Evidence and controversies

It is vital that practice nurses keep up to date with the latest evidence in order to offer the highest standards of care to their patients – but what should you do when the evidence base keeps shifting?

As practice nurses and nurse practitioners, on the frontline of primary health care, it is of paramount importance that we deliver individualised health care that is underpinned by current research and evidence. As well-informed professionals such evidence not only enhances our knowledge, skills and abilities but through its application supports best practice.

But where do we get this evidence? Can we rely on its relevance to our practice? Is it up to date? Can we trust it?

Can we really trust it? How do we know if the evidence from studies is flawed, biased or just plain wrong? How do we, as clinicians, determine what is good evidence and what needs to be viewed with caution? It’s worth taking a look at a few cases to see where the ‘evidence’ can sometimes be controversial and how that controversy can impact on our practice.

INFLUENZA VACCINE

Earlier this year, the British Medical Journal (BMJ) published an article that called into question the policy behind the United States influenza vaccination campaign.¹ The article’s author, Peter Doshi, claimed that the US Public Health Agency, the Centers for Disease Control (CDC), used flawed evidence to support the national campaign that was aimed at the population in general, not just those at risk. In so doing, he suggests that the campaign over-exaggerated the risks of influenza to the general public in order to promote and market the vaccine. Statistics from the studies – undertaken by academic and government researchers, non-commercially funded and published in high profile peer-reviewed journals – indicated that influenza vaccine reduces the risk of death by up to 48%. This led to the CDC advertising poster to state, ‘Vaccines for adults can prevent serious diseases and even death’. Inevitably, the ensuing USA media coverage further exaggerated the risks of influenza mortality and benefits of the vaccine to the healthy population. Doshi’s article questioned the credibility of the studies for having a ‘healthy-user’ bias, but in addition claimed there was ‘virtually no evidence’ to support even vaccinating the elderly in terms of reducing mortality, which was the original premise for the CDC policy on vaccination back in the 1960s. Commentary in the BMJ argued that there were data to support the effectiveness of influenza vaccination in the older population, even if the studies behind the CDC policy didn’t demonstrate this fact themselves.² However, there does appear to be a lack of evidence to support vaccinating the ‘worried well’.³ In essence, Doshi criticises the CDC campaign for ‘selling influenza’ to the American population in order to increase uptake of the vaccine, based on a policy supported by limited evidence. He suggests that it is another case of ‘disease mongering’ – to medicalise the normal life of the vast majority of healthy people, which results in unnecessary over-treatment and waste of resources.

Although this was an American campaign, as practice nurses here in the UK we are all too familiar with the demands of the ‘worried well’ during ’flu season. Such evaluation of the studies in the medical journals not only make interesting reading but equally the controversy is thought provoking in terms of its relevance to our practice.

BREAST CANCER SCREENING

The debate over benefit versus harm of screening for breast cancer has been an almost constant battle in the medical journals for the last 10 years or more. On one hand, studies have demonstrated an over-diagnosis of breast cancer as a result of breast screening.⁴ This suggests that some women have undergone unnecessary treatment for asymptomatic disease, which would would not have developed into a significant risk to health or life expectancy if left undetected.⁴ Such studies have brought into question the benefit of the Breast Screening Programme as a whole. On the other hand, researchers argue that the lives saved as a result of breast cancer screening override any harm of over-diagnosis and the resulting over-treatment, associated anxiety and distress.⁵

Last year The Lancet published a report of an independent review of the benefits and harms of Breast Cancer Screening commissioned by Cancer Research UK and The Department of Health to address the controversies.⁶ The expert panel, led by Sir Michael Marmot, Professor of Epidemiology and Public Health and Director of the Institute of Health Equity, University College, London, reviewed a number of randomised controlled trials, focussing on the incidence of breast cancer in the UK, considering internal bias, relevance and reliability of the studies. In the final report, the panel concluded that mammography does indeed prevent 1,300 deaths from breast cancer per year but acknowledged that for every death prevented, approximately three women would be over-diagnosed and over-treated. In overall terms, the report stated that ‘of the 307,000 women (aged 50-52 years) who are invited to begin screening each year, just over 1% would have an over-diagnosed cancer in the next twenty years.’⁶ Ultimately, the report concluded that the evidence does support the continuation of the UK Breast Screening Programme, despite the incidence of over-diagnosis, but there is a need to ensure that all women attending screening are made fully aware of the benefits and potential harm of breast screening in order to make an informed decision about whether to attend for screening or not. As a result, Public Health England has produced an updated NHS Breast Screening leaflet to help women decide for themselves.⁷

So, has this new report put an end to the debate? It appears not. Numerous editorial comments, correspondence and a number of articles in the BMJ over the past few months have challenged the findings in the Marmot report. It has been suggested that the over-diagnosis of breast cancer has been underreported;⁸ the studies which were reviewed by the panel are outdated and limited and therefore discredit the findings of the report;⁹ and unnecessarily treating women with radiotherapy increases their risks of ischaemic heart disease and lung cancer.¹⁰ And this controversy hasn’t been hidden from the public. Alarmist headlines such as ‘Breast cancer screening cannot be justified, says researcher’ and ‘Breast cancer screening "harming thousands” ’ appeared in national newspapers last year.^11,12 The differing opinions from the experts, and the resulting publicity, may affect our consultations with women when discussing breast screening and as practitioners we need to be fully informed of the facts if our patients challenge the value of the Breast Screening Programme.

HORMONE REPLACEMENT THERAPY (HRT)

Published between 1997 and 2003, the findings of three major studies – the Collaborative Reanalysis (CR), the Women’s Health Initiative (WHI) and The Million Women Study (MWS) – linked the use of HRT with an increase in the incidence of breast cancer.^13–15 As a result of this evidence, the use of HRT declined significantly and GPs and practice nurses changed their advice and practice of the management of perimenopausal symptoms in women. Over the past 10 years or so, many women with perimenopausal symptoms have largely been managed successfully by non-hormonal methods, through improvements in diet and lifestyle, to help them through the menopausal transition. However, recent research has suggested that the evidence from the original studies has been conflicting and has been called into question. One of the criticisms has been that the participants in the MWS observational study had a ‘detection bias’ as recruits were taken from the Breast Screening Programme, where over-diagnosis of breast cancer has already been highlighted. In addition, women diagnosed with breast cancer in the first few months of the trial were not excluded from the final data although the cancers in these women would have already been in existence prior to the study. These factors suggest a higher rate of breast cancer would have been evident in the study compared to the general population.¹⁶ Further evaluation has demonstrated limitations of the major studies, deeming the evidence linking HRT to an increased risk of breast cancer as unreliable.^17,18 An expert panel has reviewed the earlier research and conducted further clinical trials to provide more accurate evidence. As a result of this review, the British Menopause Society and Women’s Health Concern have issued recommendations on hormone replacement therapy, published in May this year.¹⁹ These recommendations inform practitioners and women alike of the pros and cons of HRT, as well as the benefits and limitations of complimentary therapies, in addition to diet and lifestyle changes and give women more options in their management of menopausal symptoms. Although it is unlikely that HRT will return to its former heyday, the evidence presented now may make practitioners and women less wary of HRT, especially with today’s lower dose regimes, than they have been in the past ten years.

MMR

An article on evidence and controversies cannot ignore what must surely be the greatest controversial study in recent times. It is useful to remember the facts. Published in The Lancet in 1998, Andrew Wakefield suggested that the MMR vaccine could be linked to an increased risk of autism and gastrointestinal disease following a study of 12 children. Despite other published studies finding no such correlation, Wakefield and his colleague O’Leary continued to pursue their research, presenting their evidence to the US Congress in 2000 based on a study of 25 children. By then, uptake of the vaccine was falling significantly and by 2003-4 only 80% of 2-year-olds in the UK had received MMR vaccine, compared with the World Health Organization’s recommendations that 95% need to be vaccinated in order to prevent an outbreak of measles.²⁰ Numerous reputable studies, demonstrating no link between the vaccine and autism and bowel disease, were being published in the BMJ, The Lancet, the New England Journal of Medicine and Pediatrics. In 2007, the GMC began fitness to practise hearings against Wakefield, and in 2010, after being found guilty of serious professional misconduct, he was struck off the medical register, and The Lancet retracted his original paper. Throughout this time healthcare professionals had to deal with the fall-out of his ‘evidence’ with falling uptake of MMR vaccine, anxious parents requesting single vaccines of mumps, measles and rubella, and the general frenzy whipped up by the popular press. The fall-out of this remains to this day.

Fast-forward to 2013. We have all been acutely aware of the measles outbreak, which started last November, across England and Wales. As a result the National MMR vaccination catch-up programme was announced in April to specifically address the high rate of unvaccinated children. Early data suggests that approximately 50% of these previously unvaccinated children have now received their first MMR with a similar number of partially immunised children having now received their second dose as a result of the campaign.²¹ Practice nurses have certainly been busy. Fifteen years after the ‘evidence’ was presented, it appears that confidence in the MMR vaccine is beginning to return.

TRUSTING THE EVIDENCE

So can we trust the evidence we have available to us? The examples above have clearly had an impact on our practice and our patients and no doubt have caused confusion and controversy for us as health professionals and indeed, for the general public.

Throughout our daily work, we constantly look to the evidence that is available. There is a wealth of evidence-based national resources, and guidance is easily accessible, at the click of a mouse, and used in our everyday practice (see Box). The web pages of such resources are very open and transparent in detailing the evidence that underpins their guidance, the rigorous processes that are undertaken to validate the evidence and the partnerships with expert bodies to support and maintain standards of excellence in their particular field.

The National Institute for Health Research (NIHR), funded by the Department of Health, enables cutting-edge research to be conducted in the UK, relevant to our healthcare needs to improve the health of our patients. This world-class research, conducted by leading professionals, is made easily accessible through NHS Evidence, as is the evidence used to underpin guidance from organisations such as NICE and SIGN. The Medical Research Council, a publicly funded organisation, supports research to ‘improve human health through world-class medical research’ with the priority of improving clinical practice and the health of the population as a whole.²² Research is essential to improve health care in the NHS and the ‘OK to ask’ campaign for 2013-14 is actively encouraging patients to be aware of local research and clinical trials and encouraging them to take part in clinical research to improve NHS care.

THE ROLE OF THE MEDIA IN CONTROVERSIES

As we know, patients are interested in health related research. Often, however, ‘evidence’ is presented through the eyes of the press. We all have patients who wave cuttings from newspapers or tell us what they’ve seen on the television the night before. Certainly the MMR scandal was played out very publicly by journalists. The media have such an enormous influence on how people view health, disease, treatments and the NHS as a whole. The blind faith some patients have in brazenly fallacious headlines can be alarming. How do we see ‘the wood from the trees’ and remove the sensationalism by the media to present the facts about the ‘evidence’ more accurately? A useful tool to direct patient to is the NHS Choices website. Its ‘Behind the Headlines’ page takes news bulletins and looks at the research on which the headlines are based and presents a more balanced view of the evidence. I personally found this particularly useful when a patient presented me with a newspaper cutting about a link between statins and type 2 diabetes and I was able to use the site to explore the evidence with the patient. Controversies often present themselves to us when we least expect it in a 10-minute consultation.

CONCLUSION

As clinicians we strive to deliver health-care with robust evidence to support our practice. On a day-to-day basis, are we truly in a position to examine the small print behind the studies to verify their validity? Clearly, there are studies that are controversial and, as seen, these can certainly impact on our practice. In reality, we rely on trusted resources to ‘deliver care based on the best available evidence’.²³ We attend seminars and study days presented by eminent speakers in the field; we read journals to update our knowledge and make ourselves aware of current issues within Primary Care; we undertake online training and further education and we apply this knowledge to our daily practice to benefit patient care. It is prudent to remain open-minded about research and to listen to and be aware of differing and challenging opinions – and to be aware that today’s evidence will continue to evolve.

REFERENCES

1. Doshi P. Influenza: marketing vaccine by marketing disease. BMJ. 2013; 346: 3037. Available at: http://www.bmj.com/content/346/bmj.f3037

2. Newall A T. Rapid Response Re: Influenza: marketing vaccine by marketing disease. BMJ. 2013. Available at: http://www.bmj.com/content/346/bmj.f3037/rr/647944

3. Nichol K. Challenges in evaluating influenza vaccine effectiveness and the mortality benefits controversy. Vaccine. 2009; 27: 6305-6311

4. Jørgensen K J, Gøtzsche P. Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ. 2009; 339: b2587 Available at: http:// www.bmj.com/content/339/bmj.b2587

5. Duffy S, Tabar L, Olsen A H, et al. Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomised trial and from the Breast Screening Programme in England. J Med Screen. 2010; 17: (1) 25-29.

6. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet, 2012; 380 : (9855)^1778-1786

7. Public Health England. NHS Breast Screening: Helping You to decide. Available at: http://www.cancerscreening.nhs.uk/breastscreen/publications/ia-02.html

8. Hawkes N. Breast screening is beneficial, panel concludes, but women need to know about harms. BMJ. 2012; 345: e7730 Available at: http://www.bmj.com/content/345/bmj.e7330

9. Kirwan C C. Breast cancer screening: what does the future hold? BMJ. 2013; 346: f87 Available at: http://www.bmj.com/content/346/bmj.f87

10. Baum M. Harms from breast cancer screening outweigh benefits if death caused by treatment is included. BMJ. 2013; 346: 346f385. Available at: http://www.bmj.com/content/346/bmj.f385

11. Boseley S. Breast cancer screening cannot be justified, says researcher. The Guardian 2012 January 23. Available at: http://www.theguardian.com/science/2012/jan/23/breast-cancer-screening-not-justified

12. Adams S. Breast cancer screening ‘harming thousands’. The Telegraph. 2012 October 29. Available at: http://www.telegraph.co.uk/health/healthnews/9641609/Breast-cancer-screening-

harming-thousands.html

13. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet. 1997. 350: 1047-1059

14. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288: 321-333

15. Million Women Study Collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet. 2003; 362: 419-427

16. Panay N. Commentary regarding recent Million Women Study critique and subsequent publicity. 2012; 18: (1) 33-35

17. Shapiro S, Farmer R D T, Stevenson J C, Burger H C, Mueck A O. Does hormone replacement therapy (HRT) cause breast cancer? An application of causal principles to three studies. J Fam Plann Reprod Health Care. 2013; 39: (2) 80-88

18. Rees M, Currie H. The British Menopause Society Fact Sheet: Explaining risk and study design. 2007 Available at: http://www.thebms.org.uk/factdetail.php?id=9

19. Panay N, Hamoda H, Arya R, et al. The 2013 British Menopause Society & Women’s Health Concern recommendations on hormone replacement therapy. Menopause Int. 2013; 19: (2) 59-68

20. Health Protection Agency. Why is MMR preferable to single vaccines? 2013. Available from: http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/MMR

21. Public Health England. Measles cases remain high as MMR campaign makes progress. [Press release] 2013. Available from: https://www.gov.uk/government/news/measles-cases-remain-high-as-mmr-campaign-makes-progress

22. Medical Research Council [about us page on the internet]. c2013 [updated 2013; cited 2013 August 3]. Available from http://www.mrc.ac.uk/About/Missionstatement/index.htm

23. Nursing and Midwifery Council. The code: Standards of conduct, performance and ethics for nurses and midwives. London: NMC, 2008.