Primary care service use by end-of-life cancer patients: a nationwide retrospective cohort study in the United Kingdom

Background End of life(EoL) care becomes more complex and increasingly takes place in the community but there is little data on the use of general practice (GP) services to guide care improvement. This study aims to determine the trends and factors associated with GP consultation, prescribing and referral to other care services amongst cancer patients in the last year of life. Methods A nationwide, retrospective cohort study using the Clinical Practice Research DataLink(CPRD) in the United Kingdom primary care, 2001-2014. Outcome variables were number of GP consultations(primary), number of prescriptions and referral to other care services (yes vs no) in the last year of life. Explanatory variables included socio-demographics, clinical characteristics and the status of palliative care needs recognised or not. The association between outcome and explanatory variables were evaluated using multiply adjusted risk ratio(aRR). Results Of 68,523 terminal cancer patients, 70% were aged 70+, 75% had comorbidities and 45.5% had palliative care needs recognised. In the last year of life, a typical cancer patient had 43 GP consultations (Standard deviation(SD): 31.7; total=3,031,734), 71.5 prescriptions (SD: 68.0; total=5,074,178), and 21 (SD: 13.0) different drugs; 58% of patients had at least one referral covering all main clinical specialities. More comorbid conditions, prostate cancer and having palliative care needs recognised were associated with more primary care consultations, more prescriptions and a higher chance of referral (aRRs 1.07-2.03). Increasing age was related to fewer consultations (aRRs: 0.77-0.96), less prescriptions(aRR 1.09-1.44), and a higher chance of referral (aRRs 1.08-1.16) but less likely to have palliative care needs recognised(aRRs 0.53-0.89).

the importance of enhancing primary palliative care skills among GPs and the imperative of a greater integration of primary care with other healthcare professionals including oncologists, palliative care specialists, geriatricians and pharmacists. Research into the potential of deprescribing is warranted. Older patients have poorer access to both primary care and palliative care need to be addressed in future practices.

Background
End of life (EoL) care refers to care that is provided and delivered in the last year of life, which accounts for approximately 10 to 20% of healthcare costs [1]. As we live longer with more comorbidities, the complexity of need at the end of life is bound to increase. This coupled with the projected rise in numbers of people dying with cancer over the next two decades and people's preference to be cared for and die at home or in a home-like environment [2,3], highlights the importance that providing quality care and support to people with terminal cancer in the community care settings. It is also a policy priority for health care in many countries [2,4,5].
General practitioners (GPs, or family/primary care doctors), the primary care providers in the community, play an important role in EoL care which include, for example, care planning and coordination, and providing continuity of care. However, even in the United Kingdom (UK), where the quality of death ranked the best in the world [6], the EoL care is far from optimal. In a recent survey of bereaved people, one in four rated the overall quality of EoL care for their relatives as poor or fair. Care quality from GPs came as the second worst service provider among the 7 providers surveyed, with 30% poor or fair ratings, next to urgent care [7].
As GPs not only deliver end of life care but also act as a gatekeeper for patients to access other health care services, how patients interact with GP services has a direct impact on their access to other healthcare services and with implications for health outcomes [8].
However, there is little data on the service use of primary care by end of life cancer patients, although this forms an essential step to understanding and identifying problems and gaps in service provision. Furthermore, palliative care is a care provided to seriously ill patients that aims to improve quality of life and reduce suffering. It is a holistic approach of care and deemed more appropriate for patients at the end of life. Primary care providers are particularly well positioned to deliver primary palliative care. It is unclear if a patient's palliative care needs known to their GPs plays a role in the primary care service use of the patient.
Therefore, we developed this study in the UK primary care and aimed to: 1) describe the patterns of primary care service use among cancer patients in the last year of life, 2) evaluate the role of recognising patients' palliative care needs in primary care service use, and 3) identify patient characteristics associated with the use of primary care services and with patients palliative care needs recognised by their GPs.

Study design and Setting
A nationwide, population based retrospective cohort study in UK primary care, 2001-2014.

Data sources
The data were extracted from the Clinical Practice Research Datalink (CPRD) -one of the world's largest longitudinal primary care databases [9]. By the mid-year of 2013, the CPRD contained anonymized primary care health records for 4.4 million active (alive, currently registered) patients from 7.2% (n=674) of all UK general practices. Patients are broadly representative of the UK general population in terms of age, sex and ethnicity. The CPRD contains data generated during the process of health care in general practices, with demographics, and longitudinal information on clinical aspects (e.g. diagnoses, symptoms, comorbidity), GP contacts, prescriptions, management and referrals and so on. CPRD has been widely applied to health service research.

Patient cohort
The inclusion criteria were patients who: 1) were diagnosed with a common cancer, as ascertained by Read codes (Lung -B22; Colorectal -B13, B14, B1z0.11; Female breast -B34, B36..00; Prostate -B46); and 2) had at least 6 months of registration with the practice before the cancer diagnosis; and 3) died between 01/01/2000 and 30/04/2014 inclusive; and 4) were registered at a general practice with acceptable data quality.
Patients who did not have a clear diagnostic code were excluded.

Study variables
The outcome variables were the service use in the last three months of life in three main categories: a) GP consultations (primary), b) medicines prescribed (using the CPRD unique product codes selected by GPs) and c) referral to secondary care or other care services.
We included consultations involving patient contacts, either through face-to-face or telephone, irrespective of where the consultations taking place. We excluded the palliative care referral as this was used to identify patients having palliative care needs recognised (detailed as below).
The explanatory variables were: 1) socio-demographics -age (<50, 50-59, 60-69, 70-79, 80-89, 90+), gender (female, male), year of death, the region where the patient registered general practice was based; 2) clinical variables -cancer site (lung, colorectal, breast, prostate), number of comorbid conditions (0,1, 2, 3, 4+), survival (months) from cancer diagnosis to death (0-5, 6-12, 13-36,37-60, 61-120, 121+), the status of having palliative care needs recognised (PC group) or not (non-PC group) following the cancer diagnosis. A patient who was either on the palliative care register or had a referral record of palliative care after their cancer diagnosis was categorised as having palliative care needs recognised. The Quality and Outcomes Framework (QOF) was first introduced as part of the new General Medical Services contract in 2004. [10] The QOF incentivises general practices to identify and register patients with palliative care needs, regularly review, assess their needs and preferences and proactively planning care. Palliative care was endorsed as a new clinical area for improvement from 2006. The needs of palliative care were identified by Read codes (See Appendix 1 QOF_codes.txt). The palliative care referral was identified using the National Health Service (NHS) specialty field. This contains detailed information about the referring speciality but its completion by general practice staff is not compulsory.
The socio-economic status, measured by the quintile of the index of multiple deprivation (IMD2010) (1=least deprived to 5=most deprived) score of the area where the practice located, was also available as an extra explanatory variable to the patient data from practices in England. The IMD score is an UK government's official measure. [11] It is a composite score derived from seven domains: income, employment, health and disability, education skills and training, barriers to housing and services, crime and disorder, and living environment.

Statistical analysis
Data were described using count and percentage for categorical variables and mean (standard deviation, SD) for continuous data where applicable. Temporal patterns of service use (consultation, prescribing and referral) in the last 12 months of life were explored using the line chart by plotting month to death against the following statistics: 1) the proportion of patients using a specific type of service with a pre-defined intensity; 2) mean number of a specific type of service. The service use pattern was explored by the status of having palliative care needs recognised or not.
To facilitate interpretations of the findings and the comparability with other studies, we categorised all continuous variables. The generalised estimating equation (GEE) was used to account for the clustering effect within the practice, meaning that the patients from the same practice tended to have similar server use patterns. Three GEE regression models were constructed to evaluate variables independently associated with the outcomes. The

Socio-demographic and clinical characteristics of the study sample
68,735 patients meeting the inclusion criteria were extracted from the CPRD database.
After exclusion of 212 patients with ambiguous date of diagnostic information, the final study sample comprised of 68,523 patients. 71% of the patients were aged 70 years or above and 45% were women (Table 1). Lung cancer comprised over one third of the study sample, followed by colorectal cancer (24.2%) and roughly equal number of breast and prostate cancer. 75.1% of the patients had one or more comorbid conditions. Among all patients, 29.4% survived less than 6 months from their cancer diagnosis and 4.3% survived longer than 10 years. The study participants were dominated by the patients died in recent periods (2005-2014, 75.3%). Relatively more patients were from affluent regions (27.7% IMD1/2 vs 21.9% IMD 4/5). The study sample primarily comprised patients from practices in England (77.5%), followed by Scotland (10.3%), Wales (8.6%) and Northern Ireland (3.2%).

Patients' characteristics by status of palliative care needs recognised
Nearly half of the patients (45.5%) were identified as having palliative care needs.
Patients in the PC group died relatively young -35% died before the age of 70 compared to 24% in non-PC group. There were more lung cancer patients in PC than in non-PC group commonly prescribed drug groups were opioid analgesics (6.4%), proton pump inhibitors (4.5%), Non-opioid and compound analgesics (4.0%), antiplatelet drugs (3.9%) and Statins (3.1%). In the last 12 months, the proportion of patients receiving 10 or more monthly prescriptions from their GPs reached a peak (36.6%) in the penultimate month before death, then fell to the lowest level (15.4%) in the last month. Over the last 12 months, the GP prescribing rate was consistently higher in the PC group than in non-PC group ( Figure   2).

GP referrals
58% of the study participants had at least one referral in the last year (total N= 89,975).
The referral rate showed a slight increasing trend along with the closeness to death but remained at a lower level (7.0 to 11.8%) and dropped to the lowest (5.0%) in the month before death (Figure 3). The average number of referral specialities fluctuated in a small range (1.2 to 1.3). Patients in PC group had a slightly higher percentage with at least one end-of-life referral record and a higher average number of referring specialities than those in the non-PC group. Even with between 31 and 45% missing or non-specific specialty data, the referred specialities were broad and spanned two third (60 to 67) of the 93 listed specialties. The commonly referred specialties were general surgery or general medicine most of the time in the last year of life, and only in the last month palliative medicine became the second most referred specialty.

Factors associated with GP service use and PC status GP service use
The magnitude of association between patient characteristics and service use as measured by the adjusted risk ratio (aRR) was shown in Table 2 Patients with prostate cancer received more consultations, more prescriptions and a higher chance of referral than patients with any other cancers (aRRs 1.14 to 1.21).
Compared to lung cancer, colorectal cancer received more prescriptions and a higher chance of being referred (aRRs 1.04-1.05. Comorbidity was positively associated with consultations, prescriptions and referrals (aRRs 1.07 to 2.03), all with a dose-response relationship (p for trend <0.0001).
Patients who survived less than 5 years since their cancer diagnosis received more GP consultations (aRRs 1.05 to 1.31) than those who survived more than 5 years. However, only those who survived in between 6 and 36 months had more prescriptions (aRRs 1.05-1.07) than those who survived less than 6 months or longer than 3 years. Patients with a shorter survival (<1 year) had a higher chance of being referred to other specialities

Palliative care needs recognised
Older age (≥60 years), male gender and cancers of colorectal, prostate or breast were associated with a lower chance of having palliative care needs recognised. There was a dose-response relationship between age at death and the chance of PC group membership -aRRs ranging from 0.53 in 90+ to 0.89 in 60-69 age group. Patients with comorbidities were more likely to be in the PC group (aRRs 1.07 to 1.08). Patients who survived their cancer between 6 and 60 months had the highest chance of being in the PC group (aRRs 1.32 to 1.41), followed by those who survived less than 6 months or 5 to 10 years (aRRs

Sensitivity analyses
Sensitivity analyses (Appendix Tables 1-4) demonstrated similar results. Patients living in the deprived areas were less likely to having palliative care needs recognised and they also received less prescriptions from their GPs. There was no statistically significant difference in the number of consultations or referrals by social economic status.

Main findings and implications
In this large and nationally representative, retrospective cohort study, we found that most cancer patients managed by GPs have complex care needs [12], i.e. ≥70 years and with comorbidities. GPs maintain active contacts with terminal cancer patients towards the very end of their lives, though their involvement reaching a peak at the penultimate month before a sharp drop in the last month. GP consultations at the end of life rarely take place at a patient's home or their usual place of residence. Polypharmacy is common.
Patients over 70 years have fewer GP consultations but more prescriptions and a higher chance of referral to other specialities, suggesting their care needs may not be sufficiently met by primary care teams. Patients of prostate or colorectal cancer, with comorbidities, or with a shorter survival are high users of GP services. Having palliative care needs recognised increases the use of GP services, however, patients of old age have a significantly lower chance of use palliative care services.
Over the next several decades, it is anticipated that primary care teams will take more pressure to deliver care to those who are dying, as the patients with complex care needs will continue to rise and increasingly more people will die in the community settings. [13] Most people prefer to be cared for and die at home or in a home-like environment, should they have a choice. [14] Our data together with these projected trends and people's preferences highlight the importance to enhance provision of primary palliative care. As most cancer patients have one or more comorbidities, our data also challenge the singledisease oriented primary care system, particularly the appropriateness of the widely implemented 10 minutes' consultation model and some UK practices' policy of one problem per consultation.
The skill sets for primary palliative care include basic symptom management and psychological support, basic discussions about prognosis, treatment goals and advance care planning. [15] A previous study involving 513 GPs found that more than a quarter of the respondents reported receiving no or inadequate training in the delivery of end of life care. [16] A Danish study on GPs' self-reported competences in end of life care (n=573) found a similar proportion of the respondents don't feel confident about being a key care provider. [17] Another qualitative study concerning GPs' educational needs also reported a widespread lack of confidence in end of life care amongst both qualified and trainee GPs. [18] Our data support these findings and prompt actions to address the gaps in primary care providers.
A finding worth noting is the diverse needs of care among terminal cancer patients, as evident by a broad range of referral specialities throughout the last year of life. The primary care teams maintain active contacts with patients towards the very end of their lives, which offers opportunities for a greater integration of primary care with specialist palliative care, oncology, geriatrics and other healthcare specialities. In fact, the primary plus specialist palliative care has been proposed as a sustainable model to meet the high demand for palliative care. [15] Furthermore, GPs are well positioned and should play a key role to coordinate patients' care among multiple healthcare teams. [19] A system called Coordinate My Care, developed in the UK seeks to improve the communications among healthcare professionals and also patients' end of life care outcomes [20,21], though this and other approaches need robust evaluation.
Polypharmacy is common in our study population. In the 2 nd month of life GPs were still actively prescribing for patients, as high as 36% of the patient received 10 or more prescriptions from their GPs. A Swedish study using linked data covering all settings using the local cancer registry database linked to GP and hospital activity data found that access to and longer duration with palliative care were associated with better end-of-life quality indicators.
[32] Our data showed that palliative care was associated with the increased use of primary care services, but older people were less like to utilise palliative care services. This needs to be investigated further in future studies to inform the design of effective interventions to improve the situation.

Strengths and Limitations
This is the largest evaluation study of primary care service use at the end of life in cancer patients. Due to the strength of the database, we were able to track all the interactions between patients and primary care in the last year of life. However, we could not assess

Consent for publication
Not applicable.

Availability of data and material
According to the data agreement we signed with the data provider, we are not allowed to share our data. The access to the data would need special approvals from the CPRD office.

Competing interests
None declared.

Funding
The data access was granted under the MRC licence. This work is supported by the NCRI-      CPRD -appendix 1 QoF codes.txt