Transcript Ageing and treatment gaps 2013 09 13

Are low treatment uptake rates due to polymorbidity
and polymedication issues? Perspectives from the
osteoporosis treatment gap in England and in France.
SMi Geriatric Safe Medicines Summit 16.9.13
Jonathan Guillemot, PhD candidate, Institute of Gerontology, King’s College
London
[email protected]
Personal statement
1.
I am a part-time analyst at Amaris (consultancy) at the
department of Health Economics and Outcomes Research
(HEOR).
2. I am a PhD candidate at King’s College London, Institute of
Gerontology.
3. The title of the research: ‘Drug selection processes for
older people: case study of osteoporosis in England and
France.’
4. Amaris is a sponsor to this research.
Outline of presentation
1.
2.
3.
4.
5.
6.
7.
Perspective on public health and context
Epidemiology and burden of osteoporosis
Existing management options
Past and current clinical recommendations
Past and current treatment consumption trends
Explanations for the treatment gap
Limitations and conclusion
1. Perspective on public health and context
• Issues of public health
– How can one define the right amount of healthcare to
provide?
– Does this question (and its answer) differ between age
groups and among older people?
– Do older people suffer from a treatment gap? If yes, what
are the causes?
• The decision to treat and the drug selection process
– is a complex process, especially in the context of geriatric
medicine
– involves many different institutions and actors
1. Perspective on public health and context
• What is a treatment gap?
– Situation where treatment provision systematically fails to
satisfy treatment needs
• One specificity of the health care market: limitlessness
of demand
– Situation where treatment uptake rates are
systematically lower than recommended practice
1. Perspective on public health and context
• Aims
– Identify the presence of a treatment gap in a specific
disease area in older people
– Identify causes of treatment gaps in older people
• Women more often referred to
• Study case of osteoporosis
• Comparative approach between England and France
– Preliminary study: no comparable results
– Data often reporting the UK rather than England
2. Epidemiology and burden of osteoporosis
• What is osteoporosis?
– ‘Disease characterised by low bone mass and microarchitectural deterioration of bone tissue leading to
enhanced bone fragility and a consequent increase in
fracture incidence.’ [1,2]
– It can be related to ageing (i.e. postmenopausal
osteoporosis in women) or treatments-induced
• This study focuses on age-induced osteoporosis in
both men and women
[1] Consensus development conference. 1993. “Diagnosis, prophylaxis, and treatment of osteoporosis.” The
American journal of medicine 94(6): 646–50.
[2] Melton, L J, and B L Riggs. 1983. “Epidemiology of age-related fractures.” In The Osteoporotic Syndrome,
ed. L V Avioli. New York: Grune and Stratton, p. 45–72.
2. Epidemiology and burden of osteoporosis
• Is osteoporosis an appropriate case?
– Disease prevalent in older people?
– Well-known disease?
– Existence of collected data?
– Existence of long-term treatment options?
• Why compare England and France?
– Two rather similar socio-economic contexts
– Two State-centred health systems using different
approaches
– Quite different outcomes
2. Epidemiology and burden of osteoporosis
• Epidemiology
– 10-year probability of major fracture in 65+ women with a
prior fragility fracture [1]
• Broad variability: >25% in Denmark; <3% in Tunisia
• United Kingdom: ~20%; France: ~12%
[2]
[1] Kanis, J. a, Odén, a, McCloskey, E. V, Johansson, H., Wahl, D. a, & Cooper, C. (2012). A systematic
review of hip fracture incidence and probability of fracture worldwide. Osteoporosis international : a
journal established as result of cooperation between the European Foundation for Osteoporosis and the
National Osteoporosis Foundation of the USA, 23(9), 2239–56. doi:10.1007/s00198-012-1964-3
[2] http://www.iofbonehealth.org/what-is-osteoporosis, 26.08.2013
2. Epidemiology and burden of osteoporosis
• Burden of disease
– Impact on daily life of fragility fracture [1]
• Pain, loss of physical functioning, social and mental consequences,
premature death (QALYs* lost due to fracture)
– First year costs of a hip fracture (€, 2010) [1]
• UK: € 11,055-20,359 (~£9,000-£17,000)**
• France: € 12,030-19,004 (~£10,000-£16,000)**
– In 45+ women, osteoporosis results in more hospital days
than diabetes, myocardial infarction and breast cancer [2]
[1] Ström, O. et al. 2011. “Osteoporosis: burden, health care provision and opportunities in the EU […].”
Archives of osteoporosis 6(1-2): 59–155.
[2] Kanis JA, Delmas P, Burckhardt P, et al. (1997) Guidelines for diagnosis and management of osteoporosis.
The European Foundation for Osteoporosis and Bone Disease. Osteoporos Int 7:390.
*Quality-Adjusted Life-Year. **Approximates
3.1 Existing management options
• Management responses do exist
– Exercise, nutrition, behavioural changes (risk factor
reduction), pharmacological responses
• Pharmacological responses
– Bisphosphonates
– Hormone replacement therapy
– Other pharmacological options
3.1 Existing management options
Bisphosphonates
Anti-osteoporotic
medications
SERM*
RANK ligand inhibitors
Parathyroid hormones
Dual action bone agent
*SERM: Selective Oestrogen Receptor Modulator
Alendronate
Ibandronate
Etidronate
Zoledronate
Raloxifene
Bazedoxifene
Denosumab
Teriparatide
PTH(1-84)
Strontium Ranelate
3.2 Efficacy profiles
Management option [ref]
Reduction in incidence of
fractures in osteoporotic
women
Alendronate [1]
Risedronate [2-3]
45%
20%-50%
Zoledronate [4]
Ibandronate [5-6]
Denosumab [7]
25%-70%
30%-40%
20%-70%
Strontium Ranelate [8]
15%-40%*
*Safety profile has since been questioned [9]
3.2 Efficacy - references
[1] Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE 2005 Meta-analysis of the efficacy of alendronate for the
prevention of hip fractures in postmenopausal women. Osteoporos Int 16:468-474
[2] Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW,
Miller PD 1999 Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a
randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344-1352
[3] Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R 2000 Randomized
trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with
Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83-91
[4] Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H,
Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR 2007 Once-yearly zoledronic acid for
treatment of postmenopausal osteoporosis. N Engl J Med 356:1809-1822
[5] Delmas PD, Recker RR, Chesnut CH 3rd, Skag A, Stakkestad JA, Emkey R, Gilbride J, Schimmer RC, Christiansen C 2004 Daily and
intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE
study. Osteoporos Int 15:792-798
[6] Chesnut III CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD
2004 Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res
19:1241-1249
[7] Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S,
Zanchetta J, Libanati C, Siddhanti S, Christiansen C 2009 Denosumab for prevention of fractures in postmenopausal women with
osteoporosis. N Engl J Med 361:756-765
[8] Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Curiel MD, Sawicki A, Goemaere S,
Sorensen OH, Felsenberg D, Meunier PJ 2005 Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women
with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90:2816-2822
[9] MHRA. Strontium ranelate (Protelos): risk of serious cardiac disorders—restricted indications, new contraindications, and warnings.
April 2013. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON266148. Visited 27.08.2013
4. Past and current clinical recommendations
• Recommendations
– Document from an official institution (or authoritative)
detailing the conditions for prescription of a drug
– France: Haute Autorité de Santé (HAS), Groupe de
Recherche et d’Information sur les Ostéoporoses (GRIO)
– England: National Institute for Health and Care Excellence
(NICE), National Osteoporosis Guideline Group (NOGG)
• Basis of recommendations
– Clinical efficacy, including safety profiles
– Cost-effectiveness (in a broad term)/price
– Differences between England and France
4. Past and current clinical recommendations
• English recommendations
– Royal College of Physicians (RCP) (1999,2000)
– NICE TA* 87 (2005)
– NICE TA 160, TA 161 (2008, 2010, 2011)
– NOGG (2008, 2010, 2013)
• Fairly consistent recommendations over time
– Treatment recommended in women, with a previous
fragility fracture or with a low Bone Mass Density (BMD) (Tscore< -2.5SD)
– First line: bisphosphonates mainly
*TA: Technology Assessment
4. Past and current clinical recommendations
• French recommendations
– AFSSAPS (2003, 2006)
– HAS (2006)
– GRIO (2012)
• No main differences with English recommendations
– Treatment recommended in women, with a previous
fragility fracture or with a low Bone Mass density) BMD (Tscore< -2.5SD)
– First line: bisphosphonates mainly
5.1 Past and current treatment consumption trends
• Anti-osteoporotic drug consumption in France (in DDDs* per
100,000 population) [1]
400000
350000
Alendronate
300000
Risedronate
Etidronate
250000
Ibandronate
200000
Zoledronic acid
150000
Raloxifene
100000
Strontium Ranelate
Teriparatide
50000
PTH
0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
[1] Ström, O. et al. 2011.
*Defined Daily Dosage
5.1 Past and current treatment consumption trends
• Anti-osteoporotic drug consumption in England (in DDDs* per
100,000 population[1]
400000
350000
Alendronate
300000
Risedronate
Etidronate
250000
Ibandronate
200000
Zoledronic acid
150000
Raloxifene
100000
Strontium Ranelate
Teriparatide
PTH
50000
0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
[1] Ström, O. et al. 2011.
*Defined Daily Dosage
5.1 Past and current treatment consumption trends
• Combined drug consumption in France and England (in DDDs* per
100,000 population) [1]
800000
700000
600000
500000
400000
Total FR
300000
Total UK
200000
100000
0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
[1] Ström, O. et al. 2011.
*Defined Daily Dosage
5.1 Past and current treatment consumption trends
• Very strong increase in anti-osteoporotic drug use in both countries
– Bisphosphonates largely dominant in both countries, especially
alendronate
• Diverse patterns of drug consumption
– Consumption more diverse in France
– Alendronate more predominant in England
• Recent data suggests that the trend reversed after 2010 [1, data not
yet available]
– Supported by recent clinical doubts regarding the extent of
adverse events?
[1] Hernlund, E., Svedbom, A., Ivergard, M., & Compston, J. (2013). Osteoporosis in the European Union:
Medical Management, Epidemiology and Economic Burden Arch Osteoporos 2013 (key findings). Archives of
Osteoporosis. IOF website. Retrieved from http://www.iofbonehealth.org/osteoporosis-european-unionmedical-management-epidemiology-and-economic-burden
5.2 Optimal consumption levels
• What is the right/optimal consumption level?
• Difficulty to estimate
– Osteoporosis management suffers from compliance problems
• Meaning of “Exceeding the fracture risk threshold”
– FRAX tool: risk assessment tool to define treatment
requirements [1]
[1] Kanis, J. a, Johnell, O., Oden, a, Johansson, H., & McCloskey, E. (2008). FRAX and the assessment of fracture
probability in men and women from the UK. Osteoporosis international, 19(4), 385–97. doi:10.1007/s00198-007-0543-5
5.3 Treatment gap
• Number of men and women (in thousands) above 50 years
exceeding the fracture risk threshold for treatment and the
potential number treated [1]
France
Treated
Untreated
UK
0
1000000
2000000
3000000
• Findings supported by a 2006 systematic literature review [2]
[1] Ström, O. et al. 2011. “Osteoporosis: burden, health care provision and opportunities in the EU: a report
prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of
Pharmaceutical Industry Associations (EFPIA).” Archives of osteoporosis 6(1-2): 59–155.
[2] Giangregorio, L., Papaioannou, a, Cranney, a, Zytaruk, N., & Adachi, J. D. (2006). Fragility fractures and the
osteoporosis care gap: an international phenomenon. Seminars in arthritis and rheumatism, 35(5), 293–305.
doi:10.1016/j.semarthrit.2005.11.001
5.3 Treatment gap
• A treatment gap increasing with age and gender-sensitive
– Diagnosis was more likely in older patients [1]
– Treatment was more likely in younger patients [1]
– After fragility fracture, women were more likely to receive
diagnosis and prescription than men [1]
– Varied according to living arrangements [1]
[1] Giangregorio, L., Papaioannou, a, Cranney, a, Zytaruk, N., & Adachi, J. D. (2006). Fragility fractures and the
osteoporosis care gap: an international phenomenon. Seminars in arthritis and rheumatism, 35(5), 293–305.
doi:10.1016/j.semarthrit.2005.11.001
6. Explanations for the treatment gap
Polymorbidity/polymedication
Specificities of osteoporosis
Healthcare resources allocation
Attempts to mitigate the gap
6.1 Polymorbidity and polymedication [1]
• Many older people suffer from several conditions and are
polymedicated [2]
• Recommendations usually cover one single condition [1]
• Polymedication induces potential interactions and a iatrogenic
risk
• Is osteoporosis a secondary/less urgent disease?
– Alternative approaches: exercise, fall prevention schemes…
[1] Vogt-Ferrier, N. (2011). Older patients, multiple comorbidities, polymedication… should we treat everything?
European Geriatric Medicine, 2(1), 48–51. doi:10.1016/j.eurger.2010.11.011
[2] Auvray, L., & Sermet, C. (2002). Consommations et prescriptions pharmaceutiques chez les personnes
âgées. Gérontologie et société, 103(4), 13. doi:10.3917/gs.103.0013
6.1 Polymorbidity and polymedication
• Average number of drugs per day in older people (not for
French/English comparison)
5
4
3
France [1]
England [2]
2
1
0
65-74
75-84*
85+*
[1] Auvray, L., & Sermet, C. (2002). Consommations et prescriptions pharmaceutiques chez les personnes âgées.
Gérontologie et société, 103(4), 13. doi:10.3917/gs.103.0013
[2] Chen, Y. F., Dewey, M. E., & Avery, a J. (2001). Self-reported medication use for older people in England and
Wales. Journal of clinical pharmacy and therapeutics, 26(2), 129–40. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/11350536
* Statistics for England included two age groups, i.e. 65-74 and 75+
6.2 Specificities associated with osteoporosis
• Invisible disease, until fractures occur
• Lack of awareness (though much improved) of healthcare
practices in hospital following fractures [1]
• Issue of compliance: treatments may be complex
• To what extent is the treatment gap the result of a decision not
to treat?
[1] Haaland, D. a, Cohen, D. R., Kennedy, C. C., Khalidi, N. a, Adachi, J. D., & Papaioannou, A. (2009). Closing the
osteoporosis care gap: increased osteoporosis awareness among geriatrics and rehabilitation teams. BMC
geriatrics, 9, 28. doi:10.1186/1471-2318-9-28
6.3 Limited healthcare resources
• Limited healthcare resources
– Prioritising the young/intergenerational equity: the fair innings
argument [1]
– Health care rationing: can health care system fund all costeffective interventions?
– Ageism?
[1] Williams, A. (1997). Intergenerational equity: an exploration of the “fair innings” argument. Health
economics, 6(2), 117–32. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9158965
6.4 Attempts to mitigate under-treatment rates
• The Quality and Outcomes Framework (QOF): an attempt to
mitigate the treatment gap
– Incentive tool for GPs in England
– Points associated with achievements
– Osteoporosis: a goal since the 2012-2013 QOF [1]
• Encourages the diagnosis and treatment of osteoporosis
• Recognises the existence of a gap
[1] BMA, & NHS Employers. (2012). Quality and Outcomes Framework for 2012/13. Retrieved from
http://bma.org.uk/practical-support-at-work/contracts/independent-contractors/qof-guidance/qof-guidanceprevious-revisions
7. Limitations and conclusion
• Osteoporosis was used in this presentation as a case study to
assess the existence of treatment gaps in older people
– A clinical need exists in older people
– There are recommended, cheap and cost-effective
treatments on the market
– Despite a significant increase in drug use in the past 10 years,
treatment uptake rates are low and older populations seem to
be subject to under-treatment
7. Limitations and conclusion
• How does one define the optimal treatment uptake rate?
• How does one measure treatment uptake rates?
• Are decisions not-to-treat systematically ‘feeding the gap’?
– Polymorbidity and polymedication
• Possible reasons for these low treatment uptake rates
– Specificities associated with osteoporosis?
– Limited healthcare resources
7. Limitations and conclusion
• Other related research questions
– Inclusion of older people in clinical trials
– Effectiveness of measurement tools in older people
• Especially the QALY* system, which is based on time
gained from death and quality of life.
• Is time an essential attribute at an advanced age?
• Do measurement tools capture what matters to older
people?
• Inclusion of outcomes related to carers?
*Quality-Adjusted Life-Year