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FOUNDERS’ LECTURE

Patient Compliance and the Placebo Effect Anne Walker

Introduction When one reads the historical evidence of how the profession of physiotherapy has developed, one is struck by the characteristic qualities possessed by a whole range of physiotherapists, from the Founders themselves to the members of the pro- fession today; qualities that include vitality, humour, resilience, tenacity and so essentially integrity. Despite the challenges and problems that have arisen and been overcome in developing the physiotherapy profession over the past hun- dred years, I am sure it would be of no surprise to our Founders to see that physiotherapy, world- wide, is one of the most prominent and focused professions in the health care arena of today.

Membership has grown to over 26,000 in Great Britain with between 4,000 and 5,000 of those members in private practice. There are almost 3,000 students in our physiotherapy training schools. Yet although these numbers may seem large, when one considers the scope of practice of modern-day physiotherapy, there is a shortfall of qualified staff working in the NHS which can only get worse. Tackling this issue may be one of the greatest challenges for physiotherapists a s we move into the 21st century.

As the profession has progressed, physiothera- pists have quite appropriately developed ski l ls to intervene in an increasingly wide range of condi- tions and to much greater proportions of the pop- ulation.

It is very encouraging that the elderly population are living healthier and longer lives although this inevitably does increase the numbers of poten- tial patients requiring physiotherapy interven- tion. At the same time i t has to be remembered that with more sophisticated ante-natal care, pre- mature babies are now surviving a t much earlier gestation and this in itself can perpetuate the overall numbers of children with profound dis- abilities. Both these factors combined with the ever-increasing referrals for physiotherapists to treat problems besetting the middle-aged and working population, ensure that the profession, with its finite resources, has to be much clearer on

which interventions for which client group pro- duce the most effective outcome, with maximum health gain accrued, not only for purchasers and providers of service, but similarly for referrers, patients and their carers.

Gradually more scientific evaluation of our inter- ventions is being undertaken and we are slowly becoming much clearer on which treatment modalities are more, or less, effective, and why. The critical factor, we know, is the detailed, thor- ough and systematic assessment, the findings of which can then inform the physiotherapist suf€i- ciently to a t least begin a dialogue with the patient on the intended plan of action, approxi- mate timescale of intervention and in some cases an initial discussion on the intended outcome.

But what about other criteria which influence a positive outcome? This lecture considers how patient compliance, and possibly the placebo effect, may play a much greater part than we often appreciate in securing a truly successful episode of care.

Patient Compliance Patient compliance is the extent to which patients do or do not follow their therapist’s advice and the factors that affect this. Our Founders, too, iden- tified compliance as an important component in the treatment process - with the predominantly Bands-on’ emphasis one can appreciate the neces- sity for an empathetic rapport with patients.

As early as 1908 an article in a nursing journal ended with the words ‘The most important attribute of the masseuse is the intangible faculty of not annoying the patient’; and in the early 1900s the old rhyme of Dr Fell seemed to be particularly appropriate when considering the relationship between masseuse and patient.

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‘I do not like you Or Fell, The reason why I cannot tell, But this is so. I know full well,

I do not like you, Or Fell’.

I 1 Not only is the therapist’s personality a crucial factor but this rhyme indicates how the therapist- patient relationship can succeed or fail, depend- ing on the care that the therapist takes in

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understanding the needs and circumstances of her patients.

Bourne’s quote in 1980 ‘War brings out the best and the worst in people, and so does illness’ seems to capture, too, from those early days of our Founders to health care in the 199Os, the essen- tial role of physiotherapists in meeting the psy- chological needs of their patients. On a similar note, Florence Nightingale is quoted as saying in 1916: ‘There is a need for the masseuse to con- vince her patients of how much can be accom- plished by hope and courage’ (Wicksteed, 1948). One can imagine the horrific injuries that these masseuses would have been dealing with and how real progress would have been impossible without co-operation from the patients.

So what are the factors that affect compliance?

Situabonal factors Treatment regime Nature of the illness Understanding Remembering Therapist-patient relationship

An individual’s unique circumstances influence his decision to comply with medical advice or not. Does the patient ‘wish’ to recover normal func- tion? He may be influenced by, for example, loss of employment or a compensation case. Compli- ance will also be related to the costs, convenience and benefits to the individual and services should be planned taking these factors into account.

The treatment regime influences the degree of compliance in many ways; patients are likely to adopt the portion of the prescribed treatment that causes least disruption to family routines. The complexity of the regime is shown to decrease compliance as is the frequency and time of day of undertaking specific elements of the programmes.

In many instances patients cannot comply with the treatment plan unless their carers are also fully participative. The ethos of giving patients lengthy and repeated courses of a treatment modality have thankfully long since disappeared and the emphasis for therapists with all client groups is to help patients with their carers in self management of the problem. This is particularly important when patients present with complex chronic or deteriorating conditions.

The nature of the illness is shown to affect com- pliance; studies indicate that as illness passes the acute stage, patients seem less likely to adhere to the treatment regime (Kent and Dalgleish, 1983). Similarly, the evidence also shows that as

symptoms reduce, compliance decreases, which might raise the issue for physiotherapists on when is the optimum time to discharge patients from an episode of care. A busy therapist may not always detect the patient’s lack of understanding. One study found that 60% of patients misunder- stood their doctors’ verbal directions about the method of taking medication (Boyd et al, 1994). This may be due to poor and inadequate expla- nations but also because patients do not always ask questions when they are unclear about the advice that they are being given.

I t is also easy to overestimate patients’ knowl- edge, or written material given to patients may be too difficult to understand. Britain is a multicul- tural society and has to address the differences in prevalence and in perception of diseases between ethnic groups. Behaviour is important as well as language.

Patients’ beliefs about the efficacy of a particular treatment may also relate to their understand- ing of their condition. Even if both patient and therapist agree and accept the initial diagnosis, there also has to be agreement about the treat- ment if it is to be implemented successfully.

Another factor to be considered is memory; differ- ent studies have shown that patients had forgot- ten 50% of information within five minutes and up to 60% immediately after the treatment ses- sion. It is also well documented that the number of statements forgotten, increases with the num- ber given, so a patient may remember three out of four statements, but only four out of eight (Hulka et al, 1976). People remember best what they hear first. Recall of instructions also increases if advice given is specific, for example You must lose seven pounds’, rather than the general statement ’You must lose weight’. Patients given specific instruc- tions recalled 49% of the advice, whereas patients given general recommendations remembered only 19% (Hulka et al, 1976).

The patient-therapist relationship is of the utmost importance if intervention is to be effective. Many patients will have little knowledge of the princi- ples of diagnosis and treatment and as physio- therapy intervention is unlikely to give immediate relief from physical symptoms, the quality of the relationship is the main source of information available to the patient about the therapist’s skill. Studies give significant support to the hypothesis that patient’s satisfaction and compliance are closely related to the doctor’s or therapist’s show of interest and concern (Bond et al, 1976; Hulka et aZ, 1976). In addition, patients were more likely to turn elsewhere when they felt dissatisfied with the personal aspects of their care, rather than the technical aspects.

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Although there has to be a certain onus on the patient to ask for clarification or for some instruc- tions to be repeated, therapists themselves may be guilty of not imparting enough information or gauging how much information to give a t each session.

The Placebo Effect Perhaps not too surprisingly, patient compliance and the principles of the placebo effect appear to be closely inter-related. When considering the def- inition of the placebo effect - ‘those effects of a treatment tha t are not attr ibutable to the mechanics of the treatment itself, but rather to the circumstances surrounding it’ (Richardson, 1994) - one can begm to accept that such factors as environment, attitude and responsiveness to the patient’s mood, even the time and day of the appointment, can influence the outcome.

I t is now widely documented and hopefully accepted that the placebo effect can be extremely powerful and is clearly worthy of investigation in its own right (Broome, 1989). This is not to say tha t placebos within physiotherapy should replace conventional treatment, but when appro- priate and used as an adjunct, the effect from the placebo may be the most effective component of the treatment package.

Without doubt if the therapist gains the patient’s confidence and trust , he will be more amenable to the therapeutic intervention and indeed one would have to question a therapist’s suitability for the job, if patients did not feel better for the consultations.

That may seem rather a trite and obvious state- ment when speaking to a predominantly physio- therapy audience, but there are many people who continue to believe that pain relief occurring after a placebo is evidence t h a t the pain is not real and should be used to ‘catch’ malingerers!

Other placebo misconceptions a re listed here which are extracted from the Turner et a1 study in 1994 on ‘The importance of placebo effects in pain treatment and research’.

Less than one third of patients will have a placebo response. Placebo effects are necessarily brief. There are placebo responders and non-responders Placebo responders had nothing wrong with them. Giving a placebo = doing nothing.

Scientific interest in the placebo effect arose largely through the introduction of the placebo-

controlled trials in the 1950s as a means of assess- ing the efficacy of drug treatments, but what place can it have in the physiotherapeutic management of patients? There are three main groups of vari- able which influence placebo responsiveness: those concerned with the patient, the treatment itself and the therapist.

The research appears to indicate that there is no ‘typical placebo reactor’ and tha t different indi- viduals may respond on different occasions. Although, if individual characteristics do exist, they probably interact with a range of other situational variables, eg anxiety, beliefs about particular treatments, and so on.

Personality factors have been shown to be related to patients’ reports of the alleviation of pain. Those patients who scored highly on the neuroti- cism and extroversion scales gave consistently higher reports of pain and were strongly affected by the analgesia, whereas medication seemed to have less effect on those patients who scored low on both scales (Kent and Dalgleish, 1983).

Placebos have been administered in many forms. The sugar pill is probably t h e most popular stereotype, but placebos which make use of sophisticated scientific equipment produce the most compelling findings with greater placebo responsiveness (Broome, 1989). Interestingly, unusually high improvement ra tes have been reported following placebo surgery where the patient receives nothing other than the operation scar.

A good example of a current modality accepted by mainstream medicine which may be no better than placebo is transcutaneous electrical nerve stimulation (or TENS). Deyo et a1 in 1990 stud- ied TENS alone and combined with an exercise programme in the treatment of chronic low back pain. They found that TENS was no better than placebo and added nothing to exercise alone. This supports the conclusions from Petrie and Hazle- man (1985) who demonstrated high credibility for a version of sham TENS, incorporating a visual display and strong verbal suggestion. The supporters of TENS may well argue tha t these findings were due to improper TENS technique, but i t does challenge us as physiotherapists to retain objectivity when continuing with our long cherished treatment modalities.

Therapist variables also appear to have an influ- ence on placebo responslveness. For example, placebos administered by professionals of high status and reputation have been reported to work better than those by lower s ta tus individuals (Lesse, 1962).

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Additionally, when the therapist’s att i tude and behaviour suggests seiious interest in the placeho effect of t h e t rea tment , t h e success rates are increased (Richardson, 1994 I .

The placebo effect therefore will he enhanced by the following factors:

Strong belief Empathy Time lndividualised treatment

I t seems that physiotherapy by t h e very nature of i ts sympathetic and tactile emphasis of work, has a special obligation to enhance t h e placebo a n d maximise a positive effect.

Maximising the Benefits of Physiotherapeutic Intervention How can physiotherapists use these two concepts of pa t ien t compliance a n d t h e placebo effect to best advantage, without compromising in any way t h e highly specialised analytical a n d technical skills t h a t physiotherapists possess, yet at t h e same time acknowledging a n d meeting the ever increasing needs of a n ever expanding population within the constraints of a finite resource?

One might be tempted to support Voltaire in his supposition ‘The a r t of medicine consists of amus- ing t h e pa t ien t while n a t u r e cures t h e disease’ (Radley, 1992), but if that were true it would be a n extremely expensive pastime. The costs of health care today are such that whichever government is in office, a n d whatever organisational arrange- ments a re introduced to buy or provide care, sup- ply will never be able to match the total needs and expectations of the population.

As thma is just one example where t h e costs of treating the condition are enormous. In 1992193 3-4% of the adul t population a n d 5-15% of children were affected. T h e cost of hospital admissions for t h e condition was 283 million, and the cost t o primary care was E320 million.

Justifiably there has been a central focus on t h e management of this condition. The British Tho- racic Society (1992) Guidelines have resulted in t h e production of auditable clinical s t anda rds , as thma clinics have been established in primary care and the interfaces between primary and sec- ondary care have been examined and improved upon. Yet in many areas physiotherapists a re not contributing to the long-term management of this condition. So far as I a m aware , practice nurses are doing a n excellent job in improving inhaler

techniques a n d t ( % a c 11 i xi fi r.c>g:u I u r spi roniet ry hut what of breathing pattern r(.-education, relax- ation, prevention of honchospasm. rfTective spu- tum clearance and increasing exercise. tolerance - these are areas of clinical management that seem unlikely to he addressed unless a physiothera- pist is part of the team.

Purchasers realise i t is essential to scrutinise ser- vice provision for those conditions which a re expensive, are long-term and affect large numbers of t he population. Back pain, incontinence a n d arthritis immediately spring to mind a s examples of conditions which absorb a great deal of phys- iotherapy time. It is impossible, however, to make a n informed decision on whether a condition could be better managed unless the current ways of pro- viding that service a re completely unravelled and examined in the context of demography, geogra- phy and other relevant local criteria.

Health care advances have improved longevity and a whole range of conditions, if not always pre- ventable or curable, a re now much more satisfac- torily managed, hopefully in a sett ing of t h e patient’s choice. Some would conclude that much of the work undertaken by physiotherapists will be of a n acute nature, but a s can be seen from the list of examples below, there a r e also a whole range of potentially chronic conditions which will benefit from physiotherapy intervention.

This i s where pa t ien t compliance and placebo effects will become so critical; problems arising from these conditions will often affect people for the rest of their lives and i t would seem that phys- iotherapists have a wide range of skills a n d knowledge to ensure that families a re maximally l iberated from t h e mental and physical con- straints placed upon them by disability and hand- icap. Once t h e acute phase of t rea tment h a s ceased the emphas is of work will be on coping strategies, teaching safe handling and moving and enabling, wherever possible, the patients to manage their own physical difficulties.

Yet, a re patients capable of managing the prob- lem themselves? The intuition of physiothera- pists, combined with a knowledge of family and environmental circumstances, will provide t h e answer. Emotional well-being plays a large par t i n a person’s ability to cope wi th illness a n d response to treatment will depend on a number of factors, including temperament , lifestyle a n d physical condition. All patients will require a package of intervention t h a t is owned by them and meets their personal indiL5dualised needs.

Pa t ien ts will usually have a minimum of five specific questions t h a t need to be answered during a n episode of care:

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Yet, are patients capable of managing the prob- lem themselves? The intuition of physiothera- pists, combined with a knowledge of family and environmental circumstances, will provide the answer. Emotional well-being plays a large part in a person’s ability to cope with illness and response to treatment will depend on a number of factors, including temperament, lifestyle and physical condition. All patients will require a package of intervention that is owned by them and meeta their personal individualised needs.

Patients will usually have a minimum of five specific questions that need to be answered during an episode of care:

wh&tiStheprobbm? WIIItgstMKme’

mew- @ ~Ssnncssareeftectnre’

Anmeynmlbbk? . Ha*anIpreventmhappwngagan?

The issue of service availability needs to be addressed by purchasers, a s well a s providers; patienta presenting with similar conditions often appear to respond to a wide range of therapy options. The availability of these options on the NHS is already on the purchasers’ agenda for fur- ther debate. Buying strategies continue to evolve a s work progresses on re-shaping service provi- sion. I t goes without saying that re-prioritisation of work and the design of new service specifica- tions has to be done sensitively and always in col- laboration with the providers. Success will be achieved only if there is a high level of under- standing and joint working between all key players.

Apart from the pain and physical suffering endured by people referred for physiotherapy intervention, there are also the personal burdens which will affect the patients’ state of mind and level of cooperation:

How often arc patients’ physical signs simply a manifentation of a much deeper problem? The clinical treatment becomes almost an irrelevance

with the benefits arising from the listening and empathetic counselling of the therapist.

Chronicity of a condition can occur surprisingly rapidly and physiotherapists are in a unique posi- tion to observe reducing function. Patients with heavy personal burdens may be unable to moti- vate themselves to exercise, to keep mobile or to comply with the treatment goals; in these situa- tions the skill of physiotherapists is in -&sing the non-compliant elements and adapting the treatment programme to these complex needs. In the management of children, clients with learn- ing disabilities, mentally ill patients and frail older people, the burden of care will oRen lie with families and carers, who will rely heavily on physiotherapists for training, support and expert advice and on many occasions for practical tips.

Physiotherapists will need to consider the impli- cations for those patients who do not have sup- portive and participative carers and consider how best to provide the long term treatment packages without necessarily using expensive and special- ist resources. Physiotherapy assistants are a vital adjunct to our professional workforce; it would be impossible for staff to carry the size of caseload that is now expected by senior managers without delegation to well trained and high quality assis- tants. Ongoing skill mixing of staff both within and across professions is essential if the expert skills of physiotherapists are to be appropriately developed to meet the wider needs of the popula- tion.

And so to physiotherapists’ relationships with other health care professionals. Good health care management has to be about partnerships and teamwork. An essay written only eight years ago by an eminent London professor on ‘Fostering good communication between doctors and para- medical staff included this paragraph:

‘A good model is a weekly meeting in a side room, near the ward. over a light lunch, discussing all the patients with the paramedical team. These are prof- itable and happy occasions when everyone can read- ily take part. A sense of humour is indispensable in running a happy unit, but not all humour is helpful. Physiotherapists do not appreciate receiving a request for post-operative physiotherapy specifying ‘slap and tickle please’ (McColl, 1986).

I have greater faith in a discussion document pub- lished by the Royal College of General Practition- ers in (Pereira Gray, 1992) which emphatically states that nurses, therapists and doctors should increasingly aim to work together in order to complement each other’s work. Physiotherapy managers are continually exploring ways of pro- viding more imaginative and wide-reaching ser- vices and one of the advantages of focusing the

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A desire to participate in regular clinical audit

To be prepared to reccgnise the contribution that alternative therapsts can offer in the management of selected conditions

To begin the process of moving resources away from traditional hospital settings when length of stay is shortening

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service on primary care might result in a more clearly defined role for physiotherapists in pre- ventive work while at the same time integrating with other professionals to provide a much more systematic approach to the management of chronic disease.

Prevention and Health Education I t does appear that the area of prevention has not been sufficiently targeted by the profession and yet there is so much scope for physiotherapy involvement particularly in compiling and initi- at ing training packages for colleges, the work- place and in schools.

Two studies by Armstrong et a1 in 1990 concluded that British school children have surprisingly low levels of habitual physical activity, with many children seldom undertaking the volume of phys- ical activity required to stimulate and therefore benefit the cardiopulmonary system. Physiother- apists acting in a consultant capacity to schools would be in an ideal position to introduce children and staff to the benefits of exercise programmes, at the same time advising on back care, joint protection and a range of other topics which can prevent long-term problems in adulthood and later life.

Further developing preventive programmes, meeting the Health of the Nation targets and empowering consumers to feel more involvement in the Patient’s Charter and other broad quality issues in the NHS are now on-going pieces of work for purchasers and providers across a range of agencies.

The Future But what other developments might we expect to see as we head towards the next 100 years?

Contrnuatmn of the move to pnmary care

Greater emphasts on educatmg volunteers and carers in managing health problems Shared dements of health care tmning

Aucbtable standards for clmical management Greater use of complementary medicine

. Increased us8 of the independent sector

Useofacommondatabase

P h a n n a d ~ c a l developments

lwease in m e d d technology Development of a din& pmfesslonal team

Looking through this l ist one can see that the focus of physiotherapy intervention will continue to change as medical science, pharmacology and information technology become ever more sophis-

ticated. Day care surgery will grow in a range of settings and initiatives to care for people in their own community will become even more flexible and imaginative. Throughout these evolving years of the profession leading to our first centenary, physiotherapists have consistently demonstrated their willingness to respond to increasing health care demands; clearly, however, the time has now come where these demands for assessment and treatment are so great that the intended goals to be achieved must be agreed and shared between all parties involved in the package of care. True non-compliance from a patient may well have to influence the physiotherapist’s decision on when to conclude an episode of care.

Final Thoughts The Latin motto, Digna Sequi, inscribed on the Society’s badge and worn by all chartered phys- iotherapists, translated means ‘Pursue Worthy Aims’. Such aims for physiotherapists in the health care climate of the 21st Century must include:

To my mind the most important aim is to collab- orate with a range of health professional col- leagues including GPs and consultants to secure the development of a clinical professional team which has little hierarchy yet leadership and a complementary range of skills which are effective, responsive and, when appropriate, interchange- able across professional boundaries.

Both experienced clinicians and newly qualified physiotherapists will be integrated within the clinical professional teams. New policies and developments in health care will, and should, influence both the syllabus and the educational process by which our physiotherapists of the future are trained. Elements of the students’ cur- riculum already focus on management issues but will increasingly need to include training on the development of outcome measures, collaborative working, prioritisation of workloads and evalua- tion of health gain. In the past, physiotherapy ser- vices have often been seen as closely affiliated to departments of rehabilitation. In the future i t may be that ‘physiotherapy’ liaises more appro- priately with departments of public health, par-

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titularly contributing to the needs assessment work which is already beginning to define our caseload for the next century.

A u d h o r 8 n d A W ~ f o r ~ ~ p 1 t d e M Anne P Waker MMFCSPis Health Strategist, Exeter and North Devon Health Authority. Southernhay East, Exeter EX1 1 W.

Ack~wW?dgmmts In preparation for this lecture I wish to acknowledge the helpful assistance from Stuart Skyte and Jane Morrison in providing historical information, to the late Jane Wwteed for her detailed background book on The Growth of a Profession and to all those chartered physiotherapists who contributed to the text of 100 Ymrs of Physiottmmpy. Last, but most importantly. to my sec- retary, Mrs Jenny Lee. who patiently compiled the text into a meaningful form.

ReamW88 Annatrong, N, Bawng, J. Gentle, P and Kirby, B (19Soa). 'Pat- mdphyslcal adivityam0ng 11 to 16 year old British children', B~MedycelJW~301.203-205. Amstrong, N, Balding, J, Gentle. P and Kirby, B (1990b). 'Esti- mation of carom risk factom in British schoolchildren: A pre- l iminaryrepr, t3nWhJWma1ofSpolfSwd,ick,24,1,61a. Bond, M R, Glynn, J P and Thomas, D G (1976). 'The relation between pain and personality in patients receiving Pentazocine (Fortral) after surgery', Journal of Psychosomatic Research, 20,369-381. Bourne, S (1980). Under the Doctor shrdies in them-/ problems of physiotherapists, patients and doctors, Tavistock CIhic London. Avebury. Bopl, J R. Covington, T R, Stanaszek, W Fand Coussons, R T (1974). ' ~ ~ . ~ ~ ~ ~ ~ ~ ~ , a1 .485-491.

Brltbn ~~, m paediabic Aseociakn, Royer coc lege of Physicians d London and King's Fund Cenho (1882). Guidelhes for the MBnegement of Asthma, London.

Broome. A K (1 989). Health PsychoMy: Pnrcesses and appli- cations. Chapman and Hall, London. Deyo, R A. Walsh. N E etal(1990). 'A controlled trial of transcu. taneous electrical nerve stimulation (TENS) and exercise for chronic low back pain', New Englad Journal of Medicine~ 322,

Hulka. B S. Cassel. J C, Kupper, U and Eurdette, J A (1976). 'Communication, compliance and concordance between physi- cians and patients with prescribed medications', American Jour- nal of Public Health, 66,847-853. Kent, G and Dalgleish, M (1983). Psychologyand Medical &re, Van Nostrand Reinhold (UK), London. Lesse, S (1962). 'Placebo reactions in psychotherapy', Diseases of the Nervous System, 23.31 3-31 9. Ley, P (1979). 'Memory for medical information', British Journal of socialand Clinkal P s y d ~ w , 18,245255. Mccoll. I (1986). 'Pattnership or prejudice'. A collection of essays by a Nuffiekl Working Party on Communication. Pereira Gray, D (1992). Planning Primary Cam: A difcursiOn doc- ument, Occasional Paper 57, The Royal College of General Prac- titionem, London. Petrie, J and Hazleman, B (1985). 'Credibility of placebo tran- scutaneous nerve stimulation and acupuncture, Clinical and

Radley, A (1992). Making Sense of Illness: The social j ~ ~ y c h d - cgy of heantr and disease, Sage, condon. Richardson, P H (1994). 'Placebo effects in pain management', Pain Reviews, 1.15-32. Turner, J A et al(1994). 'The importance of placebo effects in pain treatment and research', Journal of the Am&n Medical Assodation, 271,20,160914.

W M W , J (1 948). The Growlh of a Pmibssh, Edward A ~ T I O ~ ~ , London.

1627-34.

Experimentel R b ~ m a t ~ & y , 3,151-153.