From the Labs

The CLAHRC WM Director has never been able to resolve the following paradox – when treating infections, microbial chemosensitivity is tested in the laboratory to select the antibiotic for use in the patient, but when treating cancer, in vitro chemosensitivity testing is not carried out. Part of the answer may come from a recent paper in Nature,[1] which shows that most cancers are polyclonal – they are constituted of a mix of different cell types which assist each other’s growth in a symbiotic way. So a biopsy may yield cells from only one clone and give a misleading result when tested in the lab. Of course, the bug that is cultured in the lab may also not be the one that is actually causing the disease, so the dissonance is not completely resolved.

However, cell culture is giving way to molecular genotyping for both infections and cancer. In time, the genetic signature will do more than just classify cancers and germs, but will also enable virulence and chemosensitivity to be determined. The massive organisational implications of these scientific advances at home and abroad are core CLAHRC business, as discussed earlier in this News Blog.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Murusyk A, Tabassum DP, Altrock PM, Almendro V, Michor F, Polyak K. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature. 2014; 514: 54-9.

Italian Scientists Acquited by Appeals Court

The CLAHRC WM Director was pleased to read that an appeals court has cleared six Italian scientists who were convicted for manslaughter in 2012. Their crime? Failing to provide adequate warning of a large earthquake that resulted in around 300 deaths and 1,500 injuries in 2009. The Director posted his thoughts on the initial conviction in a previous blog.

— Richard Lilford, CLAHRC WM Director

Can Ministers and Policy Makers learn anything from CLAHRCs?

My book club recently suggested that we should read ‘The Blunders of Our Governments’ by Anthony King and Ivor Crewe. I opposed their choice on the grounds that it sounded like a sensationalist polemic and, having served as a civil servant, I did not fancy a crude caricature of my erstwhile colleagues. However, I was glad I was over-ruled – the book is nuanced and makes an excellent read. It chronicles blunders made by both Labour and Conservative administrations over more than two decades. And let’s be clear – a blunder is not a bad policy in the sense that the objective is not a worthy one, but a policy that fails on its own terms. A good example is the creation of the Child Support Agency under a Conservative administration, which was then radically amended, but to no good effect, by Tony Blair’s government. Its aims were to improve child welfare by compelling absent fathers to contribute to their children’s maintenance – a laudable goal. It was for this reason that it survived successive governments of different ideology before it was finally superseded. In a nutshell, it failed through the ‘devil in the detail’. How did such a policy survive the scrutiny process in government and in both houses of parliament?

A change in policy is an example of a ‘complex intervention’ – that is to say an intervention which has many components interacting within a complex system, so that its effects are hard to predict. Good intentions are simply not enough. Scrutiny afforded the above child protection policy was simply too distant; too focussed on worthy objectives and not sufficiently diligent in scrutinising how the intervention might be propagated in a complex system. An important function of NIHR CLAHRCs is to provide such scrutiny (although they generally concern themselves with health services rather than the system / government policy level [1]). So CLAHRCs may be able to speak ‘truth unto power’ in recommending that ministers and their advisors follow a systematic process of intervention development that broadly adheres to the following steps:

  1. Ensure that your proposal is informed by a careful overview of the research literature so as to learn from the experience of others. Such a step may have warned the John Major government they were stepping into a ‘minefield’ in creating the Agency.
  2. Draw a conceptual map to explain how the intervention is supposed to work and also how it may fail or do harm, and speak to people who work in the service and who can identify ‘barriers and facilitators’. In the case of child support, such an exercise may have brought to the surface the difficulty in finding a solution that was at once workable and fair. In the event, the policy was by turns too rigid and too complicated; eventually the algorithm to calculate the amount of money a father must pay ran to over 140 pages of algebra, reflecting the difficulty in providing a just solution for people living in very different circumstances.
  3. Building on identified barriers and facilitators, an intervention should be designed with the help of the kind of people who will have to implement it and who will be affected by it. This is usually managed through a series of facilitated workshops to provide opportunities for deliberation as successive versions of a detailed implementation plan are thrashed out. Ideally two independent design teams should be deployed to see whether they come up with the same solution.[2] Such diligence may have mitigated the group thinking which led to the unrealistic requirements that the Child Support Agency should be up and running within a year.
  4. The intervention should be ‘road tested’ in a sample of sites before being rolled out (in modified form if necessary) or abandoned. Such a pilot study might have been tricky in the case of absent fathers scattered over the country and politicians may be understandably leery about testing an intervention in one region after the public relations disaster associated with piloting the poll tax in Scotland. In such a situation we recommend a whole-scale simulation of the intervention – a type of ‘alpha testing’.

Okay, this may sound pusillanimous to politicians who might be impatient to have something to show for their time in office. But the Child Support Agency collected only £15 million of additional money at a cost of £137 million in its first year of operation. It was almost universally loathed by fathers and mothers alike. The Oxbridge-educated ministers who designed the child protection policy were famously cerebral, prompting a colleague to jibe “it took exceptionally intelligent people to design a system so stupid!”

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Lilford RJ, Chilton PJ, Hemming K, Girling AJ, Taylor CA, Barach P. Evaluating policy and service interventions: framework to guide selection and interpretation of study end points. BMJ. 2010. 341:c4413.
  2. Litchfield IJ, Bentham LM, Lilford RJ, Greenfield SM. Test result communication in primary care: clinical and office staff perspectives. Fam Pract. 2014; 31(5): 592-7.

 

So it is not true what they say – traditional healers are not as widely used after all

We have all heard it said that most of the African population makes heavy use of traditional healers alongside allopathic care. According to the WHO, “up to 80% of the population [of African member states] uses traditional medicine for primary health care.”[1] However, this idea has been challenged by Kate Wilkinson, who traced the roots of the claim.[2] She found that it has been copied from document to document from its origins in a 30 year old book available in the University of Witswatersrand library. The statement in the book is not referenced, so does the trail end there? Wilkinson turned to the South African General Household Survey, 2011,[3] and found that traditional healers were the least favoured healthcare provider, comprising first choice for only 0.1% of South Africans. Even allowing for respondent bias, this is not impressive! The South African DHS survey (n=8,115) found that only 2.6% of people reported receiving care from a traditional healer and 3.1% from a faith healer, versus 20.0% reporting contact with a public sector health faculty, and 15.2% reporting such contact with a private provider.[4] Likewise a 2008 survey of households in South Africa (n=4,762) found that only 1.2% of respondents reported using traditional healers,[5] with much lower utilisation rates than public sector clinics or hospitals. Reported use of traditional healers was higher among those of a lower socio-economic status (p<0.01), who were unemployed (p<0.01), lived in rural areas, were aged between 25-49 years and reported low health status (p<0.01), although these associations are not consistent across different countries.[6] [7]

In many traditional African belief systems mental health problems are perceived as being due to ancestors or bewitchment, and traditional healers are viewed as having more expertise in these areas.[8] Maybe consultation rates are higher in mental health? A 2011 cross-sectional survey of 2,514 adult Qatari/Arab expatriates residing in the State of Qatar found that nearly 40% of respondents believed that possession by evil spirits could be a reason for mental illness, and ~50% thought it could be a punishment from God (for comparison, ~80% believed it could be caused by brain disease; ~75% by stress; ~75% by genetic inheritance).[9] The study also found that approximately 40% believed that traditional healers could treat mental illness. Other reasons for preferring to see traditional healers included the psychosocial support afforded, their availability/accessibility, the flexibility in payment (including paying after treatment, in kind, in instalments, or payment being waivered).[10] [11] A 2003 study in Tanzania found that the prevalence of mental disorders among patients of traditional healer centres was approximately twice that of patients attending primary health care clinics.[6] Meanwhile a study in Eastern Uganda found that over 80% of patients diagnosed with psychosis used both biomedical and traditional healing systems, with those combining both seemingly having a better outcome.[12] A study by Sorsdahl et al.[8] looked at care for mental health disorders in South Africa using a national survey of 3,651 adults – only 9% of the respondents reported using traditional healers (and 11% reported consulting a religious/spiritualist advisor), the use of traditional healers was predicted by older age, black race, unemployment, lower education, and having an anxiety or substance-use disorder. A number of small studies have also been conducted in sub-Saharan African countries, which showed that 41-61% of individuals with mental illness were reported to have consulted a traditional healer.[13] [14]

It seems that use of traditional healers is declining in Africa – certainly in South Africa – but that they may have a larger role in mental health. This is a point we propose to investigate under CLAHRC International using the SAGE database.

— Richard Lilford, Director CLAHRC WM;

— Peter Chilton, Research Associate;

— Oyinlola Oyebode, Associate Professor in Public Health

References:

  1. World Health Organization. Traditional Medicine. Fact sheet No. 134. 2003.
  2. Wilkinson K. Do 80% of S. Africans regularly consult traditional healers? The claim is false. Africa Check. 2013.
  3. Statistics South Africa. South African General household survey, 2011. Pretoria: Statistics South Africa. 2012.
  4. MRC South Africa. South Africa Demographic and Health Survey, 2003. Part III. Pretoria: MRC South Africa. 2003.
  5. Nxumalo N, Alaba O, Harris B, Chersich M, Goudge J. Utilization of traditional healers in South Africa and costs to patients: Findings from a national household survey. J Pub Health Pol. 2011; 32 (s1): s124-36.
  6. Sorsdahl K, et al. Traditional healers in the treatment of common mental disorders in South Africa. J Nerv Ment Dis. 2009; 197(6): 434-41.
  7. Bener A, Ghuloum S. Gender differences in the knowledge, attitude and practice towards mental health illness in a rapidly developing Arab society. Int J Psych. 2011; 57(5): 480-6.
  8. Ae-Ngibise K, Cooper S, Adiibokah E, Akpalu B, Lund C, Doku V. ‘Whether you like it or not people with mental problems are going to go to them’: A qualitative exploration into the widespread use of traditional and faith healers in the provision of mental health care in Ghana. Int Rev Psychiatr. 2010, 22(6):558-67.
  9. Mbwayo AW, Ndetei DM, Mutiso V, Khasakhala LI. Traditional healers and provision of mental health services in cosmopolitan informal settlements in Nairobi, Kenya. Afr J Psychiatry. 2013;16(2):134-40.
  10. Ngoma M, Prince M, Mann A. Common mental disorders among those attending primary health clinics and traditional healers in urban Tanzania. Br J Psych. 2003; 183: 349–355.
  11. Abbo C. Profiles and outcome of traditional healing practices for severe mental illnesses in two districts of Eastern Uganda. Global Health Action. 2011; 4.
  12. Freeman M, Lee T, Vivian W. Evaluation of mental health services in the Orange Free State. Parktown, South Africa: Department of Community Health, University of the Witwatersrand Medical School. 1994.
  13. Ensink K, Robertson B. Patient and Family Experiences of Psychiatric Services and Indigenous Healers. Transcultural Psych. 1999;36(1):23–43.
  14. Patel V, Simunya E, Gwanzura F. The pathways to primary mental health care in high density suburbs in Harare, Zimbabwe. Soc Psych Psych Epid. 1997; 32: 97–103.

The NHS “Five Year Review”. View from the West Midlands CLAHRC

We were delighted to note the emphasis on controlled studies and operational research in the NHS’s “Five Year Forward View”. CLAHRCs have taken the lead in supporting the development of new interventions and in evaluating them, and have been at the forefront of evaluations of whole-scale service change and ‘combinatorial innovation’ heralded by the report. For example, our particular CLAHRC has:

  • Documented improved access to mental health following an intervention designed in collaboration with service users.[1]
  • Developed and then evaluated an intervention to support women with social risk factors over the peri-natal period.[2]
  • Evaluated a £400m intervention to bring social housing up to minimum standards.[3]

CLAHRCs often take the lead in pilot studies that are then rolled out into national evaluations funded by competitive grants; local examples include evaluations of new IT platforms as they are introduced into NHS hospitals,[4] methods to increase access to mental health services,[5] and of increased consultant provision over weekends.[6]

CLAHRCs played a large role in applications for the AHSNs and continue to work in close alignment with these bodies, for example in developing, adapting and evaluating projects to enhance patient safety. CLAHRCs have combined intellectual rigour with the need to respond rapidly to the service timetable and have become international leaders in imaginative designs such as step wedge trials.[7]

We also applaud the emphasis on prevention and reducing disparities in the review; here again CLAHRCs are making a substantial contribution at many levels, providing state of the science evidence through systematic reviews, option appraisal (through economic models),[4] [8] [9] intervention development incorporating expertise in subjects as diverse as behavioural economics and organisational theory, alpha testing in off-line simulations and large scale intervention through randomised trials. CLAHRCs are all working with local authorities in this work and are therefore well positioned to lead evaluations where local evaluations are rolled out more widely. Our CLAHRC has contributed to the development of economic models to evaluate service change, as well as individual technologies such as regenerative medicine,[10] [11] thereby strengthening both the supply and demand sides of the health economy.

— Richard Lilford, CLAHRC WM Director

References:

  1. Birchwood M, Connor C, Lester H, Patterson P, Freemantle N, Marshall M, Fowler D, Lewis S, Jones P, Amos T, Everard L, Singh SP. Reducing duration of untreated psychosis: care pathways to early intervention in psychosis services. Br J Psychiatry. 2013; 203(1): 58-64.
  2. Kenyon S, Jolly K, Hemming K, Ingram L, Blissett J, Dann S-A, Chambers J, MacArthur C. Evaluation of Lay Support in Pregnant women with Social risk (ELSIPS): a randomised controlled trial. BMC Pregnancy Childbirth. 2012. 12: 11.
  3. Sandwell Homes. Sandwell Homes Business and Delivery Action Plan 2010/2011. 2009.
  4. Lilford RJ, Girling AJ, Sheikh A, Coleman JJ, Chilton PJ, Burn SL, Jenkinson DJ, Blake L, Hemming K. Protocol for evaluation of the cost-effectiveness of ePrescribing systems and candidate prototypes for other related health information technologies. BMC Health Serv Res. 2014. 14: 314.
  5. Marshall M, Husain N, Bork N, Chaudhry IB, Lester H, Everard L, Singh SP, Freemantle N, Sharma V, Jones PB, Fowler D, Amos T, Tomenson B, Birchwood M. Impact of early intervention services on duration of untreated psychosis: Data from the National EDEN prospective cohort study. Schizophr Res. 2014; 159(1): 1-6.
  6. Bion J, Dixon J, Evans T, et al. Stepping Up: A Phased Evaluation of the Impact of High-Intensity Specialist-Led Acute Care (HiSLAC) of Emergency Medical Admissions to NSH Hospitals. HS&DR 12/128/17.
  7. Hemming K, Lilford RJ, Girling AJ. Stepped-wedge cluster randomised controlled trials: a generic framework including parallel and multiple-level designs. Stat Med. 2014;[ePub].
  8. Lilford RJ, Chilton PJ, Hemming K, Girling AJ, Taylor CA, Barach P. Evaluating policy and service interventions: framework to guide selection and interpretation of study end points. BMJ. 2010: c4413.
  9. Yao GL, Novielli N, Manaseki-Holland S, Chen YF, van der Klink M, Barach P, Chilton PJ, Lilford RJ; European HANDOVER Research Collaborative. Evaluation of a predevelopment service delivery intervention: an application to improve clinical handovers. BMJ Qual Saf. 2012;21 (s1): i29-38.
  10. Girling AJ, Young TP, Brown CA, Lilford RJ. Early-stage valuation of medical devices: the role of developmental uncertainty. Value Health. 2010; 13(5): 585-91.
  11. Girling AJ, Lilford RJ, Young TP. Pricing of medical devices under coverage uncertainty – a modelling approach. Health Econ. 2012; 21(12): 1502-1507.

Intervention Mapping

Intervention mapping (IM) is a systematic process that uses behavioural theory and research evidence to develop specific learning and change objectives and their determinants. It consists of six steps:

  1. Needs assessment, including identification of problem behaviours, desired outcomes, and associated environmental conditions.
  2. Mapping programme objectives and determinants.
  3. Selecting techniques and strategies to modify determinants.
  4. Producing intervention.
  5. Planning for adoption and implementation.
  6. Creating evaluation plans.

Using the first four steps of the protocol Stuart Logan, Director of PennCLAHRC, and his team planned a school-based intervention to help prevent childhood obesity – the Healthy Lifestyles Programme (HeLP) – focussed on reducing sweetened soft drink consumption, increasing proportion of healthy snacks eaten, and reducing screen-based activities.[1] Although the process was time-consuming, the authors found that IM was a useful tool for developing a feasible, theory-based intervention, and that it allowed a deeper understanding of the intervention process, improving their ability to design and deliver an effective intervention. It also ensured that the behaviour change techniques and delivery methods used linked directly to the performance objectives and their associated determinants, which could then provide a clear framework for any future process analysis.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Lloyd JJ, Logan S, Greaves CJ, Wyatt KM. Evidence, theory and context – using intervention mapping to develop a school-based intervention to prevent obesity in children. Int J Behav Nutr Phys Act. 2011; 8. 73

Hyperbole

Most scientists have an instinctive dislike of hyperbole. Quite right too, according to Markowitz and Hancock [1] who have analysed the high and low rectitude papers of the famous scientific fraudster Diederik Stapel. Sure enough, the fraudulent papers can be identified with high sensitivity and specifically by the frequent usage of hyperbole (e.g. terms such as extreme, exceptionally, profoundly, vastly).

The CLAHRC WM Director always goes into a heightened state of alert when the author of a grant application he is reviewing prefaces a description of the proposed method with the word ‘rigorous’. Generally speaking, it signifies that what he is about to read is anything but!

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Markowitz DM, Hancock JT. Linguistic Traces of a Scientific Fraud: The Case of Diederik Stapel. PLoS ONE. 2014; 9(8): e105937.

Really Important Papers on Child Development

Our CLAHRC has recently conducted an individually randomised trial of the effect of perinatal (before and after birth) support from lay health workers for women at high social risk. The results have been submitted for publication, but in the meantime the BMJ has reported a 2×2 factorial RCT of an integrated early child development intervention, consisting of micronutrient supplementation and weekly stimulation through local women. The study was conducted across 96 communities in Columbia.[1] While the supplementation yielded a null result, the additional psychosocial stimulation produced marked improvements in cognition and language over an 18 month intervention period. The results partly corroborate a similar recent study reported in the Lancet.[2] This study was also a 2×2 factorial design, again of nutrition (including micronutrients) and stimulation. This study involved 80 communities in Pakistan. They replicated the findings regarding stimulation, but also recorded a positive, albeit smaller, cognitive benefits from the nutritional intervention. Babies and toddlers are little learning machines who love to interact, and benefit themselves and others by doing so. The effect of nutrition may be more context dependent.[3] Our CLAHRC is considering conducting an overview, combining studies that examine antenatal and postnatal interventions, or both, and that compare interventions targeted mainly at the mother, versus those where the infant is the primary focus of attention. In the meantime, here are two excellent cluster factorial designs of similar interventions in two different continents, serendipitously published within weeks of one another.

— Richard Lilford, CLAHRC WM Director

References:

  1. Attanasio OP, Fernandez C, Fitzsimons EO, Grantham-McGregor SM, Meghir C, Rubio-Codina M. Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: cluster randomized controlled trial. BMJ. 2014; 349: g5785.
  2. Yousafzai AK, Rasheed MA, Rizvi A, Armstrong R, Bhutta ZA. Effect of integrated responsive stimulation and nutrition interventions in the Lady Health Worker programme in Pakistan on child development, growth, and health outcomes: a cluster-randomised factorial effectiveness trial. Lancet. 2014; 384: 1282-93.
  3. Black MM & Hurley KM. Investment in early childhood development. Lancet. 2014; 384: 1244-5.

Scepticism and the Democratisation of Science

Those of us who inhabit the great ivory towers of academia sometimes forget that there is a grassroots passion for science outside the walls of our venerable institutions. I recently attended a talk organised by Skeptics in the Pub, Coventry. It was an encouraging experience, with some interesting lessons.

A speaker called Michael Marshall (no relation) is currently touring various “Skeptics in the Pub” venues. He has an unusual job description, since he is employed as a full-time sceptic by the Good Thinking Society. Backed up with a PowerPoint presentation, he gave an amusing and stimulating pitch – somewhere in the territory between Dave Gorman and Ben Goldacre.

An assortment of self-proclaimed psychics was the first subject of the talk. At first glance they seemed risibly easy targets: but it transpired that some are wealthy and famous; some even inveigle their way into families affected by tragedies such as missing children.[1] Perhaps most unsettling was that at least one had successfully sued The Daily Mail for claiming that she might be receiving instructions through an earpiece while on stage.[2] The speaker was careful not to repeat the allegation: a comment on our nation’s libel laws.

Next up was a beautifully designed and executed ‘n of 1 crossover trial’ of the effects of the Shuzi bracelet on penalty kicking performance.[3] For £59 this device claims to improve sporting prowess using “Nano Vibrational Technology” to “separate your blood cells and enhances brain cognitive abilities”.[4] I hardly need tell you the results, but the device is no longer marketed in the UK.

The final act was the story of the worldwide mass homeopathy overdose organised for 10:23am on 6 February 2011. This dramatically demonstrated that homeopathic remedies, generally diluted so much as to contain no active ingredient, can have no therapeutic effect beyond that of a placebo. The timing of the event, 6/02 at 10:23, obliged the media to explain Avogadro’s number.[5]

Are there any lessons for health care in this? The appetite for knowledge (epistemic greed) is greater than our capacity to produce it, so there is a ready market for pseudo-knowledge. The whole purpose of the scientific method and scepticism is to challenge our innate credulity. The use of the media to raise awareness was masterful. Only one of the examples in the talk is funded by the NHS, so that is progress of a sort. But most importantly, the sceptics and their fellow travellers remind us that the scientific method is not the preserve of a professional elite, it is for anyone to use.[6] The corollary is that belief in the efficacy of water imbued with quasi-spiritual properties (holy water) is not the monopoly of non-professionals.[7]

— Tom Marshall, Deputy Director CLAHRC WM, Prevention and Detection of Diseases

References:

  1. Power J. Joe Power, the man who sees dead people – Police investigations. 2013. [Online]
  2. BBC News UK. Daily Mail payout to Sally Morgan over psychic ‘scam’ article. BBC News [Online]. 2013-06-20.
  3. Marshall M. Is the Shuzi sport band a brilliant technology or a waste of money? The Guardian [Online]. 2012-09-04.
  4. Shuzi. Official Shuzi Website. [Online]. 2013.
  5. The 10:23 Campaign. The 10:23 Challenge 2011. [Online]. 2014.
  6. The Merseyside Skeptics Society. The Merseyside Skeptics Society. [Online]. 2014.
  7. Perry R, Watson LK, Terry R, Onakpoya I, Ernst E. British general practitioners’ attitudes towards and usage of homeopathy: a systematic review of surveys. Focus on Alternative and Complementary Therapies. 2013; 18(2), 51-63.

Origin and Spread of HIV/AIDS

The HIV-1 virus that went on to infect 75 million people, jumped from a chimpanzee to a human in the 1920s. This happened in South Eastern Cameroon and it then travelled to Kinshasa (then Léopoldville), from where a subtype (C) was transported to the mining town Lubumbashi (then Élisabethville) in 1937, and from there to other places in Africa. The CLAHRC WM director likely encountered cases while he was a medical student in Johannesburg. At that time AIDS was unknown. However, Congolese men who had come to work in South Africa’s gold mines presented at Baragwanath Hospital with a disease characterised by wasting opportunistic infections, and Kaposi’s sarcoma. It was given the name “slim” (meaning thin in Afrikaans) disease. Sub-type B meanwhile, made its appearance in Kinshasa around 1944 and jumped to the United States in the 1960s, and hence to the rest of the world, including Africa where the sub-types B and C now co-exist.

How do we know all this? The emergence of HIV can be traced using archive human material to create family trees (phylogenies) and place dates on the origin and branches using a molecular clock (based on the mutation rate of viral DNA).[1] [2]

— Richard Lilford, CLAHRC WM Director

References:

  1. Cohen J. Early AIDS virus may have ridden Africa’s rails. Science. 2014; 346(6205): 21-2.
  2. Faria NR, Rambaut A, Suchard MA. The early spread and epidemic ignition of HIV-1 in human populations. Science. 2014; 346(6205): 56-61.