at the outset, had not appreciated their importance. However, in hindsight, this has been among the most valuable learning outcomes from this process, not only because it ensures the work conducted is robust, but it also allows the scientific research material to become more widely available, potentially contributing to further development in the field.
In the next few paragraphs, I wish to thank specific individuals who have been vital to the work presented in this thesis.
Albert Jan (AJ) was my pillar of support over all these years, from when I first joined Public Health England as a fresh health economist. He taught me how to address health economics questions in the most intriguing and enjoyable ways, bringing the research to life. It has been such a blessing working with him, and none of this would have been possible without his contribution. Thank you AJ for your friendship, the many intellectual discussions we had, and for helping me throughout this journey.
I got to know Maarten through AJ, who has provided continued guidance and was ever-present throughout the thesis. I have always appreciated his relaxed but vital approach to managing work, which has made this whole process easy and smooth. And thanks Maarten for checking the Dutch translations whilst on holiday!
I still remember the first time I met Mark and Kate in December of 2012. Firstly, thank you for the opportunity to work at Public Health England and for nurturing me as I began my journey as a health economist all those years ago. Mark has provided substantial leadership on health economics, modelling, statistics, JCVI, and a range of other topics, which significantly developed my knowledge and skills in this area. Kate has also been instrumental in my professional development, always being there whenever I needed extra direction. It has been a great joy working with both of you.
164
&
ADDENDUM
I would also like to especially mention Professor Noel Gill, who although is neither my PhD supervisor nor promoter, has contributed substantially to the work in this thesis. Thank you for teaching me so much about public health and epidemiology; it has been a much-privileged learning experience as we address the challenges of public health policy, strategy, and implementations. In particular, thank you for the inspiration to constantly prioritise public health improvements through translation and application of academic discussions into real-world policies that improve the health of the public.
The lengthy publication process required substantial input from all co-authors, and I would like to thank all of them for their time and brilliant work, be it intellectual input in structuring and guiding the evaluations, answering my many questions around epidemiology, statistics, infectious diseases modelling, clinical disease management, help with systematic reviews, understanding available national surveillance data, or help with meeting journal’s digital output requirements. Their names are listed in alphabetical order as follows, Dr Adrian Palfreeman, Dr Alicia C Thornton, Dr Alison Brown, Allen Lin, Dr Anthony Nardone, Charlotte Pavitt, Cuong Chau, Dr David Mesher, Debbie Mou, Dr John Saunders, Dr Jose Figuera, Dr Laura Waters, Lorna Burns, Marta Checchi, Dr Monica Desai, Natasha Ratna, Professor Noel Gill, Peter Kirwan, Dr Ross Harris, Dr Sarah Woodhall, Sarika Desai, Thomas Hartney, Paula Blomquist, Dr Valerie Delpech, and Dr Yoon Choi. Also, special thanks to the peer reviewers and journal editors for their time and constructive feedback to improve the quality of the write-up.
In addition to those mentioned, sincere thanks to the many outstanding colleagues within the HIV and STI surveillance department, the Statistics, Modelling and Economics Unit and others at Public Health England Colindale site where I was based. Thank you to (in alphabetical order; and apologies if I have inadvertently missed anyone out) Alej, Alicia, André, Aimi, Anna, Archana, Arlene, Dana, Dolores, Doris, Emilia, Emma, Erna, Erol, Frank, Hamish, Holly, Irenjeet, John, Joyce, Julie, Kate, Katy, Kevin, Koen, Linda, Manisha, Martina, Nalini, Nastassya, Nick, Norman, Parnam, Patricia, Paul, Peter, Rajani, Ruth, Sara, Sarah, Sheeja, Steph, Stuart, Terry, Timo, and Zheng, most importantly for your friendship, as well as time and guidance in epidemiology, statistics, national surveillance system, and public health. I had a very good time at Colindale.
Furthermore, thank you to my NHS England colleagues for the encouragement and support they have very kindly provided to help me complete this work.
The final steps to Hora Finita include assessment of the thesis, publication of the book, and the public defence ceremony. Thank you to all involved, including examiners and opponents, AJ, Kate, Maarten, Mark and Stuart for proofreading, Truus for administrative support, Michael and Aleksandra for help with finalising the printing, as well as my family
&
ACKNOWLEDGEMENTS
and supporting friends and all who are present on the thesis public defence day, and all who sent their well-wishes although could not be present in person.
Last but not least, thank you to my dear family, in particular, my father, my mother, my husband, my children, and my siblings, for their continued encouragement, support and love.
166
&
ADDENDUM
RESEARCH INSTITUTE SHARE
This thesis is published within the Research Institute SHARE (Science in Healthy Ageing and healthcaRE) of the University Medical Center Groningen / University of Groningen.
Further information regarding the institute and its research can be obtained from our internet site: http://www.share.umcg.nl/
More recent theses can be found in the list below. ((co-) supervisors are between brackets)
2019
Dierselhuis EF
Advances of treatment in atypical cartilaginous tumours (prof SK Bulstra, prof AJH Suurmeijer, dr PC Jutte, dr M Stevens)
Gils A van
Developing e-health applications to promote a patient-centered approach to medically unexplained symptoms
(prof JGM Rosmalen, prof RA Schoevers)
Notenbomer A
Frequent sickness absence; a signal to take action (prof U Bultmann, prof W van Rhenen, dr CAM Roelen)
Bishanga DR
Improving access to quality maternal and newborn care in low-resource settings: the case of Tanzania
(prof J Stekelenburg, dr YM Kim)
Tura AK
Safe motherhood: severe maternal morbidity and mortality in Eastern Ethiopia (prof SA Scherjon, prof J Stekelenburg, dr TH van den Akker)
Vermeiden CJ
Safe motherhood : maternity waiting homes in Ethiopia to improve women’s access to maternity care
&
RESEARCH INSTITUTE SHARE
Schrier E
Psychological aspects in rehabilitation (prof PU Dijkstra, prof JHB Geertzen)
Malinakova K
Spirituality and health: their associations and measurement problems (prof SA Reijneveld, prof P Tavel, dr JP van Dijk)
Dijkhuizen A
Physical fitness and performance of daily activities in persons with intellectual disabilities and visual impairment; towards improving conditions for participation
(prof CP van der Schans, dr A Waninge, dr WP Krijnen)
Graaf MW de
The measurement and prediction of physical functioning after trauma (prof E Heineman, dr IHF Reininga, dr KW Wendt)
Vrijen C
Happy faces and other rewards; different perspectives on a bias away from positive and toward negative information as an underlying mechanism of depression
(prof AJ Oldehinkel, prof CA Hartman, prof P de Jonge)
Moye Holz DD
Access to innovative medicines in a middle-income country; the case of Mexico and cancer medicines
(prof HV Hogerzeil, prof SA Reijneveld, dr JP van Dijk)
Woldendorp KH
Musculoskeletal pain & dysfunction in musicians (prof MF Reneman, prof JH Arendzen, dr AM Boonstra)
Mooyaart JE
Linkages between family background, family formation and disadvantage in young adulthood
(prof AC Liefbroer, prof F Billari)
Maciel Rabello L
The influence of load on tendons and tendinopathy; studying Achilles and patellar tendons using UTC
168
&
ADDENDUM
Holvast F
Depression in older age
(prof PFM Verhaak, prof FG Schellevis, prof RC Oude Voshaar, dr H Burger) For earlier theses visit our website
