Series

Frailty 2
Management of frailty: opportunities, challenges, and future
directions
Elsa Dent, Finbarr C Martin, Howard Bergman, Jean Woo, Roman Romero-Ortuno, Jeremy D Walston

Lancet 2019; 394: 1376–86 Frailty is a complex age-related clinical condition characterised by a decline in physiological capacity across several
This is the second in a Series of organ systems, with a resultant increased susceptibility to stressors. Because of the heterogeneity of frailty in clinical
two papers about frailty presentation, it is important to have effective strategies for the delivery of care that range across the continuum of
See Editorial page 1298 frailty severity. In clinical practice, we should do what works, starting with frailty screening, case identification, and
Torrens University Australia, management of frailty. This process is unarguably difficult given the absence of an adequate evidence base for
Adelaide, SA, Australia individual and health-system interventions to manage frailty. We advocate change towards individually tailored
(E Dent PhD); Baker Heart and
Diabetes Institute,
interventions that preserve an individual’s independence, physical function, and cognition. This change can be
Melbourne, VIC, Australia addressed by promoting the recognition of frailty, furthering advancements in evidence-based treatment options, and
(E Dent); Population Health identifying cost-effective care delivery strategies.
Sciences, King’s College
London, London, UK
(Prof F C Martin MD);
Introduction increased susceptibility to stressors.4,7,8,10–12 When stressor
Department of Family Frailty is without question one of the most serious global events (such as acute illness) occur, a person with frailty
Medicine, McGill University, public health challenges we will face this coming cen­ rapidly deteriorates in functional capacity. Thus, inter­
Montréal, QC, Canada
tury. The rapid expansion of the ageing population has ventions to prevent or slow the progression of frailty
(Prof H Bergman MD);
Department of Medicine, brought a concomitant rise in the number of older adults before it leads to substantial functional decline are key
Chinese University of with frailty,1,2 which in turn places an increased pressure concerns for health-care policy and provision.
Hong Kong, Hong Kong, Special on health-care systems worldwide.3 Unfortunately, older In general, frailty is recognised as the physical state
Administrative Region, China
people with frailty have an increased likelihood of unmet that exists before occurrence of disability,7,8 although it
(Prof J Woo MD); Discipline of
Medical Gerontology and care needs, falls and fractures, hospitalisations, lowered is possible for frailty and disability to coexist.14 Frailty
Global Brain Health Institute, quality of life, iatrogenic complications, and early is also a dynamic entity that exists on a continuum
Trinity College, Dublin, Ireland mortality.4–9 This increased risk of adverse outcomes can from fit to frail,4,13,15 wherein an individual’s level of
(R Romero-Ortuno PhD);
occur even without the presence of comorbidities.4 frailty is able to change in either direction over time.7
Mercer’s Institute for Successful
Ageing, St James’s Hospital, Therefore, effective strategies that target the prevention Correspondingly, frailty is potentially reversible7,8 and
Dublin, Ireland and management of frailty in an ageing population will
(R Romero-Ortuno); Division of probably reduce the condition’s burden at the level of
Geriatric Medicine and Key messages
both the individual and the health system.
Gerontology, Johns Hopkins
School of Medicine, In reflection of increased research interest, the term • Although presence of frailty might seem like an ideal way
Baltimore, MD, USA frailty was introduced as a PubMed Medline Search to identify people who need additional support services,
(Prof J D Walston MD) Heading (MeSH) in January, 2018. Frailty is recognised there is a shortage of substantial research evidence to
Correspondence to: as an age-related clinical condition10–12 that is typically support this strategy and to identify the most effective
Dr Elsa Dent, Torrens University
observed by a deterioration in the physiological capacity instruments to detect frailty
Australia, Adelaide, SA, Australia
elsa.dent@adelaide.edu.au of several organ systems,4,8,12,13 and that causes an • In clinical practice, the management of an older adult with
frailty is complex because of the inadequate evidence base
for individual and health-system interventions to manage
Search strategy and selection criteria
the condition
We searched PubMed and the Cochrane Central Register of Controlled Trials for relevant • We need to accrue more knowledge about which
publications using combinations of several search terms: “frailty”, “frailty/therapy*”, intervention strategies are effective for frailty, and to
“patient care planning/standards”, “diet therapy”, “physical therapy modalities”, “drug determine whether they are feasible and cost-effective
therapy”, “therapy”, “aged”, “frailty/complications”, “frailty/diagnosis”, “geriatric • High quality clinical trials are needed that take into
assessment”, “frailty/metabolism”, “frailty/rehabilitation”, “micronutrients/ account the perspectives and needs of health-care
administration and dosage” and “clinical trials”. Searches were limited to work published providers, older people with frailty, and their carers
in English. We sought additional publications from the reference lists of identified papers, • In the absence of a firm evidence base for interventions,
and from the libraries of authors. To identify current and recently completed trials, we strategies to manage frailty in daily practice can be based
used the National Institute of Health’s ClinicalTrials.gov database. Where possible, the on existing consensus guideline recommendations
research cited in this Series was from systematic reviews and clinical trials published in the • It is important that frailty does not become a new aspect
previous 5 years, with the exception of key research publications. The literature search was of ageism that prevents access to interventions that could
done on Aug 27, 2018, and March 25, 2019. be appropriate

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its associated functional decline is also a potentially rate of functional decline observable in the last year before
preventable dis­ability.16 In many cases, frailty onset death,29 and the most functional dependence in activities
starts before age 65 years, although not all adults of daily living at 1 year before death.30 Once frailty is
develop frailty, even at advanced ages.4 Notably, the use established and progresses in its natural course, other
of frailty measurements for the purposes of prognosis geriatric syndromes are more likely to emerge, including
has recently emerged from geriatric medicine and falls, incontinence, rapid functional decline, pressure
into the medical specialties.9,17–19 What this means is ulcers, mild cognitive impairment, and delirium.12
that recognition of an individual’s frailty status can
inform treatment decisions, goals of care, and recovery Identification of frailty
expectations.20 Frailty instruments are prognostic across a broad
Over the past two decades, strategies to manage frailty range of medical interventions, including chemotherapy
have progressed substantially. However, to progress from doses,31 cardiology procedures,17,20 and abdominal sur­
traditional, episodic-based care to more proactive, person- gery.18 In long-term care facilities, these instruments can
centred care, we need to do much more. In this Series be used to grade severity of frailty, thereby identifying
paper, we provide a critical review of the evidence base individuals who might benefit most from a palliative
behind both individual and health-care system inter­ approach and advanced care planning.32 Relatedly, in the
ventions targeting individuals with frailty. With a noticeable acute care setting, frailty instruments can be used to
lack of high-quality research evidence regarding how best
to identify and treat people with frailty, we provide a
research-informed viewpoint of what strategies appear to Panel 1: Key terminology
work best. We acknowledge that although frailty can occur Frailty
in people of all ages (particularly if comorbidities are An age-related clinical condition, typically with deterioration in the physiological capacity
present), the majority of intervention trials involve older of several organ systems, that is characterised by an increased susceptibility to sudden,
populations. Hence, the focus of our review is on older disproportionate functional decline following stressor events.
adults, although findings might also be applicable to
younger people with frailty. This paper is the second in Frailty instrument
this Series on frailty, with the first paper overviewing A score or set of criteria used to identify frailty. The two most common frailty instruments
the concept of frailty, as well as its global burden, life- used in research and clinical practice are the physical frailty phenotype8 and the Frailty
course perspective, and potential targets for prevention. Index (FI) of accumulative deficits.21,22
An outline of termi­nology used in this Series is shown in Frailty phenotype
panel 1. For this review, we consider frailty as distinct from The phenotype model of frailty developed by Fried and colleagues considers frailty as a
advanced age, functional ability, and multimorbidity, even biological syndrome,8 and classifies an individual as frail when three or more of the
though it is related to these concepts. following five physical components are present: shrinking (unintentional weight loss of
4·5 kg or more in the last year), weakness (low grip strength), exhaustion (self-reported),
The natural history of frailty slowness (slow walking speed), and low physical activity.8 A classification of pre-frailty is
There is much heterogeneity in the course of physical given when only one or two of these physical components are present; robust is the
frailty in the absence of treatment, with different initial classification given to an individual who has no frailty components present.8
manifestations often leading to different trajectories
of frailty progression.12 Nevertheless, epidemiological FI of accumulative deficits
studies have reported commonalities with regards to Rockwood and Mitnitski’s FI represents an alternative viewpoint on frailty that
the first components of frailty to develop. For instance, incorporates the condition’s multidimensional nature; it is based on the degree of
on the basis of two large-scale cohort studies (the accumulation of 30 or more health deficits, which increase in prevalence (but do not
Longitudinal Aging Study Amsterdam with 15-year saturate) with age.21,22 Health deficits included are comorbidities, psychological factors,
follow-up, and the InCHIANTI study with 9-year follow- symptoms, and disabilities.21,22 The FI provides a score on a continuum from 0 (no deficits)
up), the first physical component of frailty that manifests to a theoretical maximum of 1 (all items exhibit deficits).21,22
tends to be exhaustion, followed by slow­ness of gait, Multimorbidity
lowered physical activity, and weakness.27 This result The concurrent existence of more than one medical condition in the same individual.23
does differ from earlier research from the Women’s
Health and Ageing Study II, which suggested that Disability
weakness develops first;28 although this difference could Defined by WHO’s World Report on Disability as “impairments, activity limitations and
be because of differing definitions of exhaustion.27 participation restrictions” affecting any of six domains: cognition, mobility, self-care,
What is consistent across the literature is that weight getting along (interacting with other people), life activities, and societal participation.24
loss tends to develop later than the other physical Comprehensive geriatric assessment (CGA)
components of frailty.27,28 A CGA is specialist, multidisciplinary, co-ordinated care that addresses the physical,
Moreover, the functional decline associated with frailty is mental, medical, and social needs of an older person with frailty.25 CGA was originally
gradual, incessant, and begins several years before death.29 developed to address disability, well before the emergence of the concept of frailty.26
Compared with other conditions, frailty has the slowest

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Components Frailty classification Setting

Primary Hospital Long-term
care care facility
Frailty phenotype8 Five items: weight loss, low physical activity, exhaustion, slowness, weakness Frailty: ≥3 items; pre-frailty: 1–2 items; Yes Yes Yes
robust: 0 items
Frailty Index21,22 30 or more accumulated health deficits: scores range from 0 (no deficits) to Continuous score; suggested cutoff score Yes Yes Yes
1 (all deficits) for frailty >0·2534
Electronic Frailty Index35 As for the Frailty Index, with variables derived from routine electronic health Severe frailty: score >0·36; frailty: Yes No No
records in primary care; also considered to be a case-finding instrument score >0·24–0·36; mild frailty:
score >0·12–0·24; fit: score ≤0·12
Clinical Frailty Scale36 Visual and written chart for frailty with nine graded pictures: 1=very fit; Frailty: score ≥5 Yes Yes Yes
9=terminally ill
FRAIL scale11 Five items: fatigue, resistance, ambulation, illness, loss of weight Frailty: ≥3 items; pre-frailty: 1–2 items; Yes Yes Yes
robust: 0 items
Study of Osteoporotic Three items: weight loss, exhaustion, unable to rise from a chair five times Frailty: ≥2 items; pre-frailty: 1 items; Yes Yes No
Fractures frailty criteria37 robust: 0 items
PRISMA-738 Seven self-reported items: age (>85 years), male, social support, and ADLs Frailty: score ≥3 Yes No No
Tilburg Frailty Indicator39 15 self-reported items in three domains: physical, psychological, and social Frailty: score ≥5 Yes No No
Geriatric 8 frailty Eight items: function (ADL and IADL), mobility, nutrition, comorbidity, Frailty: score ≤14 No Yes No
questionnaire for oncology cognition, depression, social support
(G8)40
Groningen Frailty Indicator41 15 self-reported items in four domains: physical, cognitive, social, psychological Frailty: score ≥4 Yes No No
Short Physical Performance Three measured items: gait speed, standing balance, and repeated chair stands; Frailty: score ≤9 Yes No No
Battery42 each item scored from 0–4, maximum score of 12
Edmonton Frailty Scale43 Nine items: cognition, health (2 ×), hospitalisation, social support, nutrition, Frailty: score ≥7 No Yes No
mood, function, continence
Multidimensional Eight items: comorbidity, nutrition, cognition, polypharmacy, pressure sore risk, Frailty: score >0·66; Yes Yes No
Prognostic Index44 living status, ADL, IADL pre-frailty: score 0·34–0·66;
robust: score <0·34
Kihon Checklist45 25 dichotomous items in seven categories: physical strength, nutrition, eating, Continuous score; suggested frailty cutoff Yes Yes No
socialisation, memory, mood, and lifestyle; scoring as per the Frailty Index score >0·25
Frailty Risk Score46 Formula: age (per 10 years) × 4 + male sex × 10 + no partner × 5 + body mass Very good: score <45; good: score 45–50; No Yes No
index <18·5 kg/m² × 12 + cardiovascular disease × 4 + diabetes × 4 + number of moderate: score 51–55; poor: score 56–61;
drugs ≥2 × 5, EMS<20 × 5 + ADL motor deficit × 4 + ADL process deficit × 7. very poor: score >61
Also considered to be a case finding instrument.
Hospital Frailty Risk Score47 109 summed items from ICD-10 frailty-relevant codes from administrative Low risk: score <5; intermediate risk: No Yes No
hospital data. Also considered to be a case finding instrument. score 5–15; high risk: score >15
EMS=Elderly Mobility Scale. ADL=activities of daily living. IADL=instrumental activities of daily living. ICD-10=International Statistical Classification of Diseases and Related Health Problems, 10th revision.
Derived and modified from Dent and colleagues, 2016.13

Table 1: Commonly used frailty instruments

assign triage categories to patients for the purposes of identified in all encounters with older people with mul­
referral to appropriate management plans.33 timorbidity.50 Additionally, England’s National Health
Many frailty instruments are in common use (table 1), Service general practice contract for 2017/201851 includes
with much variation in both their biological basis frailty identification as a requirement. Organisations
and their included components. This variation has focused on frailty, such as the Canadian Frailty Network52
sparked intense research and debate as to which frailty and the Asia-Pacific Clinical Practice Guidelines for
iden­tification instrument is best for clinical practice. the Management of Frailty,49 have also recommended
By and large, when selecting an ideal frailty instrument, that all older people should be screened for frailty during
a clinician needs to consider the instrument’s validity health-care encounters.
across the setting of interest, as well as its ultimate However, there is no robust evidence yet to support
purpose (for example, risk assessment in clinical routine frailty identification as a means to improve
practice).48,49 clinical care and cost-effectiveness in older populations.53
Because of the substantial challenge that frailty places Results of frailty screening and case finding may in
on health-care systems, effective and pragmatic screening fact have no influence on physician decision making
or case finding is often recommended as a first step in regarding patient management, at least based on studies
the process of frailty management. in the acute care setting.33,54 Following from this, many
In England, the National Institute for Health and Care frailty instruments often have low completion rates in
Excellence (NICE) has advised that frailty should be clinical practice,33 rely heavily on proxy input,55 and can

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lack reliability in specific settings,55 and it is often not instrument to identify frailty. Also excluded were
clear which frailty instrument should be applied reviews that combined results of studies on both treat­
in which setting.13,20 To compound these issues, various ment and prevention, noting that older adults with
frailty instruments do not identify the same individuals frailty might respond differently to interventions than
or predict the same adverse outcomes.4,56,57 Thus, those without.
although frailty identification may seem like an ideal On the whole, the evidence suggests that although
strategy to identify someone who is in need of additional several interventions have yielded positive outcomes
support services, there is currently a lack of substantial compared with usual care, the certainty of evidence
research-evidence to support the effec­tiveness of this was either low or very low for all outcomes analysed,
strategy and to identify the most effective frailty indicating that further investigation is required to
instruments. ascertain effectiveness of interventions. Table 2 covers
three settings: all community-dwelling people (screening
Evidence from clinical trials targeting the and case identification in primary care); community-
individual dwelling older people living with frailty (home and
Table 2 outlines several individual strategies used for community interventions); and older people with frailty
the management of people living with frailty, all of in the hospital setting. The first of these settings is
which have been shown to be superior to usual care in discussed earlier in this paper and in the first paper in
recent systematic and structured reviews. We excluded our Series; the other two settings are discussed below.
sys­tematic reviews that did not use a validated frailty No systematic reviews identified positive interventions

Evidence Outcomes analysed Certainty of evidence

All community-dwelling older adults (primary care)
Identify frailty or pre-frailty through Four systematic reviews58–61 Accurate identification of frailty or pre-frailty Low
screening and case identification in
primary care
Community-dwelling older adults living with frailty (interventions targeting the management of frailty in home or community settings)
Prescribe physical activity programmes Three systematic reviews62–64 (excluded: reviews on frailty Physical performance (SPPB); gait speed; muscle Very low for all four outcomes
(resistance-based training, aerobic training, prevention or with merged frailty and pre-frailty groups65–67) strength; mobility
or balance or coordination training)
Prescribe multicomponent physical Three systematic reviews62–64 (excluded: reviews on frailty Disability; falls; balance; muscle strength Very low for all four outcomes
activity programmes prevention or with merged frailty and pre-frailty groups 65–67)
Provide community-based group physical Systematic review of six trials of mild frailty or pre-frailty,68 Physical function; muscle strength; balance Very low for all three outcomes
activity classes and one systematic overview with one relevant trial69
Protein or protein-energy, micronutrient Systematic review of three nutritional trials,66* and Frailty; physical performance; strength (leg or grip); Low for all five outcomes
supplementation one systematic overview with one relevant trial69 gait speed; physical activity
Provide individually tailored management Systematic review of three trials of frailty66* Frailty; ADL Low for both outcomes
of clinical conditions
Provide advice on health behaviour Systematic review of six education trials70 Physical function Low
improvement
Ensure practical social support Systematic review of 13 trials on enabling health-behaviour Physical function Very low
change70
Modify home environment for health Systematic review of five trials70 Physical function; health behaviour Very low for both outcomes
behaviour change
Older adults with frailty in hospital (hospital care)
Ensure targeted care delivery through CGA Systematic mapping review of eight studies covering CGA Physical function; readmission; emergency Very low for all outcomes
intervention (CGA done in emergency intervention for older people with frailty33* department readmission
department, short stay unit, or clinical
decision unit)
Review medications using implicit criteria One systematic mapping review33* Prevention of emergency department readmission Very low
Ensure patient is placed on a frailty-specific One systematic mapping review33* Prevention of emergency department readmission Low
care pathway
All intervention strategies listed in this table have been reviewed for effectiveness in recent systematic and structured reviews; intervention strategies without systematic review appraisal were not included.
Reviews were only listed if their included studies defined frailty using objective measurement, regardless of whether they had the word frail in their title. All strategies and outcomes listed have been found to be
superior to usual care; strategies and outcomes not showing consistent or substantial evidence of benefits compared with usual care have not been included. Certainty of evidence was defined according to
GRADE criteria71 as applied by the authors: high (further research is very unlikely to change our confidence in the estimate of effect and there are no suspected biases); moderate (further research will likely change
our confidence in the estimate of effect and may change the estimate); low (further research is very likely to have an important impact on confidence in the estimate of effect, and is likely to change the
estimate); very low (any estimate of effect is uncertain). The search for relevant reviews was based on a quasi-systematic review, and thus the list of interventions might not be exhaustive. CGA=Comprehensive
Geriatric Assessment. ADL=activities of daily living. IADL=instrumental activities of daily living. SPPB=Short Physical Performance Battery test. *Although these systematic reviews combined results from older
adults in general and those with frailty, this table shows trial results for those with frailty only.

Table 2: Single strategies superior to usual care for management of frailty, by target population

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for older people with frailty residing in long-term care seem to re-test for frailty post-intervention.72 When older
facilities.69 adults with pre-frailty are considered, community-based
group physical activity classes seem to improve physical
Interventions in home and community settings function, although again, the evidence base is thin.68
Compared with usual care, single-mode physical activity A recent meta-analysis suggested that nutritional
programmes (resistance-based training, aerobic training, supplementation for frailty improves physical perfor­
or balance and coordination training) were reported mance and muscle strength, yet is ineffective for
to improve gait speed, muscle strength, mobility, and improving body-mass index or body weight;66 the evidence
physical performance in older people with frailty (table 2). base here was reported as of moderate-level certainty.
Similarly, multicomponent physical activity programmes However, this certainty of evidence could be inflated,
and group exercise classes both improved participant given that the evidence consisted of only three small-scale
muscle strength and balance. However, the evidence base clinical trials, which had inherent randomisation issues,
to support these findings was of low to very low certainty, high attrition rates, and a lack of blinding of study
indicating that future research is needed to truly gauge personnel.66
effectiveness in this context. There was insufficient evidence to gauge the effect
The optimal programme mix for physical activity is not of hormone therapy, cognitive training, or telehealth
yet known, with studies showing much variation in the monitoring on either outcome improvement or frailty
frequency, intensity, type, and duration of exercise.62–64 reduction.66,68 Similarly, there is no evidence from
In terms of outcomes, there is insufficient evidence to randomised con­trolled trials on reduction of unnecessary
gauge whether physical activity programmes can improve medications in individuals with frailty.68 There is a
frailty or functional ability, predominantly reflecting the paucity of published evidence on pharmacological inter­
paucity of trials that include these two important outcome vention for the management of frailty.49,73,74
measures. Furthermore, physical activity trials do not
Hospital care
Hospital care for older people with frailty is an expensive
Panel 2: An example of a potential care plan for an older person living with frailty and lengthy process, often encompassing multiple
A comprehensive strategy to guide the treatment of an older person living with frailty hospital admissions and intervention strategies.33 Single
encompasses several strands, each with a distinct rationale, applied in accordance with strategies that are useful for the management of frailty in
the situation and priorities of individual people: the hospital setting are outlined in table 2.
• Reversing (or slowing progression of) the features that characterise physical frailty: In the acute care setting, medication review and
weakness, slowness of gait, unintentional weight loss, fatigue, and low physical use of a frailty-specific care pathway might prevent
activity levels.8 The clinical rationale is that these factors directly result in lost capacity, emergency department readmission;33 however, the
such as impaired activities of daily living and instrumental activities of daily living evidence here is only of low or very low certainty
(eg, weakness), are predictive of future losses (low physical activity), or reduce the (table 2). Targeted care delivery through implementation
resilience of the individual faced with a new external stressor. of Comprehensive Geriatric Assessment (CGA) appears
• Identifying and optimising the management of comorbidities and their associated to improve physical function, but not reduce emergency
medications. The rationale here is that common conditions associated with frailty, department readmission,33 with a low or very low
such as renal impairment or cardiovascular disease, could drive progression of frailty certainty of supporting evidence. Insufficient evidence
through biological (eg, inflammation) and behavioural mechanisms (sedentariness) exists to estimate the influence that CGA has on other
and independently contribute to functional limitations and poor quality of life. outcomes specific to older adults with frailty in the
• Identifying and addressing other losses of intrinsic capacity (such as vision and acute care setting. However, when older adults as a
hearing impairment, or low mood and affective problems) that contribute to the whole group are considered, use of CGA on admission
severity of frailty. The rationale is that functional ability is the product of the might reduce the likelihood of readmission75 and post-
accumulated impact of these common losses in the context of the individual’s hospital mortality rates.25 Indeed, CGA has been found
interaction with their total environment. to work well in populations of older adults (including
• Assessing an individual’s priorities and psychosocial resources, which can affect social those with frailty) when applied in specialist geriatric
functioning and quality of life. medicine wards,25 although more evidence specific to
• Crucially, appreciating the attributable contributions of frailty and individual frailty is needed in the acute care setting.
conditions to the outcomes of interest to the older person, assessing the potential for In the surgical setting, clinical trials are emerging
modifying these factors, and estimating the likely benefits, risks, and burdens of with mixed results regarding clinical outcomes.76–78 In
pharmacological and non-pharmacological treatments. Informed consent requires the medical specialties of orthogeriatrics and cardiology,
these estimations to be made explicit. to our knowledge, no clinical trials (excluding screening
• Promoting the achievement of generic older adult physical activity recommendations interventions) have explicitly focused on interventions
coupled with targeted additions such as reducing sedentary behaviour85 and to improve outcomes for patients with frailty. In
improving strength and balance to prevent falls seems a reasonable approach, at least oncology, there has been a call-out for trials in older
in people with pre-frailty. adults with frailty,79 reflecting the shortage of trials for
this population group.

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Additional considerations concerning clinical trials Columbia (Canada) guidelines for the early identification
Overall, the variable methodological quality of studies and management of frailty,74 and the Asia-Pacific guide­
across care settings and specialties provides a sparse lines for the management of frailty35 all provide strategies
evidence base for the clinical management of frailty. to manage frailty. Importantly, all recent consensus-based
Cost effectiveness is rarely studied, and intervention guidelines have included physical activity and adequate
outcomes are rarely person-centred. Such knowledge is protein intake as first-line therapies for the management
vital to add evidence-based clinical value to treating of frailty.49,50,73,74,80
older people with frailty. In cases where frailty has manifested from an under­
Several fundamental barriers need to be overcome lying medical condition or treatment for that condi­tion,
to improve the robustness of clinical trials on the pharmacological treatment for these conditions is para­
management of frailty. First, older people with frailty are mount.81 Regarding deprescription, consensus-based
often excluded from clinical trials, despite being the guidelines for frailty35,73,74 recommend that inappro­
population group that often uses the treatments being priate medications be deprescribed using standard
studied. Second, when trials are undertaken, recruiting approaches35,73,74 such as the Screening Tool of Older
and retaining participants is complex. For example, the Person’s Prescriptions criteria,82 or Beer’s criteria.83
National Institute of Health’s clinicaltrials.gov database However, the benefit-to-risk ratio of deprescription is not
shows that trials on frailty are still in recruitment or stalled clear, and the quality of studies on the topic is low.84
mode for substantial lengths of time. Finally, negative trial Panel 2 outlines an example of potential goals and
findings are often not disseminated in a timely manner. strategies of care for an older person with frailty. Collating
Addressing these issues will undoubtedly progress the these care strands into an integrated and person-centred
research field forwards. clinical management plan to be agreed with the patient
themselves is a skilled task that can necessitate an inter­
Potential goals and strategies of care disciplinary approach over several encounters. When
The management of frailty is not limited to physical and addressing frailty, an individual’s preferences, priorities,
psychosocial domains.73 The objectives of clinical care for and psychosocial resources should be incorporated into
people with frailty are to maintain functional independence their care management plan; these factors have an
and quality of life, while avoiding unnecessary admissions influence on an individual’s quality of life.80 Allied health
to hospital or long-term care facilities.73,74 Major evidence professionals can deliver interventions currently offered
gaps in treatment strategies can be filled with existing for the clinical management of frailty.
consensus guideline recommendations. For example,
NICE guidelines for multimorbidity encompass recom­ Interventions focusing on health-system targets
mendations for the clinical management of people with To manage the complexity of frailty and its array of
frailty,50 and WHO’s “Integrated Care for Older People associated factors, it seems logical to offer multi-
(ICOPE)” guidelines document provides strategies to component intervention packages at the public health
maintain and improve a person’s Intrinsic Capacity and system levels (table 2). Theoretically, these packages
(physical and functional capacity), which is applicable will achieve their desired outcomes if their component
to individuals with frailty.80 Likewise, consensus-based strategies are implemented effectively. However, in
guidelines from the British Geriatric Society/Age practice, success rates of such packages have been
UK/Royal College of General Practitioners,73 the British underwhelming,86–88 which could perhaps reflect good

Intervention Result
Kusatsu, A focused effort over 10 years to screen for frailty in primary care, with those identified as pre-frail or frail referred to Substantial functional improvements in the population91
Japan a group community programme involving physical activity, nutrition, and social participation91
Hong Kong The Hong Kong Jockey Club CADENZA project implemented a community frailty prevention project that has had Not yet evaluated in the academic literature
a strong response rate;92 the project has been running for over 9 years and involves the integration of health
and social care, provision of caregiver support, and community group classes involving physical activity92
Canada The Seniors’ Community Hub93 builds capacity in primary care to address the health and social needs of older adults Improvements in quality of life and functional maintenance
with frailty, including encompassing the needs of the older person with frailty in terms of their intrinsic capacity and or improvements in people with frailty93
frailty levels
UK The NHS General Practice contract for 2017–18 requires practices to identify adults aged 65 years and older with Effects on clinical outcomes have yet to be evaluated,
severe or moderate frailty according to an eFI based on routine primary care coding; this identification is paired with and might help to clarify whether the eFI is generalisable to
a clinical review incorporating medication and falls reviews, and activation of a care summary record51 primary care in terms of acceptability, feasibility,
interpretation, and implementation60
Singapore The Ministry of Health has implemented a Silver Generation Ambassadors programme, which integrates health Not yet evaluated in the academic literature
and social services to support seniors, specifically targeting older adults with frailty94
NHS=National Health Service. eFI=Electronic Frailty Index.

Table 3: Selected examples of frailty-specific interventions that focus on health-system targets, by location

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usual care (including primary care services) in countries have been designed to promote equity and a continuum
where interventions have been delivered.89,90 of care, and are promising examples of strategies that
Another factor might be that many intervention could work. Notably, most intervention trials for frailty
packages aim to achieve multiple outcomes, which have focused on individual-level interventions; very
although seemingly pragmatic, can lead to undesirable few intervention trials exist on health-system based
consequences. For instance, resources might be spread improvements.
thin, outcome prioritisation can become difficult, and the At the system level, successful management of frailty
intervention package can become too complex to roll requires a simple, clearly defined, low-cost strategy that
out as originally planned. In turn, complex intervention can be easily adopted by health-care policy makers.
packages run the risk of only being partially imple­mented Unfortunately, the few studies that have investigated cost-
because of time constraints and other difficulties faced by effectiveness have not shown prom­ ising results.86,88
both health professionals and older people with frailty.90 Recently, two systematic reviews highlighted that inter­
Nonetheless, there are several examples of success­ ventions based on the identification of frailty could lead to
ful community-based long-term frailty intervention recognition of unmet need and increased engagement
packages, as outlined in table 3. These interventions with health-care professionals and home care services.33,53

Panel 3: Proposed strategies to address evidence–practice gaps for the clinical care of frailty
Expand knowledge of pathophysiology and natural course Assess effectiveness of routine screening for older adults
of frailty with frailty
• More physiological-based studies that identify precise • Evaluation of whether frailty screening adds value to the
biomarkers of frailty clinical care of an older adult with frailty
• Studies which better articulate links between biological • Identification of when and where screening is best applied
changes and changes in organs and tissues that drive frailty
Identify the best instrument to detect frailty across settings
and vulnerability
• Need for an international consensus definition for frailty,
• Cross-cultural, large-scale, longitudinal cohort studies
rigorous validation studies, and cross-cultural studies
Enhance clinical care of older adults with frailty • Recognition that pursuit of this goal should not detract
• More efficient care delivery strategies which focus on both from other research priorities, such as identifying strategies
the equity and continuum of care for best clinical care
• Evidence-based clinical practice guidelines for specific
Expand knowledge of how to prevent frailty in
settings (primary care, acute care, rehabilitation, oncology,
community-dwelling older adults (and middle-aged adults)
cardiology, surgery), which in turn need a stronger evidence
• Targeting of risk factors of frailty to determine which
base for their formation
strategy is most effective
• Improvements in health-care accessibility (including
• Research into effectiveness of system-level interventions,
affordability, acceptability, availability) to decrease gaps
particularly in low-to-middle–income countries
between who needs treatment and who receives treatment
• More evidence of how to manage frailty and people with Expand scope of intervention research
frailty, including around the organisation of services, • More rigorous research into dietary patterns such as the
cost-effectiveness and the effectiveness of specialty care Mediterranean diet
• Knowledge translation studies (including process evaluation • High quality research into the role of oral health and
methodology) investigating barriers and enablers to sedentary behaviours in management of frailty
intervention success in everyday practice
Reform health care, including improvement of health-care
Improve methodological quality of clinical trials service coordination
• Person-centric metrics (patient reported outcome • Education and training programmes for health-care
measurements; patient reported experience measurements) professionals designed to improve the knowledge and
• Standard sets of outcomes across studies (eg, from the recognition of frailty
International Consortium for Health Outcomes • Health-care policies which promote quality of care for older
Measurement)104 people with frailty
• Cost-effectiveness evaluations • Clinical indicators for frailty
• Efforts to reduce bias • Health-care policy that targets the recognition and
management of frailty in everyday practice
Broaden scope of interventions to health-care system
targets and strategies
• Study designs that promote the implementation of
community-based frailty intervention packages (eg, an
interrupted time series design, or a trial within cohort design)

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For instance, earlier home discharge from hospital might

mean that more home services are needed.95 In addition, Age-related changes
many system-level interventions for frailty focus on • Mitochondrial dysfunction
• Neurodegeneration
reducing hospital readmissions, and consequently, • Cellular senescence
individuals may be displaced to health-care settings • Stem cell decline
• DNA methylate and damage
considered more appropriate for their care needs.33 This • Autophagy abnormalities
Altered energy metabolism
displacement seems to be towards primary care, and its Geriatric
extent, cost, and clinical implications are not yet known.33 Stress responsive impairment syndromes
• Chronic inflammation
It is therefore reasonable to propose that general Genes and environment
Disability
• Cognition • HPA axis Physical
practitioners should be provided with support when • Nutrition • Autonomic nervous system frailty
Mortality
designing and implementing system-based inter­vention • Activity
Neurological decline
packages for frailty. Cognitive
impairment
In principle, much of the management of people with Anabolic hormone and decline
Chronic diseases
frailty can make use of clinical care initiatives already • Cardiovascular disease
in existence for older adults with non-communicable • Hypertension
• Arthritis
diseases or complex care needs. For instance, compre­
• Diabetes
hensive care packages and the use of multidisciplinary care • Obesity
teams are applicable to older adults with frailty and make
use of existing resources and infrastructure. Nonetheless, Figure: Model pathway for physical frailty
limited research exists on the feasibility and cost- Reproduced from Michel et al107 by permission of Oxford University Press. HPA=hypothalamic-pituitary-adrenal.
effectiveness of this strategy, and many low-to-middle
income countries might not have such care pathways. In Examples of the most urgently required strategies are:
the future, intervention packages that facilitate inde­ high quality clinical trials with a broadened focus on
pendence, such as re-enablement and restorative care, health system targets and strategies; robust evidence on
could become crucial.96 Moreover, since the implementation how to best manage frailty (including cost-effectiveness
of frailty intervention packages faces many challenges and and the effectiveness of specialty care); and efficient care
uncertainties, alternative strategies that remove community delivery strategies. We also need to derive precise
barriers to care services are needed, including a greater biomarkers of frailty that will facilitate the development
knowledge and understanding of accessibility issues that of more precise treatment strategies.
older adults with frailty face when accessing health and
social care services. Personalised medicine
In older adults with frailty, personalised (person-centred)
Implementing frailty identification in clinical medicine provides a strategy to target the treatable causes
practice of frailty, support early identification, and promote infor­
Health practitioners need to be aware of the great med decision-making.105 This personalised strategy can
responsibility faced by caregivers of older adults with address individual variations in lifestyle and genetic
frailty.97 Recent work has also highlighted the importance factors, which might improve patient care.105,106 The figure
of identifying the social support networks, resilience, and illustrates a conceptual framework by which basic cellu­
coping skills of older adults with frailty;98–100 these health lar ageing processes, in combination with environmental,
assets can be used to ameliorate the challenges that genetic, and chronic disease states, act together to drive
frailty presents. The implementation of frailty iden­ the development of the physical frailty phenotype. In
tification in clinical practice should also take into future, an understanding of ageing-related biological
consideration the potential burden of labelling an older changes in older adults, such as mitochondrial changes,
adult as frail.101 In the absence of evidence-based stem cell decline, and senescent cell emergence, will be a
interventions for frailty, screening might inadvertently crucial next step for the management of frailty.108
contribute to biasing clinicians and negatively influ­ However, there are many challenges to developing
encing patients’ behaviour.102 Further­more, older adults effective personalised medicine for someone with frailty.
themselves consider frailty to be an irreversible condi­ Foremost, frailty is unarguably complex. To successfully
tion,103 and in turn, might not wish to be acknowledged as prevent or treat frailty, we must appreciate its complex
frail. Indeed, it is important that frailty does not become underlying biological processes, many of which are not
an aspect of ageism that prevents access to potentially yet clearly known. If it takes many decades to develop
appropriate interventions.15 personalised medicine approaches to target single-gene
diseases,106 it will inevitably take much longer to develop
Future directions a successful, personalised strategy to target the multiple
Closing gaps between evidence and practice organ systems that associate with frailty. Furthermore,
Possible strategies to close gaps between evidence and there is much heterogeneity in prognosis and response
practice in the field of frailty are outlined in panel 3. to treatment in those with frailty, which in turn reduces

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accuracy in predicting which individuals will or will not 7 Junius-Walker U, Onder G, Soleymani D, et al. The essence of
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discussed give hope that the next generation of frailty Systematic review and meta-analysis of frailty as a predictor of
management will improve the health outcomes of older morbidity and mortality after major abdominal surgery. BJS Open
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people living with the condition, as well as promote 19 Handforth C, Clegg A, Young C, et al. The prevalence and outcomes
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20 Rajabali N, Rolfson D, Bagshaw SM. Assessment and utility of
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Contributors Can J Cardiol 2016; 32: 1157–65.
ED was part of the team that coordinated the Series, and she performed 21 Rockwood K, Mitnitski A. Frailty in relation to the accumulation of
the final editing of the manuscript before submission. All coauthors deficits. J Gerontol A Biol Sci Med Sci 2007; 62: 722–77.
drafted key sections of the manuscript. All authors have edited the paper 22 Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits
for intellectual content and approved the final version of the paper. as a proxy measure of aging. Scientific World Journal 2001;
1: 323–36.
Declaration of interests 23 WHO. Multimorbidiy (2016). https://apps.who.int/iris/
We declare no competing interests. handle/10665/252275 (accessed Oct 1, 2018).
Acknowledgments 24 Federici S, Bracalenti M, Meloni F, Luciano JV. World Health
ED is supported by an Australian National Health and Medical Research Organization disability assessment schedule 2.0: an international
Council (NHMRC) Early Career Fellowship [grant number: 1112672]. systematic review. Disabil Rehabil 2017; 39: 2347–80.
We thank Ahmed Negm, (University of Alberta, Canada) for his 25 Ellis G, Gardner M, Tsiachristas A, et al. Comprehensive geriatric
invaluable advice on table 2. We are grateful to Denis Marin (Queensland assessment for older adults admitted to hospital.
Cochrane Database Syst Rev 2017; 9: CD006211.
University of Technology, Australia) for his work structuring and editing
the manuscript. Finally, we acknowledge the input of Emiel O Hoogendijk 26 Solomon D, Brown A, Brummel-Smith K, et al. National Institutes
of Health Consensus Development Conference Statement:
in the planning, development, editing, and review of our manuscript.
geriatric assessment methods for clinical decision-making.
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