report of the exercise study - university of sheffield/file/...than men, younger than older, and...

University of Sheffield Medical Care Research Unit

University of Sheffield

A randomised controlled trial of the cost-effectiveness of exercise in over-65 year olds

James Munro Clinical Senior Lecturer

Jon Nicholl Professor

John Brazier Professor

Rachel Davey Research Associate

Tom Cochrane Senior Research Fellow

Correspondence to: James Munro Medical Care Research Unit University of Sheffield Regent Court 30 Regent St Sheffield S1 4DA. Tel: 0114 222 0759 Fax: 0114 222 0749 Email: [email protected]

Executive summary 20/05/02 Page 1


Contents

1. EXECUTIVE SUMMARY.......................................................................................4 1.1 Study design......................................................................................................4 1.2 Study outcomes.................................................................................................4 1.3 Participation in the programme .........................................................................4 1.4 Health effects of the programme.......................................................................4 1.5 Conclusions.......................................................................................................5

2. INTRODUCTION ...................................................................................................6

3. BACKGROUND RESEARCH...............................................................................7 3.1 Health benefits and risks of exercise ................................................................7 3.2 Health economics of exercise ...........................................................................8

4. METHODS.............................................................................................................9 4.1 Study aims.........................................................................................................9 4.2 Study overview ..................................................................................................9 4.3 Study populations..............................................................................................9 4.4 Intervention......................................................................................................10 4.5 Outcome measures and data collection..........................................................13 4.6 Statistical considerations.................................................................................15 4.7 Pilot study ........................................................................................................19 4.8 Safety ..............................................................................................................20 4.9 Ethical issues ..................................................................................................20

5. BASELINE COMPARISONS ..............................................................................21 5.1 Trial practices ..................................................................................................21 5.2 Inclusion and exclusion of trial subjects ..........................................................21 5.3 Characteristics of the study population at baseline.........................................24

6. PARTICIPATION.................................................................................................27 6.1 Classes offered ...............................................................................................27 6.2 Participation in the programme .......................................................................28 6.3 Other characteristics of “ever attenders” v “never attenders” .........................29 6.4 Adherence to the programme .........................................................................30

7. OUTCOMES: MORTALITY.................................................................................32 7.1 All cause mortality ...........................................................................................32



7.2 Mortality from selected causes........................................................................36 7.3 Cox regression of survival to selected causes of death..................................38

8. OUTCOMES: MORBIDITY .................................................................................40 8.1 Health status ...................................................................................................40

9. OUTCOMES: HEALTH SERVICE USE..............................................................53 9.1 Inpatient admissions........................................................................................53 9.2 Composite outcome: time to death or first admission .....................................57

10. ECONOMIC EVALUATION ............................................................................60 10.1 Approach .........................................................................................................60 10.2 Methods...........................................................................................................61 10.3 Analysis ...........................................................................................................62 10.4 Results.............................................................................................................63 10.5 Discussion .......................................................................................................65

11. DISCUSSION ..................................................................................................68 11.1 Summary of results .........................................................................................68 11.2 Are the results reliable?...................................................................................69 11.3 Pragmatic versus explanatory trials ................................................................70 11.4 Participation in the exercise programme.........................................................71 11.5 Conclusions.....................................................................................................72

12. ACKNOWLEDGEMENTS...............................................................................74

13. REFERENCES................................................................................................75



1. EXECUTIVE SUMMARY

This report describes the conduct and results of a pragmatic randomised controlled trial of a

community-based exercise programme for older adults, which attempts to assess the cost-

effectiveness of exercise, as an intervention, in a similar way to other health care interventions.

1.1 Study design

The subjects of the trial were the populations of 12 general practices in Sheffield, of which four

were randomly selected as intervention populations, and eight as control populations. In each

intervention population the least active four-fifths of those aged 65 and over were invited to

attend free supervised exercise sessions in local community settings. A variety of kinds of

exercise was provided in each area, including exercise to music, swimming, walking, bowling, Tai

Chi and dance, and eligible individuals were encouraged to attend whichever they chose. The

programme was provided for a two year period.

1.2 Study outcomes

The major study outcomes were all-cause and exercise-related mortality, health service use, and

health status. Mortality and health service use were assessed using routine NHS data. Health

status was assessed by means of postal survey at baseline, 12 and 24 months using the SF-36

instrument. In addition an economic evaluation was undertaken of the cost-utility of the

programme using a preference-based single index of health status derived from the SF-36.

1.3 Participation in the programme

During the two year period over 2,000 sessions of exercise were provided. In all, 26% of the

eligible study population attended one or more sessions. Attendance was greater among women

than men, younger than older, and most active than least active individuals. Of those ever

participating in the programme, 50% attended at least 28 sessions and 30% attended at least 60

sessions during the intervention period.

1.4 Health effects of the programme

There were no significant differences in all-cause mortality rates or survival times between

intervention and control practices. Restricting attention to death due to conditions which might be

prevented or delayed by exercise, there was no evidence of a difference in survival times

between trial arms, but a suggestion of lower mortality rates in intervention practices than in

control practices by 36 months. However, this did not reach statistical significance.

Health status was assessed in terms of the eight standard dimensions of the SF-36, together

with an “extended physical function” dimension, and three composite scores: the physical

component score (PCS), mental component score (MCS) and the preference-based single health

index. The decline in health status over the two year period appeared to be broadly similar in

intervention and control practices. After adjusting for baseline characteristics, patients in



intervention practices tended to have less decline in health status than those in control practices,

although this reached significance only for the energy dimension. The composite scores also

showed a tendency to less decline in health status over the two year period in intervention than

control populations. Examining changes only in the upper 90th centile of the outcome distribution

for changes in MCS, PCS and single health index showed similar results. Taken together, the

analysis of health status outcomes provided evidence of a small beneficial effect on the health of

the intervention populations.

The effect on inpatient admissions was examined both in terms of crude admission risk and time

to first admission. In addition, the composite outcome of time to first admission or death was

examined. In each analysis, we found no significant effect of the exercise programme on

inpatient admissions at the population level.

The economic analysis suggested that the exercise programme we provided would cost in the

region of £70,000 per year, with the average sessional cost per attender being in the region of

£5. There was a small average QALY gain, derived from the preference-based single health

index, of 0.010 for individuals in the intervention populations, compared with controls. However,

applying this across the whole of the intervention population gave a central estimate of cost per

QALY of £9,807. This figure compares well with the costs of other health care interventions, and

even under more pessimistic cost assumptions and a more conservative application of benefits,

the cost per QALY remained reasonable.

1.5 Conclusions

The trial raises a number of interesting and important methodological and policy issues. The

study was difficult to conduct, requiring a sustained intervention to be delivered to a large number

of people over a two year period, while at the same time evaluating its effects. The complexities

of the ethics, design, implementation and analysis of cluster-randomised trials have only begun

to emerge in the literature since this trial began, yet future pragmatic evaluations of the

effectiveness of health promoting interventions at community level will often have a similar design

and will have to consider similar difficulties with study power, the effects of low participation

across populations, and the difficulties of dealing with missing data when repeated outcomes

must be measured by postal surveys.

The programme we provided and evaluated generated both worthwhile changes in health-related

quality of life for the substantial number of regularly active participants, constantly remarked upon

and appreciated by the participants themselves, as well as an affordable average health gain at

the population level. A community-based intervention of this sort is practical, affordable,

enjoyable for participants and, our evidence suggests, justifiable in terms of health gain. The

economic evaluation also provides some further support for the contention that exercise is a

“best buy” in public health terms.



2. INTRODUCTION

There is considerable evidence to suggest that those with active lifestyles enjoy better physical

and mental health than sedentary individuals.1 2 There is also accumulating evidence that this

improved level of health is associated with lower health care costs.

Nicholl et al reviewed the costs and benefits of regular physical activity. They concluded that for

persons over 45 taking regular physical exercise there are clear net benefits in terms of improved

health and reduced health care costs.2 The main benefit is a reduced risk of vascular diseases,

principally coronary heart disease (CHD) and stroke. The results of the review also implied

substantial possible reductions in health service resource costs for the over 65s, assuming

exercise is as effective in this age group as it is in the over 45s.

That review did not, however, consider the costs involved in developing exercise programmes.

Subsequently, an economic model based on the findings of the review was developed in order to

estimate the possible costs and consequences of a community based exercise programme.3

Only reductions in those critical health events which typically would result either in hospital

admission or death were included. Potential health gain was measured in terms of lives

extended, life years saved, and reduced admissions. The direct costs of the proposed

intervention, such as exercise supervisors and the hire of exercise facilities, were included as

well as the resource consequences for the NHS of reduced admissions. The results were

sensitive to changes in assumptions about the reduction in incidence brought about by the

exercise programme, the cost of the programme, and life expectancy for persons over 65.

However, under a range of possible assumptions all cost per life year saved estimates were

between £100 and £1500. These figures compare very favourably with published cost per QALY

estimates.4

These are theoretical gains and the authors of the economic analysis recognised that the major

source of uncertainty in their model was the unknown effectiveness of any possible exercise

intervention occurring late in life. While estimates of effectiveness used in the model were based

on risk reductions found in observational studies, the benefits which result from an active lifestyle

which may have been life-long may not be reproducible in an exercise programme which is

relatively short-lived and occurs late in life. Furthermore, the practical benefits of such exercise

programmes, from a public health perspective, depend not only on the benefits of exercise itself

but also on uptake and compliance.

In view of this uncertainty, the current trial was proposed in order to determine the cost-

effectiveness of a community-based exercise programme for older people in preventing CHD,

stroke and other diseases.

Introduction 20/05/02 Page 6


3. BACKGROUND RESEARCH

3.1 Health benefits and risks of exercise

There is convincing evidence of the protective effect of exercise on the risk of CHD, at least in

men.5 6 A study estimating the risk of primary cardiac arrest reported that although the risk

increases transiently during vigorous activity, the overall risk in the physically active was 40% of

that in sedentary men.7 A follow-up study of the incidence of CHD amongst 17,944 male civil

servants demonstrated that participation in vigorous exercise reduced the risk for fatal and non-

fatal events by 40% and 50% respectively.8

The contribution exercise may have in reducing the incidence of stroke can be estimated directly,

or indirectly from its attenuating effect on blood pressure. A person's usual diastolic blood

pressure (DBP) is strongly and positively related to the risk of stroke not only in individuals who

are hypertensive but also in those who are normotensive.9 One randomised controlled trial in

persons aged 60-85 showed that exercise reduced usual DBP by an average of 5.0 mm Hg,10

and larger reductions have been found in other studies. After correction for bias, a meta-analysis

has estimated that there is a 34-56% reduction in the risk of stroke associated with a 5-10 mm

Hg reduction in usual DBP.9 In very close agreement with these indirect estimates, two direct

estimates found a relative risk of stroke between 41% and 20% lower in people undertaking

moderate exercise compared to those taking little or no exercise.11 12

CHD and stroke are not the only diseases which may be prevented by physical activity. There is

evidence of a reduction of between 43% and 86% in hip fracture risk in persons taking up

exercise,13 14 and a recent review concluded that regular physical activity is the single most

important intervention for the prevention of osteoporosis and hip fracture.15

There is also evidence that regular physical exercise may prevent late onset or non-insulin

dependent diabetes mellitus (NIDDM) with a relative risk of 0.71 in regular exercisers compared

to non-exercisers,16 as well as mild to moderate depression.17 In addition, exercise encourages

people to moderate other risk taking behaviour,18 19 reduces all-cause mortality,5 and also makes

people "feel better".20

Even though most of the primary research into the benefits of exercise has been conducted

among middle-aged adults, there is no particular reason to suggest that similar benefits would

not be found in older adults. Indeed, since most of the diseases which are clearly associated with

sedentary lifestyles are diseases of old age, it is in this group that the greatest benefits of

exercise might be expected. A recent review of the evidence for benefit in older adults, aged 65

and over, concluded that available data supported the conclusion that exercise would improve

cardio-vascular status, functional ability, mental functioning, and reduce fracture risk.21 This

review also noted that one remarkable aspect of research on exercise in older adults has been

the virtual absence of reports of serious cardio-vascular or musculo-skeletal complications in any

published trials.

Background research 20/05/02 Page 7


3.2 Health economics of exercise

Although it is clear that there may be benefits to health from exercise in older adults we do not

know how great these benefits might be nor the costs of achieving them. Nor is it clear whether

or not significant public health benefits can be achieved, as opposed to benefits simply for few

individuals at high risk.

The extent of the population benefit achievable will depend upon many factors, but levels of

compliance with the exercise programme will be most important. With regard to participation, US

studies have suggested that agreement to participate in exercise programmes is low. For

example, in two recent studies of exercise in persons aged 50-65, and 65 and over, after

excluding persons ineligible on medical grounds or who already exercised, only 44% and 20%

agreed to participate.22 23 However, in the latter study patients were asked to participate in a

randomised trial which could have involved high-intensity group exercise sessions, and this may

have discouraged participation. In contrast to these low participation rates, adherence rates have

been shown to be very good among people who are motivated to participate. In one British study

of a group of 87 healthy volunteers aged 60-81 years, 83% of all stipulated exercise sessions

were adhered to over an 8 month period.24

Background research 20/05/02 Page 8


4. METHODS

4.1 Study aims

The overall aim of the study was to quantify the cost-effectiveness of inviting a population of older

adults to a community-based programme of exercise, whether or not the invitation was taken up,

as an intervention to prevent or delay illness due to CHD, stroke, diabetes, mental illness or hip

fracture, and to promote health and well-being.

The specific objectives of the study were:

• to assess older adults’ participation and adherence to a free and locally available exercise

programme;

• to evaluate the effect of such a programme on individual and population physical activity,

quality of life, mortality, and use of health care;

• to estimate the cost-effectiveness of the programme, if it proves to result in health gains.

4.2 Study overview

The study was designed as a community intervention trial with randomisation of populations to

intervention or control arms. The units of randomisation were general practice populations, the

intervention was invitation to a community-based programme of regular, free exercise classes,

and the major outcome measures were mortality, health service use and health related quality of

life.

Twelve general practice populations were assigned randomly to the intervention (4 practices) or

control (8 practices) arm of the trial. This imbalance in intervention and control practices was

chosen because of the relatively small cost of including controls and the high cost of providing

exercise classes to intervention practices. Sedentary individuals aged 65 and over in the

intervention areas were invited to attend exercise classes (free to participants) provided near to

their homes. The programme of classes included a range of physical activities and ran for two

years.

Outcomes were measured in two principal ways. Habitual physical activity and health-related

quality of life were determined using a postal survey, at baseline and in two follow-up years.

Mortality and health service use were determined by reference to the NHS Central Register

(mortality) and to local health authority statistics (inpatient stays, outpatient and A&E

attendances).

4.3 Study populations

4.3.1 Recruitment of general practices

Twelve general practices in Sheffield were recruited to the study. Practices were selected at

Methods 20/05/02 Page 9


random from those practices with 2 to 5 partners which were not already known to be running an

exercise programme, exercise prescription scheme or related activity. Of 13 practices

approached, 12 agreed to participate. None of the practices was immediately adjacent to any

other in the study, in order to avoid the possibilities of contamination.

4.3.2 Randomisation of practices

Of the 12 participating practices, four were selected at random to act as intervention practices,

with the remaining 8 acting as controls. Randomisation was carried out using a computer random

number generator.

4.3.3 Definition of study cohorts

All individuals aged 65 or over on practice lists (both intervention and control) were sent a

baseline postal questionnaire to ascertain their general health status (using the SF-36) and

current levels of habitual physical activity (using the Physical Activity Questionnaire for the

Elderly).25 The responses to the physical activity questionnaire were scored according to the

published method, to produce an overall physical activity score for each individual.

From the population of survey respondents, those with an activity score in the top 20% of ranked

scores were excluded from the study, on the basis that these individuals were likely already to

have a lifestyle which was sufficiently active for the maintenance of good health. The figure of

20% is derived from the findings of the Allied Dunbar physical activity survey, which found that

approximately 20% of those over 65 are taking recommended levels of exercise.26 Thus, the

least active 80% of respondents in both intervention and control practices remained in the study.

The inclusion and exclusion criteria can be summarised as follows:

Inclusion criteria Exclusion criteria

Resident in Sheffield Physical activity score in top 20% of respondents

Currently registered with one of the participating study practices Identified as unsuitable for an exercise programme by their GP

Aged 65 or older Registered with intervention practices but living in a household

or institution in which some residents are in non-intervention

practices

Responded to baseline survey Living in an institution in which fewer than half of the residents

are registered in an intervention practice

4.4 Intervention

4.4.1 Nature of the intervention

The intervention was defined pragmatically as invitation to a locally organised, free and regular

programme of exercise classes. The mode of invitation is discussed below.



Exercise classes were provided in each of the areas served by the intervention practices. Each

class was arranged to run weekly, at the same time and place each week, and usually led by the

same exercise leader. In any week there would typically be four or five different classes

available, run from two or three venues, and participants were encouraged to aim to attend at

least two classes per week. Most classes were held in church halls, community centres and less

frequently in residential homes.

The Sport and Exercise Science Unit at the University of Sheffield has extensive experience in

designing structured exercise sessions which are acceptable and appropriate to older people.

Classes included activities aimed at improving joint mobility, muscle strength and endurance,

flexibility, balance and co-ordination and cardio-respiratory fitness. Strength training was carried

out using resistance bands (Therabands), with the number of repetitions increasing according to

the progress of the individual.

These activities were led by a qualified exercise leader and typically performed to music. Each

session had a slow warm-up with plenty of gentle stretch and mobility in order to minimise the

risk of injury, followed by a more vigorous middle section focussed on aerobic endurance and

strength conditioning, and a cool down section at the end. Time for meeting and talking with

friends over tea and biscuits was incorporated into the class schedule, and there would be an

option five to ten minute relaxation period at the end of the class. Most classes would last for

about 75 minutes, of which about 45 minutes would be physical activity.

These local sessions mainly focusing on aerobic activity formed the core of the programme

offered to study participants in the intervention areas. However, a range of other activities were

also organised to try to appeal to a broader range of people of different physical abilities and

different interests.

A gentle mobility class was offered to those who were interested in participating but were too frail

or disabled to take part in the main exercise classes. Minibus transport (in a vehicle adapted for

those with limited mobility) was provided for this class, and since this was expensive this class

could not be provided as frequently as the regular classes.

Weekly swimming sessions were organised, led by a qualified swimming instructor who was

experienced with older people. Again, because of the additional costs this class could not be

provided as frequently as the regular classes. Participants were asked to contribute a nominal

sum (50p each) towards the cost of hiring the pool.

To try to appeal to men, Crown Green bowling and indoor bowling sessions were offered. A tai

chi class was also successfully run. There were occasional tea dances and some groups also

arranged outdoor rambles when the weather was fine.

4.4.1.1 Home exercise

It was originally intended that those who preferred to exercise at home would be visited by a

qualified instructor and prescribed a range of suitable activities, and that subsequent



encouragement and support would be offered through home visits and telephone contact by the

instructor. However, in practice, this mode of exercise proved to be of little interest to study

participants. Those invited to exercise were either reluctant to become involved at all, or wanted

to attend group classes, since this offered the possibility of getting out and meeting people. Very

few were interested in exercising while staying at home. The support required from exercise

instructors to do this was time consuming and the instructors themselves were reluctant to invest

much time and energy in supporting a few individuals at home. This proposed element of the

programme did not therefore materialise in the way envisaged.

4.4.2 Expected participation and adherence

A number of US studies and at least one UK study provided some evidence in advance of this

study on expected levels of participation in exercise programmes among older people, though

none of the populations in published research was strictly comparable with that proposed in the

Sheffield study. In two US studies, 56% and 77% of those offered an exercise programme

refused to participate from the outset.22 23 Once subjects enter a programme, however,

subsequent adherence may be higher. A British study achieved an average 83% attendance at

sessions over an 8 month period.24 In one of the US studies of home and group based exercise,

75% of home exercisers and 53% of group exercisers were still exercising at 12 months.23 In the

American National Exercise and Heart Disease Project, in which the study population was men

aged 30 to 65 who had suffered a myocardial infarction in the previous 3 years, adherence at 3

months was 90%, only falling below 50% after 18 months.27

Barriers to participation mentioned by elderly people include boredom with the programme,

unawareness of how to get started, lack of self-discipline, unawareness of community

opportunities, transportation problems, and medical concerns.22

In proposing the current study, we argued that levels of participation similar to or better than

those observed in the US studies could be achieved. We argued that, for a retirement age

population, a number of factors might boost participation:

• the choice of day-time exercise sessions organised locally;

• initial contact with study participants would be made through the practice;

• GPs in intervention practices would encourage compliance through recommending the

exercise programme to their elderly patients;

• exercise twice weekly would be required of participants, as opposed to three times weekly in

the US studies cited;

• individuals who decline group-based sessions would be offered home exercise with regular

telephone and in person support.

In the sample size calculations below, therefore, we assumed an initial refusal rate of 40%, and



an adherence rate of 70% at 24 months.

4.4.3 Recruitment of participants

Following the initial postal survey to practice populations, an invitation letter was sent to the least

active 80% of respondents (as described above). The letter was sent from the research team and

invited respondents to indicate an interest in attending local exercise sessions twice weekly.

Once a timetable was arranged in each area a further letter was sent to respondents with more

information and inviting them to the first session.

Subsequently, three further letters were sent to all eligible exercise participants in each of the

intervention areas: a Spring newsletter and an invitation letter, about 6 months later; an invitation

to a summer fete and dance, about 10 months later; and an Autumn newsletter and invitation

letter, about 14 months later. In addition, news of specific activities was sent to respondents who

had indicated an interest in these.

4.4.4 Measurement of participation and adherence

At all classes and events provided in the context of the study, attendance rolls were taken by the

exercise facilitator. Thus, every attendance by each study participant was logged into the study

database for later analysis.

4.5 Outcome measures and data collection

4.5.1 Mortality

The deaths of study participants were identified in 3 ways:

a) the practice managers of participating general practices were periodically asked to provide a

list of all patients over 65 who had died, with the date of death;

b) the local health authority population register was queried to identify the date of death of any

study subjects;

c) study subjects who did not reply to the final annual survey were flagged with the NHS Central

Register in Southport, who supply a copy of the death certificate in the case of a death, giving

date and cause of death.

4.5.2 NHS use

4.5.2.1 Inpatient admissions, outpatient attendances and A&E visits

Each patient record provided by participating practices was matched to Sheffield Health

Authority’s patient register. For contracting purposes, the health authority maintains a record of

all inpatient admissions, outpatient attendances and A&E visits by Sheffield residents. This

database was queried at the start of the trial, and periodically throughout the trial period, to



identify all such use of health services by study participants during the two years prior to, and two

years following, the start of the trial.

4.5.2.2 GP contacts

The baseline postal survey sent to study subjects included two questions asking about contact

with the general practitioner:

• have you been to see your doctor during the past two weeks?

• has your doctor been to see you during the past two weeks?

These questions reflect those used in the General Household Survey, and were repeated in each

of the two subsequent follow up surveys.

4.5.3 Social care

Two approaches were taken to identifying the use of various social care services by study

participants. First, questions on the use of nursing or residential care, home care, meals on

wheels and day care were included in the two follow up postal surveys.

Second, attempts were made to make use of routine data on social care collected by Sheffield

City Council. Early in the study period the council computerised its records of all Sheffield

residents receiving any social care paid for by the council. Access to these records was

negotiated and records matching our study cohort were obtained. Unfortunately, the quality and

completeness of the data proved to be poor, and the data included many duplicate records the

validity of which could not be determined. Given these problems, we felt unable to include this

data source in the study.

4.5.4 SF-36

Many of the benefits of exercise may extend beyond life threatening critical events such as heart

attacks and strokes, to include more general effects on “quality of life” outcomes such as energy,

vitality or feelings of well-being. Health-related quality of life, measured using the well-established

SF-36 instrument, was therefore included as a study outcome. This instrument generates scores

on eight dimensions (physical functioning, mental health, social function, pain, physical and

emotional role limitations, vitality and general health). It has been used successfully in the UK on

a general population up to the age of 75,28 although concerns have been expressed about low

completion rates in those aged 75 and over.29 However, it has been used by its developers in the

US on a population over 75, and found to achieve satisfactory levels of completion and

reliability.30

The SF-36 was included in the baseline and two subsequent postal surveys to study participants.

Three minor changes were made to the standard question layout in view of the fact that the

respondent population was retired and potentially in poor health. First, the order of items in



question 3 (typical daily activities) was reversed so that instead of moving from most vigorous to

least vigorous activity, the question began with the least vigorous. Second, three additional

activities were added to this question to accommodate the possibility that some respondents may

not be capable of even the most limited activity in the standard list (i.e. bathing or dressing

yourself). The three activities added were:

• feeding yourself

• getting up from a chair

• walking in your home

In this way we hoped to lower the “floor” for the Physical dimension of the instrument so that it is

more sensitive to change in those who are severely limited. To allow our results to be compared

with those using the usual questions, however, we report both the standard Physical dimension

and our “extended Physical dimension” in the results.

Third, we altered the wording of questions 4 and 5 to remove the phrase “work or other”, since

this would not be applicable to a retired population.31

4.5.5 Physical activity

The habitual physical activity of study participants was measured using a questionnaire

specifically developed for older adults.25 The physical activity questionnaire (PAQ) is made up of

two sections: the first includes 10 questions on everyday household activities; the second allows

respondents to report on leisure time physical activities or hobbies, and asks about the time

spent on these. Responses to these questions are then combined into a score using the

published weightings.

4.6 Statistical considerations

4.6.1 Sample sizes

The principal outcomes in the trial are the incidence of death or admission resulting from CHD,

stroke, hip fracture, NIDDM, and mental disorders, and the costs of these events; as well as self-

reported health-related quality of life.

Approximately 7.5% of the general population over 65 are admitted or die from these selected

causes each year. The study excludes 20% of the elderly population because they are already

exercising to a sufficient degree.26 These relatively healthy people may have a 50% lower risk of

the target conditions. Similarly, it was expected that up to 15% of the group would be excluded by

their GPs as being unsuitable for exercise prescription on medical, social, or other grounds.22 23 24 This relatively unhealthy group may have a risk twice that in the remaining group. The net

effect of these exclusions was that the expected two year incidence of these conditions in the

population aged over 65 who would be offered exercise was 14%.



In order to have an 80% change of detecting as significant (at p


covariates have been included, and also a practice level covariate (the practice's Townsend

deprivation score). The MLM has been used to test for differences between the proportions of

the intervention and control practice samples who had died by two years.

4.6.2.2 Cause specific mortality

A literature review identified five causes for which there is good evidence that exercise is

associated with a reduction in mortality. All the mortality analyses described above have been

repeated for deaths only from these causes. Deaths from other causes have been treated as

censored survival times for the Cox regression. For the comparison of crude rates, deaths from

other causes have contributed person-months of observation to the denominators. For the

MLMs comparing proportions of deaths at two years, the persons dying from other causes have

been deleted (as missing values whose outcomes were not known).

4.6.2.3 Hospital admissions

Crude all cause admission risk (the proportion of all survivors in the sample admitted to hospital

for any reason at any time during the two years from the start of the study) have been calculated

for each intervention and control practice. These crude proportions have been compared using a

simple Mann-Whitney rank test. For these analyses persons who died within two years have

been omitted since their outcome (admitted within two years) was not known.

These admission proportions have also been compared using multi-level random effects models,

adjusting for person-level and practice-level covariates, as for mortality. In addition, a baseline

measure indicating whether or not the patient had been admitted in the two years prior to the

study starting has also been included as a covariate in these models.

4.6.2.4 Composite outcomes

Time to death or first admission has also been calculated for each person in the study and

compared between intervention and control practice populations. The crude proportion of

subjects suffering this composite outcome has been calculated for each practice and compared

between intervention and control practices.

Cox regression adjusting for personal characteristics has been used to obtain a set of practice

effects, which have then been compared using a simple rank test on the size of the estimated

effects. This composite outcome analysis has been repeated for time to first admission or death

from any of the five specified causes.

4.6.2.5 Other health service use

The baseline, 1 year, and 2 year follow-up questionnaires asked the patients in the study

whether they had seen their GP in the previous two weeks.

The proportions of patients in the intervention and control practices who had seen their GP in the

previous two weeks have been compared at both 1 year and 2 years. Crude unadjusted



estimates have been compared, and also proportions adjusted for personal characteristics

(including the baseline measure) and practice level characteristics, using multi-level random

effects models.

4.6.2.6 General health scores

General health status was measured using the SF-36, and the scores for the eight dimensions of

the SF-36 and our additional ‘extended physical function’ dimension have been calculated.

These dimension scores have also been combined into three composite scores: the physical

component score (PCS), the mental component score (MCS), and a preference-based single

index of health. 33 34 Comparisons of summary measures of all nine dimensions and the three

composite scores have been made. The summary measures used were the means and 90th

centiles of the area under the 'curve' defined by the scores at baseline, 1 year, and 2 years, net

of the baseline score. These areas represent the gain or loss in health over the two years of the

study and are analogous to quality of life years gained (see Figure 4-1 below).

Figure 4-1: Example of area under curve calculation

0

20

40

60

80

100

Baseline 1 year 2 years

Health loss over 2 years

Comparisons adjusted for the covariates were made using fixed effects randomisation tests and

random effects multi-level models. In these analyses the baseline score has also been used as a

covariate in the adjusted comparisons.

4.6.2.7 Sub group analyses

Many eligible people in the intervention practice samples did not take any additional exercise

through the programme of 'interventions' offered. Some people took a little, attending one or a



few exercise sessions, while others participated fully, attending hundreds of exercise sessions

during the two year study period. It would, of course, be extremely helpful to understand whether

the results of the study are due to the effects of exercise, or due to these levels of compliance. It

is therefore natural to attempt to examine results in sub-groups of the intervention sample,

defined by their level of compliance with the exercise offered. However, people have selected

themselves into these sub-groups in two distinct ways.

First, people with different characteristics have responded to our invitation to take exercise either

by coming along on at least one occasion or not coming at all. Second, among those who have

come along some have stayed with exercise and some have dropped out. It is important to

understand the fundamental difference between these two types of 'selection' processes. The

first type can be adjusted for – at least in principle. The second can not.

The first type of selection is due to people having different (baseline) characteristics. These may

be economic, social, physical, psychological and so on, but in principle they are measurable

baseline characteristics which could be used to compare like with like between groups of people

who volunteered to participate and those who did not.

However, among those who started exercise those who stayed with it, and those who dropped

out, represent groups not selected by baseline characteristics, but selected at least in part by

outcome. Participants who felt a benefit may have stayed on, while those who felt little or no

benefit or even sustained an injury or other perceived harm will have dropped out. These groups

have selected themselves by their outcomes, and clearly their outcomes cannot be compared.

We have therefore undertaken only one set of sub-group analyses comparing those who took

part in at least some exercise sessions with those who took part in none. We have adjusted

these comparisons for all the baseline characteristics which we have measured.

We recognise that the adjustment for the baseline characteristics we have measured can only

partially take into account selection effects, since there may be other unmeasured characteristics

which both helped determine participation and influenced outcome. One possible way around

this is to recognise that if only a small proportion of the intervention practice populations

participate (and therefore receive the intervention) only a small part of the outcome distribution

can have been affected. We should therefore expect that the outcome distribution will not have

been ‘shifted’, but rather changed in shape, possibly with a different and longer tail of good

outcomes. For this reason we have also compared the 90th centile of the outcome distributions of

the composite SF-36 scores, using simple re-randomisation tests, with the difference in the 90th

centiles as the “test statistic”.

4.7 Pilot study

A pilot intervention programme was run in a practice not included in the main trial, to allow the

organisational aspects and the compliance assumptions of the study to be tested. Patients over

65 on a single practice list were sent the baseline questionnaire and recruited to a ten week



exercise programme supervised by one of the principal researchers. The results of the pilot study

have been published elsewhere,35 and are reproduced as an appendix to this report.

4.8 Safety

The likelihood of significant adverse effects attributable to the exercise programme was

considered to be minimal. The published trials of exercise in the sedentary elderly suggest that

there are very few complications associated with increases in activity.21 Cardiac rehabilitation

programmes, which enrol many people over 65 with known coronary artery disease, report few

major cardiovascular complications.36 37

At recruitment, all participating practices were fully informed of the aims of the study and briefed

on the health benefits and risks of exercise in the elderly. Before the exercise programme was

offered to subjects in intervention practices, GPs were asked to exclude any patients for whom

they felt the exercise programme was unsuitable, for whatever reason.

Individuals who agreed to take part in the exercise programme were instructed at their first

session on how to begin exercising in a safe and effective way, what potential the health risks of

exercise might be, and asked to make slow but steady progress with their exercise programme.

Advice on symptoms to be aware of (such as chest pain, irregular pulse, dizziness and

breathlessness) and appropriate responses was also given. Known diabetics were informed of

the possible effects of exercise on their blood sugar control and were asked to bring a sugar

snack in any convenient form to their exercise sessions. Exercise session leaders had first-aid

training, including training in CPR.

4.9 Ethical issues

The approval of Sheffield Local Medical Committee and the local research ethics committees

was obtained. Informed written consent was obtained from all subjects taking part in the exercise

programme.



5. BASELINE COMPARISONS

5.1 Trial practices

Twelve Sheffield practices were recruited to the study according to the methods set out above.

The characteristics of these practices are shown in Table 5-1.

Table 5-1: Characteristics of study practices

Practice attributes Patient attributes

Practice Trial status Number of GPs (wte)

Mean age of GPs

List size Unemployed (%)

Townsend score

Jarman score

Limiting long term illness (%)

A Intervention 2.75 37.3 6385 7.16 0.782 7.85 16.6

B Intervention 5 37.0 8016 6.34 0.403 5.57 17

C Intervention 3 42.3 6252 7.45 0.819 8.23 17.1

D Intervention 2.5 40.3 5690 10.2 1.64 13.1 17.8

E Control 3 36.7 5385 6.25 -0.0478 3.14 17.6

F Control 2 52.0 4846 7.15 0.492 6.41 17

G Control 2.5 43.0 3125 9.88 0.852 7.04 16.8

H Control 4.5 43.4 8943 3 -2.18 -1.58 8.53

I Control 4 43.8 8212 4.75 -1.54 0.864 14.7

J Control 2 43.0 4862 4.53 -1.11 -2.4 15.5

K Control 3 38.0 5442 8.55 1.44 12 20.2

L Control 2 50.5 1969 9.67 0.484 4.15 15.5

5.2 Inclusion and exclusion of trial subjects

The baseline survey was sent to all patients on practice lists whose date of birth was earlier than

1 April 1930. Survey mailings began in April 1995, so that all subjects were aged 65 or over at

the start of the study. The numbers of subjects sent a survey and the response rates by practice

and overall are shown in Table 5-2.

Baseline comparisons 20/05/02 Page 21


Table 5-2: subjects aged 65 and over in 12 practice populations

Practice Status n mean age female (%) Responders Response rate

A Intervention 931 73.6 58.8 770 82.7%

B Intervention 894 75.6 62.2 672 75.2%

C Intervention 985 75.1 59.9 789 80.1%

D Intervention 886 76.0 64.9 663 74.8%

E Control 1177 74.3 60.1 1028 87.3%

F Control 952 75.5 56.3 778 81.7%

G Control 528 74.5 63.3 431 81.6%

H Control 657 75.0 25.7 593 90.3%

I Control 726 74.8 58.5 585 80.6%

J Control 807 75.1 58.1 703 87.1%

K Control 919 73.8 60.4 759 82.6%

L Control 435 75.8 60.0 346 79.5%

All 9897 74.9 57.8 8117 82.0%

Response rates after two reminders were reasonable, with an overall response rate of 82%. The

response rate fell below 80% in only three practices (two intervention and one control practice).

After the most active one-fifth of respondents were excluded from the study, 6420 subjects

remained. A flowchart summarising the derivation of this population in shown in Figure 5-1.



Figure 5-1: Study subjects: numbers included in the trial

subjects in control practices: 4137

died before 1/8/95:

29

most active one-fifth: 1612

missing activity score: 56

least active four-fifths:

6420

gone away: 126

died: 1

no response: 1461

refused: 192

completed surveys returned:

8117 (82%)

sent baseline survey:

9897

12 practice lists: all patients with dob before 1/4/1930

9897 subjects

subjects in intervention practices: 2283



5.3 Characteristics of the study population at baseline

5.3.1 Demographic characteristics

Table 5-3 shows various demographic characteristics of the populations included in the study, by

practice. These characteristics were derived from the practice list data provided by each practice,

and from responses to the postal survey.

Table 5-3: Demographic characteristics of study subjects at baseline

Practice Status n mean age female

(%)

Nursing/residential home residents

%

Owner-occupiers

%

Living alone

%

Smoker

%

A Intervention 609 74.3 65.0% 0.3% 29.2% 37.1% 22.3%

B Intervention 525 76.4 69.1% 7.6% 38.3% 41.3% 12.2%

C Intervention 622 75.7 65.3% 3.2% 25.2% 37.9% 16.2%

D Intervention 527 75.8 68.3% 3.4% 59.8% 43.1% 11.6%

E Control 810 74.8 66.2% 0.2% 41.1% 40.5% 15.7%

F Control 611 76.1 61.5% 0.0% 43.4% 46.2% 19.8%

G Control 339 75.6 68.1% 0.9% 20.6% 46.3% 23.9%

H Control 473 75.9 27.5% 2.1% 79.3% 30.4% 11.6%

I Control 462 75.5 62.6% 1.9% 17.7% 44.2% 21.0%

J Control 562 75.9 64.2% 0.7% 53.7% 40.0% 14.6%

K Control 605 74.1 64.5% 2.5% 18.0% 40.3% 22.6%

L Control 275 76.4 63.3% 5.5% 40.7% 42.5% 16.0%

All 6420 75.4 62.5% 2.1% 38.9% 40.6% 17.2%

5.3.2 Physical activity

The habitual physical activity scores of study subjects (who exclude the most active one-fifth)

measured at baseline are shown in Table 5-4.

Table 5-4: Mean habitual physical activity scores at baseline

Practice Status PAQ leisure PAQ household PAQ total

A Intervention 2.6 1.8 2.9

B Intervention 3.2 1.8 3.0

C Intervention 2.9 1.8 3.1



D Intervention 4.0 1.9 3.9

E Control 3.4 2.0 3.6

F Control 2.9 1.8 2.9

G Control 1.8 1.8 2.2

H Control 5.1 1.9 5.1

I Control 1.9 1.7 2.2

J Control 3.6 1.8 3.6

K Control 2.1 1.8 2.4

L Control 2.6 1.8 2.8

All 3.2 1.8 3.2

Figure 5-2: Mean total habitual physical activity score at baseline

0

1

2

3

4

5

6

H D E J C B A F L K G IPractice

Mean

phy

sical

activ

ity sc

ore

ControlIntervention

5.3.3 Health-related quality of life

Mean scores from the SF-36 domains at baseline, together with the extra domain “extended

physical functioning”, are shown in Table 5-5.



Table 5-5: Mean SF-36 scores at baseline

Practice Status Physical Social Role physical

Role emotional

Mental Vitality Pain GHP Extended physical

A Intervention 47.2 63.1 31.5 46.5 65.8 46.5 55.1 48.6 54.6

B Intervention 48.8 66.7 33.9 45.4 66.5 47.4 58.9 50.1 56.2

C Intervention 46.4 61.2 30.7 44.1 66.2 45.1 54.3 49.4 53.8

D Intervention 52.1 68.5 43.8 58.6 70.1 49.9 62.7 55.5 59.3

E Control 49.6 65.5 34.5 48.7 66.7 47.6 56.4 50.8 56.5

F Control 44.8 61.4 29.8 43.4 67.1 45.4 55.3 49.6 52.3

G Control 44.6 60.5 34.0 43.0 62.9 44.9 55.6 47.1 51.2

H Control 63.6 80.4 57.8 75.0 78.7 57.3 73.5 61.0 69.3

I Control 43.3 62.2 32.3 43.8 66.0 45.6 55.3 47.8 51.0

J Control 48.1 66.8 38.0 53.0 70.9 49.5 58.0 52.2 55.1

K Control 42.3 58.0 28.2 39.5 62.0 43.8 53.5 45.0 49.5

L Control 46.2 63.1 36.2 51.8 65.8 47.2 58.7 50.4 52.7

All 48.1 64.7 35.4 49.1 67.4 47.4 57.8 50.6 55.2



6. PARTICIPATION

6.1 Classes offered

Over two year intervention period, a total of 2 040 exercise classes of various kinds were

provided, resulting in a total of 27 800 person-sessions of exercise (an overall mean attendance

of almost 14 persons per class). The majority of classes lasted about 75 minutes, of which about

45 minutes would involve physical activity. The number of classes offered and the number of

study subjects attending, together with the mean number of attenders per class, are shown in

Table 6-1, by calendar quarter.

Table 6-1: Classes offered and attended during the intervention period

Calendar quarter 95-3 95-4 96-1 96-2 96-3 96-4 97-1 97-2 97-3 Total Classes offered Crown Green bowling 9 24 6 1 40 Dancing 2 5 7 20 11 4 6 2 57 Gentle mobility 5 26 41 72 69 75 54 342 Indoor bowls 4 12 5 9 5 11 46 Social event 1 1 2 Standard exercise class 25 133 181 176 190 140 184 134 2 1165 Swimming 15 37 50 52 55 48 46 303 Tai Chi 5 13 13 15 12 12 13 83 Walking 1 1 2 All classes 25 164 274 303 375 296 334 265 4 2040 Number of “person-classes” attended Crown Green bowling 52 133 70 15 270 Dancing 22 19 182 139 103 63 83 21 632 Gentle mobility 59 169 306 425 437 451 317 2164 Indoor bowls 25 64 25 130 76 129 449 Social event 30 142 172 Standard exercise class 613 3395 3204 3012 2937 2063 2621 1750 16 19611 Swimming 218 482 573 526 513 379 402 3093 Tai Chi 117 278 252 254 204 157 115 1377 Walking 15 17 32 All classes 613 3836 4216 4447 4573 3450 3817 2811 37 27800 Mean attendance per class Crown Green bowling 5.8 5.5 11.7 15.0 6.8 Dancing 11.0 3.8 26.0 7.0 9.4 15.8 13.8 10.5 11.1 Gentle mobility 11.8 6.5 7.5 5.9 6.3 6.0 5.9 6.3 Indoor bowls 6.3 5.3 5.0 14.4 15.2 11.7 9.8 Social event 30.0 142.0 86.0 Standard exercise class 24.5 25.5 17.7 17.1 15.5 14.7 14.2 13.1 8.0 16.8 Swimming 14.5 13.0 11.5 10.1 9.3 7.9 8.7 10.2 Tai Chi 23.4 21.4 19.4 16.9 17.0 13.1 8.8 16.6 Walking 15.0 17.0 16.0 All classes 24.5 23.4 15.4 14.7 12.2 11.7 11.4 10.6 9.3 13.6

Participation 20/05/02 Page 27


6.2 Participation in the programme

All 2 283 individuals in the intervention population were invited to attend exercise classes, by the

various means outlined above. Of these, 590 (26%) attended one or more sessions at some time

during the two year programme. The proportion of women attending at least one class

(436/1525, 29%) was significantly greater than the proportion of men attending (154/758, 20%)

(p


Figure 6-1: Proportion of subjects ever attending, by baseline total physical activity score

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

0 1 2 3 4 5 6 7 8 9 10+Baseline physical activity score

Prop

ortio

n ev

er at

tend

ing

Figure 6-2: Proportion of subjects ever attending, by baseline General Health Profile score

0%

5%

10%

15%

20%

25%

30%

35%

0: 9 10: 19 20: 29 30: 39 40: 49 50: 59 60: 69 70: 79 80: 89 90: 99 100:100Baseline GHP score

Prop

ortio

n ev

er at

tend

ing

6.3 Other characteristics of “ever attenders” v “never attenders”

Other characteristics which were found to be associated with participation were smoking status



and type of accommodation (Table 6-3). Living alone was not found to be associated with

participation, suggesting that it was characteristics of the individual rather than the social nature

of the exercise classes which affected whether the target participant ever attended.

When all the baseline characteristics (age, sex, smoking status, type of accommodation, living

along, total physical activity score, and SF-36 single index score) were entered into a multivariate

model together, age, sex, smoking status, type of accommodation, and baseline physical activity

score all had a strongly significant impact on participation.

Table 6-3: Characteristics of attenders

Characteristic Never attended

n

Ever attended

n

% ever attending p value

Smoking

Smoker 307 55 15.2 0.5

No 1011 343 25.3

Not known 19 4

Accommodation

1 38 42 52.5


Table 6-4: Number of classes attended by “ever attenders”

Number of classes attended Participants Proportion of “ever attenders”

5 or fewer 170 29%

6 to 20 86 15%

21 to 50 122 21%

51 to 100 123 21%

More than 100 89 15%

All “ever attenders” 590

Attendance data is also displayed graphically, in Figure 6-3 below, as the proportion of “ever

attenders” attending at least the number of sessions on the x axis. This shows that 50% of

participants attended at least 28 sessions, and 30% attended at least 60 sessions, at some time

in the study period.

Figure 6-3: Proportion of “ever attenders” attending at least a given number of sessions

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 50 100 150 200 250 300Number of sessions attended

Prop

ortio

n of

"ev

er a

ttend

ers"



7. OUTCOMES: MORTALITY

7.1 All cause mortality

In the first 24 months of the study 788 of the 6420 subjects had died (12.3%). The proportion was

similar in each cohort: 12.4% of the intervention cohort and 12.2% of the control cohort. By 36

months 990 individuals had died (15.4%), and again this proportion was the same in each cohort.

7.1.1 Crude death rates by practice

The crude death rates for each of the 12 practices at 24 and 36 months after the start of the

exercise programme are shown in Figure 7-1 and Figure 7-2, below.

Figure 7-1: Crude death rates per year by practice, at 24 months

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

80.00

90.00

B I J G H F C K A D L EPra ctic e

Deat

h ra

te p

er 1

000

subj

ects

per

yea

r

Interven tion prac tice

C ontrol prac tice

Outcomes: mortality 20/05/02 Page 32


Figure 7-2: Crude death rates per year by practice, at 36 months

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

I B L J F C G H K D A EPractice

Deat

h ra

te p

er 10

00 su

bjec

ts p

er ye

ar

Intervention practice

Control practice

Rank testing of the crude death rates by practice showed no significant difference between

intervention and control practices, as Table 7-1 shows.

Table 7-1: Rank testing of practice crude death rates

Mean rank of intervention

practices

Mean rank of control

practices

U statistic 2-sided p

Crude death rate at 24 months 6.25 6.63 15 0.93

Crude death rate at 36 months 5.75 6.88 13 0.68

7.1.2 Survival times: simple cluster analysis

The individual survival times of study subjects were also examined using Cox regression. Two

regression models were used. In the first, the individual’s practice was entered alone. Regression

coefficients from this model are shown as the “unadjusted exp(β)” in the table below. In the

second, the following potential confounders were also entered in the model: age, sex, whether

living alone, type of accommodation, whether a smoker, and baseline physical activity score. The

practice coefficients from this model are shown as the “adjusted exp(β)” in the table below and in

the bar chart which follows.

Table 7-2: Cox regression of survival time to any cause of death



Practice Status Unadjusted Exp(B) 95% CI Adjusted Exp(B) 95% CI

A Intervention 1 1

B Intervention 1.41 1.02-1.94 1.28 0.92-1.78

C Intervention 1.05 0.76-1.46 0.93 0.67-1.3

D Intervention 0.98 0.69-1.39 1.05 0.74-1.51

E Control 0.93 0.67-1.27 1.07 0.78-1.47

F Control 1.11 0.8-1.54 0.99 0.71-1.37

G Control 1.18 0.81-1.72 0.98 0.67-1.43

H Control 1.14 0.81-1.61 1.03 0.71-1.48

I Control 1.25 0.89-1.76 0.87 0.61-1.24

J Control 1.20 0.86-1.66 1.26 0.9-1.76

K Control 1.00 0.72-1.4 0.84 0.6-1.19

L Control 0.96 0.62-1.47 0.80 0.52-1.24

Figure 7-3: Cox regression of survival: adjusted exp(β) by practice

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

B J E D H A F G C I K L

Practice

Adj

uste

d Ex

p (B

)

Control

Intervention

Rank testing of the unadjusted and adjusted Cox regression coefficients by practice showed no

significant difference between intervention and control practices, as Table 7-3 indicates.

Table 7-3: Rank testing of practice Cox regression coefficients

Mean rank of intervention Mean rank of control U statistic 2-sided p



practices practices

Unadjusted coefficients 6.25 6.63 15 0.93

Adjusted coefficients 8.00 5.75 10 0.37

7.1.3 Survival times: nested split-plot models

The results shown above suggest that there is no significant difference between the mortality

rates or survival times of different practice populations. As an additional check on whether there

might be any overall effect of trial arm on mortality, over and above the practice-level effect, the

ability of three successive Cox regression models to explain variation in survival times was

examined, as follows:

• model A included likely confounders only

• model B included likely confounders, plus trial arm

• model C included likely confounders, trial arm and practice

The results of this analysis are shown in Table 7-4, and indicate that there is unlikely to be any

overall effect of trial arm on mortality. The survival curves for intervention and control cohorts are

shown in Figure 7-4.

Table 7-4: test for overall effect of trial arm on mortality

Model Model covariates -2 log likelihood of model

Model A Confounders only 12830.786

Model B A plus arm 12829.902

Model C B plus practice 12817.550

F1,11 statistic Calculated as (A-B)/(B-C)*10 0.716

(p>0.05)

Figure 7-4: Survival curves by arm



Trial armIntervention

Control

Survival curves by arm

Survival time (days)

8006004002000

Cum

ulat

ive s

urviv

al1.00

.80

.60

.40

.20

0.00

7.2 Mortality from selected causes

As argued above, there is evidence in the literature that at least five important conditions may be

delayed or prevented by regular exercise. We have therefore repeated the mortality analysis,

restricting attention solely to deaths coded as due to coronary heart disease, cerebrovascular

causes, mental illness, fractured neck of femur or diabetes.

In the first 24 months of the study 330 of the 6420 subjects had died from these selected

conditions (5.1%). The proportion was similar in each cohort: 4.7% of the intervention cohort and

5.4% of the control cohort. By 36 months 420 individuals had died of these conditions (6.5%),

being 6.0% of the intervention cohort and 6.9% of the control cohort.

7.2.1 Crude death rates for selected causes by practice

The crude death rates for these conditions for each of the 12 practices at 24 and 36 months after

the start of the exercise programme are shown in Figure 7-5 and Figure 7-6, below.



Figure 7-5: Crude death rate for selected causes, by practice, at 24 months

0.00

5.00

10.00

15.00

20.00

25.00

30.00

35.00

40.00

H F B J I G D K L C E APractice

Deat

h ra

te p

er 10

00 su

bjec

ts p

er ye

ar


Control practice

Figure 7-6: Crude death rate for selected causes, by practice, at 36 months

0.00

5.00

10.00

15.00

20.00

25.00

30.00

H I L F J D K B G C E APractice

Deat

h ra

te p

er 10

00 su

bjec

ts p

er ye

ar


Control practice

Rank testing of the crude death rates by practice showed no significant difference between

intervention and control practices (Table 7-5), although there was a suggestion of lower mortality

at 36 months for the selected causes in the intervention practices. This is reflected in the charts

above, and raises the question of whether longer follow-up might be worthwhile to detect



changes in mortality rates beyond the two year intervention and one year mortality follow up

period.

Table 7-5: Rank testing of practice crude death rates from selected causes


practices


practices


Crude death rate at 24 months 5 7.25 10 0.31

Crude death rate at 36 months 4 7.75 6 0.09

7.3 Cox regression of survival to selected causes of death

As before, survival times were examined using Cox regression. In this instance, only death due

to one of the five selected causes counted as an endpoint, while deaths from other causes were

censored. Again as above, the coefficients from a simple (“unadjusted “) Cox regression and

from a second (“adjusted “) model including the potential individual confounders are reported

below.

Table 7-6: Cox regression of survival times

Practice Status Unadjusted Exp(β) 95% CI Adjusted Exp(β) 95% CI

A Intervention 1 1

B Intervention 1.393 0.82-2.38 1.15 0.67-2

C Intervention 1.099 0.64-1.88 0.94 0.55-1.62

D Intervention 1.168 0.67-2.03 1.15 0.65-2.01

E Control 1.082 0.65-1.8 1.18 0.71-1.97

F Control 1.538 0.93-2.55 1.31 0.79-2.19

G Control 1.236 0.67-2.29 1.01 0.55-1.88

H Control 1.758 1.05-2.95 1.37 0.79-2.37

I Control 1.278 0.73-2.24 0.90 0.51-1.6

J Control 1.368 0.81-2.32 1.29 0.75-2.21

K Control 1.161 0.68-1.98 1.02 0.59-1.74

L Control 1.143 0.58-2.23 0.88 0.45-1.74



Figure 7-7: Cox regression of time to death (selected causes): adjusted exp(β) by practice

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

H F J E B D K G A C I LPractice

Adju

sted

exp(

B)


Control practice

As before, rank testing of the unadjusted and adjusted Cox regression coefficients by practice

showed no significant difference between intervention and control practices in time to death from

selected causes, as Table 7-7 indicates.

Table 7-7: Rank testing of practice Cox regression coefficients


practices


practices


Unadjusted coefficients 5 7.25 10 0.31

Adjusted coefficients 5.5 7 12 0.50



8. OUTCOMES: MORBIDITY

8.1 Health status

Health status was measured using the SF-36. Postal questionnaires were sent at baseline, at

one year and at two years. The effect of the intervention has been measured by the change in

the eight dimensions over the two years as described in the methods (see section 4.6.2 above).

These dimension scores have also been combined into two composite scores - the physical

health component score (PCS) and the mental health component score - and into a preference-

based single index.33 34

8.1.1 Missing data

Of the 6420 people who replied to the baseline questionnaire and who were included in the

study, some failed to answer all the questions in the SF-36 general health status questionnaire

and some did not respond at all to the questionnaires sent out at year 1 and year 2.

The intervention group had more missing data, with 15.1% of the intervention group who replied

having at least one missing value on the eight dimensions at baseline, compared to 13.8% of the

control group, and 41.8% of the intervention group also having some missing data due to non-

response or missing items at year 1 or year 2 compared to 37.5% of the control group (see Table

8-1 below).

The difference at baseline was not statistically significant, and indeed for men and for the oldest

age group (85+) the intervention group had less missing data at baseline than the control group.

However, at years one or two, the difference of 4.3%, though small, was significant and

consistent across age and sex groups.

Excluding the cases with some missing data at baseline, the relationship between baseline

health and the later occurrence of missing data, which was mainly due to non-response, was

examined by regressing the logit of the probability of missing data at year one or year two on the

baseline SF-36 single index health score. There was a small but statistically significant inverse

relationship, which was the same for both the intervention arm and the control arm.

This analysis suggests that those in better health may have been less likely to respond to

subsequent surveys than those in worse health, and the slightly higher rate of missing data in the

intervention group may therefore imply that any beneficial effects of the intervention may be

underestimated by analysing only those who responded.

Outcomes: morbidity 20/05/02 Page 40


Table 8-1: Proportion of cases with missing data on any of the eight SF-36 dimensions

Intervention group Control group

Patient group Baseline %

Year 1 or 2 %

Baseline %

Year 1 or 2 %

Age 65-74 13.5 37.0 10.5 32.9

75-84 16.5 42.8 16.0 39.7

85+ 17.0 59.1 20.6 50.2

Sex Male 15.9 42.3 16.0 38.3

Female 13.6 40.9 10.5 36.2

All 15.1 41.8 13.8 37.5

8.1.2 Results

The overall health status as measured on the eight dimensions of the SF-36 declined in both

control and intervention practice patients between baseline and 2 years (Figure 8-1 and Figure

8-2). The decline appeared to be similar in intervention practice patients and control practice

patients. With regard to health over the two years and adjusting for baseline characteristics, in

most of the eight dimensions, patients in the intervention practices tended to have a smaller

health decline than patients in the control practices. However, only in the energy dimension was

the effect significant. These results are shown in Figure 8-3 to Figure 8-11, below.

For the composite indices, both the physical health composite score and the mental health

composite score showed a stronger effect, and there was some weak evidence of a smaller

decline in health in the intervention practices (Figure 8-12 and Figure 8-13). For the SF-36 single

index there was also some evidence that the intervention practice populations had a better

outcome (i.e. a smaller decline in health-related quality of life) than the control practice

populations (Figure 8-14). The estimated relative improvement in the intervention populations

was +0.011 units (95% CI: 0.021, 0.000). The social importance of this statistically significant

difference is examined in the economic evaluation.



Figure 8-1: Change in health status (mean SF-36 scores) – control practices

0

20

40

60

80

100Physical

Social

Role physical

Role mental

Mental

Energy

Pain

General health

mean score at baselinemean score at 2 years

Figure 8-2: Change in health status (mean SF-36 scores) – intervention practices

0

20

40

60

80

100Physical

Social

Role physical

Role mental

Mental

Energy

Pain

General health

mean score at baselinemean score at 2 years



Figure 8-3: Adjusted mean change in physical functioning by practice

Fixed effects randomisation test: p=0.45

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101112

B H E A C G L I F D J KPractice

ControlIntervention

Random effects MLM: t10=0.91 p=0.38

Figure 8-4: Adjusted mean change in social functioning by practice


-12-11-10

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101112

H L D A C G B E K F I J

Practice

ControlIntervention




Figure 8-5: Adjusted mean change in physical role by practice


-12-11-10

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H A D I B G C K F L E J

Practice

ControlIntervention


Figure 8-6: Adjusted mean change in emotional role by practice


-12-11-10

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H B D E J G F A I C K L

Practice

ControlIntervention




Figure 8-7: Adjusted mean change in mental health by practice


-12-11-10

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H D B J E A G C L F K I

Practice

ControlIntervention


Figure 8-8: Adjusted mean change in energy by practice


-12-11-10

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B C H A D E F I J K L G

Practice

ControlIntervention




Figure 8-9: Adjusted mean change in pain by practice


-12-11-10

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H B I C F G K A D E L J

Practice

ControlIntervention


Figure 8-10: Adjusted mean change in general health perception by practice


-12-11-10

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101112

H B A C D E L J I G K FPractice

ControlIntervention




Figure 8-11: Adjusted mean change in “extended physical functioning” by practice


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101112

B H E A G C I D L J F KPractice

ControlIntervention




SF-36 composite scores

Figure 8-12: Adjusted mean change in mental health component score by practice


-12-11-10

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101112

B H D E A C K F J I G L

Practice

ControlIntervention


Figure 8-13: Adjusted mean change in physical health component score by practice

Fixed effects randomisation test: p=

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101112

H B A C D E I K F G L J

Practice

ControlIntervention

Random effects MLM: t10= p=



Figure 8-14: Adjusted mean change in single health index (x 100) by practice

-5.00

-4.00

-3.00

-2.00

-1.00

0.00

1.00

2.00

3.00

4.00

5.00

A H C B D K E I L G FPractice

Chan

ge in

sing

le he

alth

inde

x (x1

00)

Control

Intervention

Fixed effects randomisation test: p=0.07 Random effects MLM: t10=2.2 p=0.05

8.1.3 Taking exercise

One reason why only small and usually insignificant effects in the intervention practices might

have been detected is that only a small proportion of those patients who took part in the follow-up

surveys actually took any exercise. It, therefore, seems appropriate to examine any benefits of

the intervention separately in those who took exercise and those who did not.

As argued earlier, however, such analysis is troubled by selection biases. This would be

particularly true for any comparisons between those who took some exercise but stopped and

those who continued, since the reason for stopping may have included the self-perceived

outcome. On the other hand, comparisons between those who started exercise, whether or not

they carried on, and those who never started cannot be biased by selection by outcome. Of

course these are somewhat different groups of patients (see section 6) with ever-exercisers

including more younger patients and more women, for example, than never-exercisers. However,

to some extent these differences may be taken into account by case mix adjustment and the

results of such an analysis are shown in Table 8-2 below.

This shows that never-exercisers had almost exactly the same outcomes as controls, but that

ever-exercisers usually had significantly better outcomes.



Despite the adjustment for casemix differences in terms of baseline dimension score, baseline

physical activity score, age, sex, smoking status, living alone and type of accommodation, we

recognise that these results are difficult to interpret. Nevertheless the fact that ever-exercising

hasn't simply split the group of patients in the intervention practices into those who do better than

the average control and those who do worse, but rather has split them into a group who do

identically as well as controls, and a group who do significantly better does suggest that there is

some real effect.

Table 8-2: Adjusted mean effect of intervention on health status for “never-exerci

report of the exercise study - university of sheffield/file/...than men, younger than older, and...

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