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 16.9.13Jonathan Guillemot, PhD candidate, Institute of Gerontology, King’s College London

Jonathan.guillemot@kcl.ac.uk

Personal statement1. 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. Perspective on public health and context2. Epidemiology and burden of osteoporosis3. Existing management options4. Past and current clinical recommendations5. Past and current treatment consumption trends6. Explanations for the treatment gap7. 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 micro-architectural 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%

[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]

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

Anti-osteoporotic medications

Bisphosphonates

AlendronateIbandronateEtidronate

Zoledronate

SERM*Raloxifene

BazedoxifeneRANK ligand

inhibitors Denosumab

Parathyroid hormones

TeriparatidePTH(1-84)

Dual action bone agent

Strontium Ranelate

*SERM: Selective Oestrogen Receptor Modulator

3.2 Efficacy profiles

*Safety profile has since been questioned [9]

Management option [ref]

Reduction in incidence of fractures in osteoporotic women

Alendronate [1] 45%

Risedronate [2-3] 20%-50%

Zoledronate [4] 25%-70%

Ibandronate [5-6] 30%-40%

Denosumab [7] 20%-70%

Strontium Ranelate [8] 15%-40%*

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) (T-score< -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 (T-score< -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]

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

0

50000

100000

150000

200000

250000

300000

350000

400000

AlendronateRisedronateEtidronateIbandronateZoledronic acidRaloxifeneStrontium RanelateTeriparatidePTH

[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]

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

0

50000

100000

150000

200000

250000

300000

350000

400000

AlendronateRisedronateEtidronateIbandronateZoledronic acidRaloxifeneStrontium RanelateTeriparatidePTH

[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]

199819992000200120022003200420052006200720080

100000

200000

300000

400000

500000

600000

700000

800000

Total FRTotal UK

[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-union-medical-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]

• 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

UK

France

0 1000000 2000000 3000000

Treated Untreated

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)

[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+

65-74 75-84* 85+*0

1

2

3

4

5

France [1]England [2]

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 cost-effective 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-guidance-previous-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