Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management

The global burden of frailty has spurred an international effort to identify which instrument is most suited for frailty screening. An ideal screening tool needs to be effective not only in resource-limited areas, but also in developed countries where access to geriatric screening is often lacking. Frailty screening usually involves the recognition of functional decline alongside various other components which may or may not include slow gait speed, weight loss, cognitive difficulties, and exhaustion, depending on which screening tool is used.

Primary care appears to be the logical place to screen or case identify frailty in older persons (68, 69), particularly in its early stages when it is more likely to be amenable to intervention (28, 29, 31). However, many primary care practices (PCPs) are facing excessive patient loads, and must also divide their attention between diagnosing and managing chronic and infectious diseases that their older patients may present with. Further to this, many older adults have difficulties accessing health care services (70), which in turn is a major barrier to timely identification of frailty. Thus frailty should be identified in all healthcare encounters (33, 71).

A frailty screening instrument needs to be efficient in identifying frailty (72). Currently, there exists a large assortment of frailty screening instruments, each with a variety of included components. Screening tools recommended by the ICFSR task force include Rockwood’s Clinical Frailty Scale (CFS) (73), the International Association of Nutrition and Ageing (IANA)’s FRAIL scale (74), and the Edmonton Frailty Scale (EFS) (75). The CFS is based on clinical judgement, and involves a nine-point pictorial scale paired with corresponding text describing classifications of frailty (73). At scores higher than 6, an individual can be considered as having a disability in ADL rather than frailty per se. Recently, the International Consortium for Health Outcomes Measurement (ICHOM) has recommended the CFS as part of its standard set of outcome measurements for studies of older adults (76). The FRAIL scale comprises five components: Fatigue, Resistance, Ambulation (slow walking speed), Illness and Loss of Weight (5% or more in the previous year) and can be derived from pre-collected patient data (74, 77). It has been validated to predict poor outcomes such as disability and mortality, when disability is excluded from the original cohort (74). A treatment algorithm has been developed utilising its five components (78). FRAIL has been recommended in Australia as a screen for all older persons, where it can act as a “canary in the coal mine” (79); the Australian Government’s MyAgedCare website (the main point of entry into the aged care system), details information for older adults and aged care providers on how to use the FRAIL scale. The FRAIL scale is also predictive of physical limitation and mortality to a similar extent as the frailty phenotype of Fried and colleagues (80). The EFS includes nine components: functional limitation, self-reported health, general health status, cognition, social support, mood, functional performance, polypharmacy and continence (75), and is most commonly used in the hospital setting (81). It is also suitable for the community setting (82).

Many frailty screening instruments are well established as predictors of adverse outcomes such as mortality, functional decline and long hospital stays (3, 73, 83‐87). However, only low-certainty evidence has found that frailty screening is effective at informing treatment decisions and recovery expectations in a specialist setting (88). Indeed, the evidence-base showing that frailty screening leads to improved management of older people with frailty is lacking. This may be explained in instruments such as CFS by its focus on clinical diagnoses of disease and disability and, therefore, there is limited overlap with clinical frailty. In settings such as acute unplanned care, screening may actually have no influence on clinical decision-making regarding patient care and management (63, 89, 90).

Overall, there is a lack of current evidence to support systematic screening of frailty for all older adults, at least according to a 2018 comprehensive review (91). Many frailty screening instruments are also not validated for use in low-middle income countries (LMICs) based on a systematic review by Gray and colleagues (2016) (72).

A range of health practitioners may perform frailty screening, including geriatricians, PCPs, nurses, medical specialists and allied health professionals. It is important that health practitioners receive appropriate training on frailty screening. Importantly, some members of the patient consumer group suggested that older adults could also become empowered to identify frailty in themselves.

There are number of significant barriers to the implementation of frailty screening programmes, including a lack of public awareness of frailty, difficulties for older persons to access and afford primary care services, the acceptability of screening to older adults, and a lack of clarity regarding which treatment pathways should follow screening/diagnosis (70, 91). Primary care practices also face difficulties when adding an additional component to patient consultation visits.

Due to the very low certainty of evidence on the cost-effectiveness of frailty screening (92), it is unclear whether the benefits of frailty screening outweigh its cost. Evidence to support the cost-effectiveness of frailty screening comes predominantly from a recent clinical trial by Bleijenberg and colleagues (93) which reported that proactive screening for frailty in primary care was associated with a high probability of cost-effectiveness (85). However, a recent meta-analysis of the Dutch proactive approaches (which also included data from the study by Bleijenberg and colleagues) highlighted that frailty screening is not likely to be cost-effective (86).

Frailty can be clinically assessed using various criteria. The ICFSR recommended standard for clinical frailty assessment is the highly validated physical frailty phenotype, developed by Fried and colleagues in 2001 (37). An older person is classified as frail when three or more of these five components are present; pre-frailty is classified when one or two components exist (37). Moderate-certainty evidence has demonstrated that frailty assessment using Fried’s frailty phenotype is beneficial for older people with frailty.

It is important clinically to differentiate frailty from multi-morbidity and disability because management of these conditions differs. A Comprehensive Geriatric Assessment (CGA) (68) is too complex to be used as a frailty assessment tool and can miss frailty as it was originally designed to assess disability (and contributing medical conditions) in older adults before the concept of frailty existed clinically (95). Thus, CGA tends to be more disability- rather than frailty-centric. In addition, the quality of a CGA assessment depends on the time and quality spent on its application, and understandably there is likely to be much variation in quality and content. Further to this, CGA assessment can be costly to perform and may not be feasible in low resource settings (33). Notwithstanding this, a comprehensive management plan for older adults can be informed by a CGA (96), and an adapted CGA (68, 97) may be performed to identify any underlying causes of frailty.

Frailty assessment should be performed by a health practitioner who has had specific training in frailty assessment. This assessment is not limited to geriatricians, but also includes other medical specialists, PCPs, and allied health professionals who have undertaken geriatric training.

Genuine evidence on the effectiveness of a comprehensive management plan for frailty is emerging. An evaluation of the evidence-base found that a very low certainty of evidence existed regarding the effectiveness of individually tailored care plans for older adults with frailty. This evaluation was based on a recent systematic review (57), which covered three relevant clinical trials (99‐101). Importantly, an individualised care and support plan to manage frailty in older adults is endorsed in a recent report by the British Geriatrics Society (BGS), Age UK and the Royal College of General Practitioners (RCGP) (68).

Given the close link between reduced muscle strength and frailty, it is recommended that strategies for the management of sarcopenia are also adopted for older adults with frailty. The recent ICFSR guidelines for sarcopenia discuss specific strategies to improve aspects of sarcopenia (muscle strength, function, and muscle mass) (49). An additional benefit of focusing on the treatment of sarcopenia is that an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code has been recently awarded to sarcopenia (102, 103), which may be beneficial in terms of claiming for healthcare reimbursement, depending on the country.

Older adults with either frailty or pre-frailty should be assessed for fatigue causes. A recent large-scale study from both Dutch and Italian datasets (the Longitudinal Ageing Study of Amsterdam (LASA) and Invecchiare in Chianti (InCHIANTI) respectively) reported that exhaustion (fatigue) was the first frailty symptom to manifest in older adults (38). Major causal factors for exhaustion include: depression (102, 104); sleep apnea (105, 106); vitamin B12 deficiency (102); hypothyroidism (104, 105); anemia (107, 108); and hypotension (109).

A 2019 meta-analysis of 37 studies by Palmer and colleagues reported that 59% of older people with frailty are medicated with five or more medications (polypharmacy) (110). Medication management is recommended as part of a comprehensive management plan for frailty by the ICFSR task force. Appropriate de-prescription (medication withdrawal) to target polypharmacy is also recommended. A major point of contention with regards to de-prescribing in older people with frailty is the disagreement between pharmacists and clinicians regarding which medications to de-prescribe and how many should be de-prescribed (111). It is therefore recommended by the ICFSR task force that de-prescribing for older adults with frailty should occur using standard guidelines such as from the Screening Tool of Older Person’s Prescriptions (STOPP) criteria (112‐114) or Beers Criteria (116). The recent Asia Pacific clinical practice guidelines for frailty (33) and the best practice guideline report for the management of frailty (68) also support de-prescribing. Recently developed, although not yet externally validated, is a frailty-specific STOPP recommendation for use by clinicians (termed STOPPFrail), which outlines 27 criteria which of potentially inappropriate medications for older adults with frailty (114).

The task force recommendation to de-prescribe is based on a limited evidence base. The majority of systematic reviews of frailty interventions in community dwelling older adults have not focused on the effectiveness of de-prescription (56, 57). There is also a lack of evidence regarding the safety and effectiveness of medications in older adults with frailty (117).

Two systematic reviews specifically on older people with frailty have reported that:

Targeting polypharmacy for older people with frailty has been found to have no significant impact on mortality or other adverse outcomes, at least based on results from a recent RCT on de-prescribing in older Australians living in residential aged care facilities (RACFs) (n = 47 intervention; n = 48 control) (119). In this study, all RACF residents over 65 years were considered as frail.

All older persons with frailty should be assessed for visual and hearing difficulties and these should be corrected when present. Those who are at risk of falling should be checked for orthostatic hypotension and syncope (120).

Using GRADE methodology, very low certainty evidence revealed the multicomponent physical activity programmes (combining resistance-based training with aerobic and balance training) were effective at managing frailty in older adults. Recent systematic reviews which only include trials of frailty treatment (and not combined with frailty prevention trials) have reported that multicomponent training improved the outcomes of: muscle strength, balance, disability and falls in older adults with frailty (59‐61). To date, there is insufficient evidence that frailty or functional decline can be improved with multicomponent programs (59‐61), predominantly because very few trials actually measure these two variables at both baseline and follow-up.

There was insufficient evidence to identify the optimal frequency, intensity, time and type (FITT) of physical activity required to treat/manage frailty. Similarly, there was insufficient literature to determine the exact combination of training modes (aerobic, resistance and balance training) most effective for frailty management. Notwithstanding this, it is understood that for physical activity programs to be effective for those with frailty, a minimal level of intensity and an adequate program timespan are needed (122). Group physical activity sessions were more likely to be successful in improving frailty than individual sessions according to a recent systematic review (57), although this premise is based on only two trials which did not use qualified trainers.

Systematic reviews of physical activity for the treatment of frailty have specifically reported that:

There are additional systematic reviews covering the effects of physical activity for older persons with frailty, although these are limited by their merging of frailty prevention studies (no persons with frailty or pre-frailty at baseline) with frailty intervention trials (57), or by including studies defining frailty using outdated definitions such as “having multiple morbidities”, “resident of an aged care facility”, “dependent in ADL” or simply “aged 65 years and over” (124, 125).

Members of the patient consumer group advised that they would need guidance and support to undertake a physical activity program, with many preferring group-based classes. The majority of patient consumer group members also agreed that it would be very difficult to accomplish a physical activity program on their own. The importance of increasing physical activity and reducing sedentariness was also highlighted by members of the patient consumer group.

Moderate-certainty of evidence showed that older adults with frailty improve in their frailty status and physical performance when undergoing either progressive resistance-based training or a multicomponent physical activity program containing resistance-based training (57). Resistance-based training includes any physical activity which uses external resistance (such as from dumbbells, machine-based weight training, hydraulic resistance (water-based resistance training) elastic therapy bands, and body weight) to produce skeletal muscle contractions at levels higher than during routine activity (49).

The evidence-base on nutritional supplementation is heterogeneous in terms of study outcomes and firm conclusions cannot be inferred. Systematic reviews of protein and/or caloric supplementation have reported the following:

Overall dietary quality may influence the progression of frailty in older adults (53, 54, 131). For instance, low-level evidence from prospective cohort studies has demonstrated that a traditional Mediterranean diet can reduce frailty risk in community-dwelling older persons (132‐134). These findings were supported by a 2018 meta-analysis which reported that good adherence to a Mediterranean diet significantly reduced incident frailty [OR (95% CI) = 0-.47-0.82] (135). Lack of dietary nutrient quality may also accelerate the progression of frailty, with a recent systematic review reporting that micronutrients such as folate, β-carotene, and vitamins A, C and E associate with the development of frailty (136).

However, studies of dietary quality (including micronutrient intake) have focused primarily on the prevention of frailty development. What is not known is the effect of dietary quality for the treatment/management of already established frailty. Clinical trials involving older adults with frailty are therefore needed to form an evidence-base regarding the benefits of dietary quality for the management of frailty in older adults.

Treatable causes of weight loss can be identified by the MEALS-ON-WHEELS mnemonic (137, 138):

No members of the Spanish patient consumer group considered that supplements would be needed to treat frailty, with participants preferring to complement physical activity with a good, healthy diet, especially a Mediterranean diet. For the USA patient consumer group, the majority of members suggested that they would not use nutritional supplementation to manage frailty, although a few members were unsure and suggested that supplements could perhaps only be prescribed if diets were deficient.

Systematic review evidence indicates that oral health is associated with frailty, although the majority of research on the topic is from cross-sectional studies (142, 143). Older adults with frailty are more likely to have edentulism (reduced tooth number) and lower occlusal force (bite strength) (144). Recent longitudinal studies from Japan have reported that older adults with lower occlusal force/reduced chewing ability are significantly more likely to develop frailty (145, 146). Similarly, a study of British community-dwelling older people found that incident frailty was higher in older adults with edentulism, oral health problems or symptoms of dry mouth (147). However, there exists a shortage of clinical trials investigating the impact that improved oral health has for older persons with frailty.

Insufficient evidence exists regarding the effectiveness of pharmacological interventions for older adults with frailty. It is therefore not possible to evaluate whether the benefits of pharmacological intervention outweighs the risk of adverse outcomes such as unwanted side effects and patient burden. Notwithstanding this, several recent studies are paving the way forwards with regards to advancing drug development for the treatment of frailty (148). It has been proposed that pharmacological-based strategies may, in time, be beneficial to those older adults with frailty, particularly for those with co-morbid conditions which exacerbate frailty (148). However, at this point in time, both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) do not consider frailty to be an acceptable condition for a medication to be approved.

There exists many challenges for pharmacological trials for the management of frailty, including the lack of a standard measurement for frailty, and defining exactly who will be in clinical trials given the different conceptual understandings of frailty (148, 149). Perhaps most notable is that older adults with frailty may have co-morbid conditions, and clinicians are advised to use their own expert clinical judgement regarding the management of these conditions — noting that these conditions may indeed warrant specific pharmacological treatment/management regimes.

Frailty is associated with low levels of vitamin D in the majority of epidemiological studies (152). Recent meta-analysis evidence also suggests that 25-hydroxyvitamin D (25OHD) serum levels associate with frailty in a dose-response manner (153). However, insufficient evidence exists regarding the effectiveness of vitamin D supplementation for older adults with frailty. Indeed, there exists a distinct shortage of clinical trials which focus exclusively on frailty. Most vitamin D trials have targeted the generic population of older adults, with several systematic reviews on the topic reporting mixed results (154‐158). Furthermore, there is moderate certainty evidence that vitamin D supplementation decreases fall rate but likely does not influence falls risk, at least according to a recent Cochrane review of older adults in hospital or aged care facilities (159). Notably, dosing of vitamin D may be relevant for fall prevention among frail older adults. Several double-blind RCTs comparing vitamin D with or without calcium against placebo among frail older adults reduced the risk of falling with daily applications of 700 to 1000 IU vitamin D (160). However, several trials testing large bolus applications (monthly 60’000 IU (161) to 100’000 IU (162) of vitamin D or annual dosing of 300’000 IU (163) to 500’000 IU (164)) increased fall risk among frail older adults. In terms of improvements in functional outcomes, the evidence-base is inconsistent (155‐157). Further research is needed on the role of vitamin D supplementation in frailty prevention and treatment among older adults.

Social isolation is a major risk factor for the progression of frailty in older adults (167, 168). Older adults with frailty may need assistance in navigating their health care, and in performing instrumental ADLs (IADLs) such as medication management and grocery shopping. These difficulties are faced by all older adults (70), although are exacerbated with frailty (2). It is also important for healthcare providers to consider autonomy in processes of care and accessibility of healthcare services for older adults with frailty (169).

The impact on social support on outcomes in older persons with frailty is uncertain. An exploratory systematic review by Gardner et al. (62) reported that in older people with frailty/risk of frailty, the provision of practical social support showed evidence of potential effectiveness in enabling health-behaviour change compared with usual care (62). However, there was no evidence of effectiveness regarding other outcomes (health/social care use, mental health, general health, and health behaviour).