Association and causation: the link between childhood IQ and mortality
Around Christmas, we are often more aware of the scale of poverty than at other times of the year. Everybody is talking about social inequality and its impact on health, from the World Health Organisation (WHO) to our own UK policymakers , from researchers and journalists to health professionals . The WHO defines social determinants as “...the conditions in which people are born, grow, live, work and age, including the health system. These circumstances are shaped by the distribution of money, power and resources at global, national and local levels, which are themselves influenced by policy choices. The social determinants of health are mostly responsible for health inequities - the unfair and avoidable differences in health status seen within and between countries.”
The difficulty, of course, is how to tease out what is most important in causing ill health- poverty, education, childhood social environment or family situation. If we don’t understand what are the causes and effects of these inequalities, then it becomes very hard to design coherent policies to address them. The link between childhood intelligence and health is a great example. Previous studies have suggested that intelligence in childhood and early adulthood is associated with illness and death. Note the wording: an “association” or “link” does not necessarily imply “causation”; i.e. we cannot say whether differences in childhood intelligence actually cause changes in health in later life.
There are two competing hypotheses to explain this association or link: firstly, that early IQ is the fundamental explanation for socioeconomic differences in health; and secondly, that socioeconomic conditions in childhood and adulthood are responsible for health differences linked to early IQ. In the first hypothesis, we are assuming a true association. In the second hypothesis, early IQ may be a confounder of the relationship between socioeconomic conditions and health. Whereas bias involves error in the measurement of a variable (in this case childhood IQ or mortality), confounding involves error in the interpretation of what may be an accurate measurement. When we look at an association, we have to consider whether the results could be due to bias, confounding, or chance (considered in lesson 2 of “Understanding EBM in 4 days”), before we conclude that it is a true association.
In a Swedish study of 1500 children who were followed up over their lifetimes after taking an IQ test, this relationship between childhood IQ and mortality was examined. As with previous studies, they found that increased educational attainment was associated with reduced mortality, with a 9% reduction in men and a 12% reduction in women for each additional year in school. These findings were unchanged after adjustment for the childhood IQ, and so the researchers concluded: “mortality differences among participants by own educational attainment were not explained by childhood IQ, neither for men nor women. Hence, our results do not suggest that differences in early IQ can explain why people with longer education live longer.”
They also found that childhood IQ was independently linked to male adult mortality, and so “higher cognitive ability also seems to have an additional direct protective effect”. In women, the researchers found that the mortality risk was highest in those with the highest childhood IQ, and this risk was greatest in women over the age of 60. They explained this finding as follows: “intelligent women may have a greater underlying risk of dying that is masked by their having on average a longer education and, supposedly, a lower mortality risk than women who spent less time in education”. These findings make the first hypothesis for a direct effect of childhood IQ on health implausible, and it seems much more likely that “the link between IQ and mortality involves the social and physical environment rather than simply being a marker of a healthy body to begin with”.
New doubts about Tamiflu and the real truth
Tonight channel 4 news and the BMJ have released a major story on the effects of Tamiflu. This is a must read as this is the second major systematic review to appear in the BMJ investigating the evidence underpinning "neuraminidase inhibitors" (the class of drugs including Tamiflu) for preventing and treating influenza in healthy adults.
Jefferson and his colleagues should be commended for systematically searching for the truth, and asking, what are the exact benefits and harms of Tamiflu and similar drugs? They are being used liberally in the current H1N1 pandemic and it is important that these types of studies – systematic reviews - are undertaken and independently funded by national bodies to ensure impartiality.
These results are not surprising, in that the benefits of neuraminidase inhibitors are modest, which most clinicians probably already knew. However, amongst policy makers and the wider public this message does not seem to be getting through. Significantly, this paper differs from previous published studies in that the investigators attempted to systematically investigate the potential harms of the drugs. What is disturbing is that only one study explicitly examined drug safety. This is an important omission given the widespread use of Tamiflu.
Moreover, we now know that the evidence-base for a reduction of serious complications such as pneumonia is uncertain. Simply this means the benefits of the drug may be outweighed by the complications, i.e. Tamiflu could cause more cases of pneumonia than it prevents, from what we now know.
What happened next in this study proves pretty shocking. To get key access to the data the BMJ and channel 4 news undertook their own investigation. It is unclear which drafts the Roche investigators saw,and we don't know who authored the papers. One major author named on the abstract of one of the most influential studies told the BMJ he had not even been involved in the study. Yet, we continue to be bombarded with news stories of apparent benefits of antivirals; whilst now knowing that major data are being withheld and manipulated to propagate the unwarranted use of these drugs.
The BMJ commissioned Freemantle to pass judgement on the observational studies. Freemantle rightly states that randomised trials rarely include people with "co-morbidities" (other health problems), as adverse events in these groups may be significantly worse. Therefore, this undermines attempts to establish the safety of the new drug. To be able to generalize results to the wider population what we require is observational data of the safety profile in routine practice. That is real life patients who are excluded from the trials for the reasons outlined above.
There is a pressing need to understand the benefits and potential adverse effects of these drugs as the current evidence base supporting their use is now so uncertain. In individuals with mild symptoms their use should be discontinued with immediate effect. Using antivirals liberally runs the risk of generating resistance. We have known this for many years. More worryingly in those at high risk the benefits remain uncertain and their use has to be considered by clinicians on a case-by-case basis. Experts and those that generate policy should look at these documents carefully and stick to the evidence.
Overall the benefits of these drugs are fairly limited. Tamiflu provides only a small benefit by shortening the duration of illness in children with influenza and has little effect on asthma exacerbations or the use of antibiotics. Its effects on the incidence of serious complications and on the current A/H1N1 influenza strain in both adults and children is unknown.
How to communicate risk: part 2 expression of risk needs improving
In the first article in this series we looked at the dimension of risk. Expression of risk in terms of an unwanted outcome or event can be described with descriptions or distinctions based on both its quality or on its quantity. The probability can be described in qualitative terms such as rare or infrequent or expressed quantitatively such as 1 in 1000. What is important to acknowledge that patients differ in what they like.
For example, in the context of a study on an invasive diagnostic procedure, 467 patients varied in terms of the way the risk was told to them: 43 % preferred qualitative (verbal expressions) disclosure of information vs. 36% preferring quantitative. The exact number varies form study to study, but roughly it is about half and half for each type of disclosure. In terms of influenza vaccines for children, slightly more parents preferred quantitative information (60%). It is often interesting how we come to decisions without knowing the basic quantitative risk. For instance, ask yourself the question: What is the risk of death from swine flu compared to seasonal flu? Qualitative descriptions are often foremost in our minds and very few will be able to give quantitative information. To be honest, I think I’ve shot myself in the foot as I don’t know the answer to this question myself. But, my premise is correct, as words like rare and infrequent are what come to my mind.
The most useful strategy identified in a systematic review of effective formats for communicating probabilistic information, including 15 randomized controlled trials found for both written and verbal information, patients have a more accurate perception of risk if probabilistic information is presented as numbers rather than words. That means that it is all right to say words like rare or infrequent but without a quantitative number such as 1 in a million people find it difficult to correctly perceive the actual probability.
How to present qualitative information
Qualitative descriptions are appealing because they use common words that seem to be generally well understood. However, qualitative words, of which there are many, have no generally accepted anchoring at specific quantitative levels of frequency, despite efforts to promote such anchoring.
Data about actions sometimes bear little relation to the statistics. Saxe found no connection between the probabilities provided to couples during genetic counselling and the decisions they made. The use of verbal categories with scales of risk, such as very unlikely, was easier to use and represented better their true feelings.
Proposals have been made to standardise the language of risk with standardised terms for specified frequencies ("high" for risks 1 in less than 100 and "moderate" for between 1 in 100 and 1 in 1000). However, it’s all in the interpretation and patients would probably not understand such standardised terms consistently.
There are a number of simple recommendations worth incorporating based on this article:
In describing risk choose either:
1) numeric probabilities, or
2) numeric and qualitative information together
Qualitative descriptions should use common words that seem to be generally understood.
Next time you are met with a risk, whether presenting or reading about another scare story in the media, you might want to consider whether some of these issues outlined have been met. They probably won’t have.
When politics is bad for your health: AIDS in South Africa.
South Africa, with a population of 50 million, has nearly 6 million people infected with HIV — more than any other country in the world. AIDS-related diseases kill nearly 1,000 South Africans every day.
Antiretroviral therapy (ART) has been available since the late 1980s, but even in 2009, ART is not available to many people with HIV/AIDS in poorer countries. Since the beginning of the epidemic, South Africa has been the hotbed for political activism and human rights campaigns to address the massive inequalities in AIDS management in the developing world. For example, the Treatment Action Campaign (TAC), led by Zackie Achmat, successfully sued the Ministry of Health in South Africa in 2002 to ensure access to ART for HIV-infected pregnant mothers, so that mother-to-child transmission was reduced. The TAC even took Merck and other pharma companies to court to force them to make their patents available to generic drug-producing companies so that cheaper antiretroviral drugs could be available in South Africa. This type of action massively forced the price of ART down in the last decade, and meant that generic companies are the main suppliers of ART in this country, and across Africa.
In the past, the relationship between politicians and the public health community of South Africa, particularly relating to HIV/AIDS, has been confrontational at worst, and lukewarm at best. Past President, Thabo Mbeki, famously denied the association between HIV and AIDS and instead focused mainly on poverty as a powerful co-factor in AIDS diagnosis. His successor, the current President Jacob Zuma, went on trial in 2006 for allegedly raping an HIV-positive woman. He earned wide criticism and incredulity when he admitted that he had unprotected sex and stated his belief that showering after sex would prevent HIV transmission. We do not need a clearer illustration of what happens when ill-informed politics and lay beliefs inform health policy and practice, instead of science and evidence. More than 330,000 lives were lost to HIV/AIDS in South Africa from 2000 and 2005, due to the policies of the South African government. In the UK and most countries of the world, we have similar instances of ill-informed health policy based on beliefs or poorly interpreted evidence, which have led to negative impact on health. For example, the Lancet publication of a case series of only 12 patients with autism led to greatly reduced uptake of the MMR vaccine in the UK with far-reaching consequences, even though the research was discredited years later.
Thankfully, a new era is being heralded in South Africa with a huge shift in direction in terms of HIV/AIDS policy. This week’s Lancet describes President Zuma’s change of heart, leading his country with the slogan, “I am responsible, we are responsible, South Africa is taking responsibility”. Unsurprisingly, the story has not received much coverage in the world press, but the message is clear. Good health policy must rest on good evidence and government action to the contrary is irresponsible and often bad for the health of the population.
Medicine and media - do they have to be awkward bedfellows?
My Monday evening was spent at an event organised by the London Business School' Healthcare Club, called "Challenging the Status Quo". Andrew Witty, CEO of GlaxoSmithkline, spoke passionately about why drug development and profits do not have to be at the expense of access to medicines in poor countries. His company has been the first global pharmaceutical company to pledge to pool its patents to allow generic manufacture of its drugs in poor countries, and to enforce differential pricing between rich and poor countries. The take home message was that it is possible to change the prevailing practice or norms, even in an industry like pharma.
Sanjay Gupta is a neurosurgeon with a difference and he is changing the norms in a totally different arena. He is most famous for being CNN's chief medical correspondent and his TV programmes and writings are hugely popular in the US for their new angles on healthcare problems around the world. For example, he has followed medics in war zones, and was filmed meeting the Mexican boy, who was thought to be the index case of swine flu, amid global hysteria about the disease. He recently turned down the job to be Surgeon-General in President Obama's staff.
Gupta made two important points. Firstly peer review, the process used by journals to accept and then publish scientific articles, takes too long and is too slow at delivering up-to-date information for mass consumption. Moreover, one study showed that "... although recommendations made by reviewers have considerable influence on the fate of both papers submitted to journals and abstracts submitted to conferences, agreement between reviewers ... was little greater than would be expected by chance alone". In other words, peer review is far from perfect. Therefore, many people (including health professionals) are increasingly gaining their knowledge from alternative sources such as the internet, blogs and Twitter. Secondly, the pressure for news headlines from mass media corporations does not necessarily have to conflict with the need for good quality, science and health information. There is a plethora of health-related news and advice and so there is plenty of room for health professionals to work innovatively with new media to ensure quality of that information. We wholeheartedly agree at trusttheevidence.net. Are you thinking enough about where you get your up-to-date health information from?