taking stock rammya mathew why we must …...health secretary, matt hancock, said johnson would end...

Men and women enjoy vastly different levels of financial reward in their jobs. It’s particularly difficult to explain in medicine, which is, by and large, a career with a well

defined trajectory and non-negotiable pay scales. Trying to unpick this is not straightforward. At first

glance it seems to be down to fewer women being in leadership positions: isn’t it scandalous that 77% of the NHS workforce are now female, yet they hold only 37% of senior jobs?

Are women less excellent? Are they inherently bad at leadership? Or can these depressing statistics be explained by age old societal norms, which place the responsibility for caring on women, giving men more freedom to pursue their careers? We know that women with children are subject to a “motherhood penalty”—experiencing a “per child” wage penalty and being perceived as less competent at their jobs— often meaning that there’s little hope of them ever recovering their true earning potential.

The BMA has secured enhanced occupational pay for shared parental leave, which is a step in the right direction, as it ensures that families are not financially disadvantaged for making a choice that promotes equality in both parenting and the workplace.

But many women, and indeed many men, believe that parenting is an important part of their identity, proactively choosing to change their work schedules to align better with parenting responsibilities. Unfortunately, part time or flexible working is still mostly seen as incompatible with the challenges of senior leadership—and this is where we need to challenge the status quo. It’s not acceptable that more than half of the workforce are deemed ineligible for a post because of gender or the fact that they often have more caring responsibilities.

Organisations need to think creatively about how to support part time and flexible working, how to

help people into job shares, and how to get the very best out of their employees by retaining a happy, healthy, and productive workforce. Recognising organisations that are doing their bit to support women in leadership, and affording them a platform to demonstrate the benefits of doing so, will hopefully help to reverse the current situation where women are systematically under-represented at the top. Supporting women in leadership matters. It’s the right thing to do if we aspire to be a fair and inclusive society that values people for their skills and expertise.

As Michele Bachelet, former executive director of UN Women, puts it, “The strength, industry and wisdom of women remain humanity’s greatest untapped resource. We simply cannot afford to wait another 100 years to unlock this potential.”Rammya Mathew is a GP in London [email protected] this as: BMJ 2019;366:l4550

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the bmj | 13 July 2019 63

It’s not acceptable that more than half of the workforce are deemed ineligible for a post because of gender

TAKING STOCK Rammya Mathew

Why we must support women in leadership

“The flavour of media stories on the waiting times app was misleading” DAVID OLIVER “I’ve learnt about the unpredictability of medicine” HELEN SALISBURY PLUS Getting to know your patient; in whose hands is the NHS safe?

64 13 July 2019 | the bmj

The Tories are again holding their regular festival of anointing a new leader for the party to destroy over the issue of Europe. Boris Johnson enjoys immense advantages, but it would be unwise to rule out Jeremy Hunt, with recent opinion polls of the general public showing Hunt moving to lead position.

But the next prime minister is chosen only by the members of the Conservative Party. A YouGov poll of Tory members found they would rather see the UK economy wrecked, the union with Scotland and Northern Ireland ended (despite their party’s name), and the Conservative and Unionist Party itself destroyed rather than see Brexit not happen.

This suggests that, if party members vote on Brexit alone rather than on ability to win a general election, they might be willing to look past Hunt campaigning for Remain in the referendum if they believe that he is better placed to get Brexit to happen.

By no coincidence whatsoever, this has been the central theme of Hunt’s campaign. His case for being leader is that he would be the more competent and the better negotiator of a revised deal with the EU (which the EU has repeatedly stated isn’t going to happen). He has also set out his detailed plan for a no deal Brexit. The competence argument may persuade party members.

The NHS and social care have not come up much in the campaigns. When the current health secretary, Matt Hancock, said Johnson would end public sector pay restraints, Johnson refused to endorse the promise, telling the BBC, “You need a dynamic market

economy to pay for fantastic public services and infrastructure. And you need fantastic public services and infrastructure, great NHS, great education, to enable business to have the confidence to invest.”

Hunt raised the infamous “£350m” bus slogan in a TV interview, saying that although Johnson promised both £350m a week and Brexit, he had actually delivered extra money for the NHS and would deliver Brexit.

There has been more detail on social care, with Hunt telling party members that he wants reform of the system to be the party’s next “social mission.” Johnson has suggested investing more. And in the BBC’s televised

Last week, Boris Johnson suggested that a good way to revamp politics after-Brexit would be to base “tax policy on clear evidence.”He was referring to what he

describes as “stealth sin taxes”—taxes on unhealthy foods and drinks currently exemplified by the soft drink industry levy—and pledged a review into their effectiveness.

Aside from any of the potential politics or conflicts of interest underlying these claims, sugary drink taxes are an important piece of evidence based public health policy.

We all know there’s an obesity crisis—a third of 10-11 year olds and two thirds of adults in England are overweight or obese, at an estimated cost to the NHS of £6bn in 2014. Crudely speaking, weight gain is caused by eating too much and moving too little, but these are heavily influenced by our social, environmental, and economic conditions, not to mention the interplay between these and our genetics, and physical and mental health. It’s a multifaceted problem that needs a multifaceted solution, and evidence suggests a soft drink tax should be a key part.

So why target just soft drinks? For a start,

nearly all of us eat too much sugar, with drinks playing a key role, particularly among children. Teenagers eat nearly three times their recommended amount of free sugar—any added sugar, plus sugar in juice or syrup—of which over a fifth comes from soft drinks.

No nutritional benefitSoft drinks are also associated with a range of poor health outcomes with no nutritional benefit. Randomised controlled trials show how they can lead to weight gain, and there are rising numbers of studies associating them with diabetes, tooth decay, heart disease, and hypertension. On top of this, the drinks people switch to are generally healthier.

Taxes are often used to correct “negative externalities”—the consequences of products that aren’t borne in the original price but which a tax then “internalises.” For example, tobacco taxes don’t just change behaviour, they internalise the health and societal costs of heart disease and cancers. The same can be said of soft drink taxes and obesity.

Over 30 countries have implemented some sort of soft drink tax, and “real world” data showing their effects on consumers are

accumulating. Mexico has been particularly well studied with their peso per itre tax—a price increase of around 10%—resulting in an 8% reduction in purchases over the first two years. More recently, data from Philadelphia’s 1.5 cents per ounce tax showed a 40% reduction in sales and a meta-analysis of soft drink tax evaluations published last month found that, on average, purchases are reduced by around 10% for a 10% price increase.

One of Johnson’s main concerns was if these taxes “unduly hit those on lower incomes.” Here he has a point, soft drink taxes—like National Insurance, VAT, and tobacco taxes—are regressive: people with less money pay a higher proportion of income. But evidence from a 2016 systematic review, and from more recent Mexican data, suggest greater levels of behaviour change and thus greater health benefits among lower socioeconomic groups.

Furthermore, population level interventions requiring lower levels of agency—like taxes—are more effective and more equitable

PERSONAL VIEW Adam Briggs

“Sin taxes”—the language is wrong but the evidence is clearBoris Johnson has pledged to review the sugar levy on fizzy drinks if he becomes PM, but all that would prove is that the policy is right

OBSERVATIONS Andy Cowper

The NHS and our next prime minister

Rising numbers of studies associate fizzy drinks with diabetes, tooth decay, heart disease, and hypertension


ACUTE PERSPECTIVE David Oliver

Can apps relieve pressure on emergency departments?

The recent announcement of a new “NHS waiting time app” prompted media headlines, with claims that it could “help patients find

hospitals with the shortest A&E queue.”The context makes this a compelling

story. Performance against emergency departments’ waiting time goals has declined, with targets serially missed. Bed occupancy in our acute hospitals is hovering around 90%. Media stories describe overcrowded departments, long trolley waits, and ambulances stacked outside. NHS England is piloting some new waiting time metrics.

Reading past the headlines, the story concerns the “WaitLess” app currently in use in Kent. The app, which uses data from SHREWD (Single Health Resilience Early Warning Database), allows patients to book GP appointments and order prescriptions. Users can compare waiting times in local emergency departments or minor injury units in real time, to pick one with a shorter wait. On the face of it this may look like a win-win for patients and stretched departments, allowing people with a minor injury or illness to be assessed away from their main acute hospital.

NHS England, which advertises the app for use in Northamptonshire and Dorset, plans to extend it to other regions alongside more urgent walk-in treatment centres, extended GP opening times, and greater use of NHS 111.

What hasn’t been reported much is an

independent evaluation of the WaitLess app carried out in east Kent by the University of Greenwich. This showed a 5% reduction in the number of people using levels 3 and 4 emergency departments and an 11% increase in the number with minor injuries or illnesses using urgent treatment centres. But Kent has a range of those types of units, in close proximity. Things won’t be so easy if the nearest is miles away and only one local hospital emergency department is within reasonable travelling range.

The flavour of the media stories was misleading, as we’d still want anyone with a genuine emergency to go to the nearest acute hospital emergency department as soon as possible. Even for patients with several hospitals fairly close, travel time would have to be factored in, and a small shift towards a unit with a shorter wait time would soon overwhelm that department too. Perhaps some users of walk-in treatment centres could have been supported perfectly well non-urgently, rather than by “unit shopping.”

While I realise the appeal of Tomorrow’s World-type stories, it would be good to see some realism, caution, and tempered expectations below the headlines, the endorsements by an enthused health secretary, and unsubstantiated claims by the Taxpayers’ Alliance that the app

would “save lives.”David Oliver is a consultant in geriatrics

and acute general medicine, Berkshire [email protected]

Cite this as: BMJ 2019;366:l4495

A unit with a shorter wait time could soon be overwhelmed

OBSERVATIONS Andy Cowper

hustings of the original group of candidates—minus Johnson—the consensus was that more resources were needed.

Although many junior doctors will disagree, Hunt matured as a politician in his time as health secretary, as seen in his time as foreign secretary. Johnson’s

underwhelming tenure as foreign secretary was capped by taking three days to resign over Theresa May’s withdrawal agreement.

Predicting anything in politics is hazardous, but of these two candidates Hunt is the one demonstrably more suited to the intense and wide ranging job of prime minister.Andy Cowper, editor, Health Policy Insight [email protected] this as: BMJ 2019;366:l4554

than interventions targeting individuals, such as gym or cookery classes. But irrespective of these arguments, rather than scrapping a regressive tax aimed at improving population health, why not simply make the remaining tax system proportionately more progressive?

Public supportPerhaps we needn’t be concerned at Johnson’s pledge. Soft drink taxes have public support. Last week a YouGov poll reported an approval rating of 55% for taxes on unhealthy food or drink, including 54% among Conservatives.

Note that the poll referred to taxes on unhealthy products, not “sin taxes.” There is nothing immoral about consuming soft drinks. What might be immoral is stigmatising people who are overweight as sinners while not supporting us all to stay healthy against a tide of environmental triggers.

So, in a week when the news is led by stories that obesity now causes more cancers than smoking for four subtypes, we should get behind basing tax policy on clear evidence.

Adam Briggs is a public health specialty registar, Health Foundation, and is an academic visitor at the University of Oxford [email protected] this as: BMJ 2019;366:l4616

Doctors spend a lot of time explaining things to patients: not just what might be wrong, but why it might have happened

and how we can investigate and treat it. But the flow of information isn’t just one way, and I’m grateful to my patients for the many things they’ve taught me.

Some are fairly simple, such as the time it really takes to recover from musculoskeletal injury, which is usually longer than the optimistic predictions in emergency departments. This is very useful when it comes to reassuring subsequent patients that the fact that their shoulder still isn’t better at three months isn’t abnormal and that they can still expect a full recovery.

Sometimes it’s more a question of being reminded of what’s possible. I know about the power of changing habits to improve health, but when I meet the patient whose life is transformed by taking up running, or the man who no longer has type 2 diabetes after losing weight, the theoretical becomes actual. When counselling others I can do so with conviction, with these patients in my mind’s eye.

I ask patients to “tell me what happened when you went up to the hospital,” not only to convey interest and empathy but as a genuine inquiry, as I may learn useful facts. It’s easy to get rusty in primary care, and my knowledge of the latest hospital innovations may be

technical rather than practical, learnt from journals and update courses and lacking important details. I could turn to the internet, but it’s often more useful to ask a patient what actually happens. I want to explain to the next patient what to expect, and what better source of a patient centred explanation can there be?

More than anything else, I’ve learnt about the unpredictability of medicine and the wide variety of reactions to it, both physiological and psychological. Much as patients like certainty, it’s also useful to be able to outline, for example, the range of recovery times or the likelihood of side effects from medicines. I can sometimes find numbers and evidence, but mostly patients ask, “What have you seen in another patient like me?”

Possibly the most important thing I’ve learnt—but I often need to remind myself—is that people have reasons for their actions that I can’t guess and won’t know unless I ask. Fears that may seem irrational turn out to be completely understandable when I explore the family history. Self neglect isn’t so odd when you know of the intensity of caring responsibilities your patient has for others. And, when I do ask, I often learn about the reality of lives much harder

than my own and the remarkable resilience of my patients.

Helen Salisbury is a GP in Oxford [email protected]



Catch up on all of The BMJ’s latest podcasts at bmj.com/podcasts

Fears that may seem irrational turn out to be completely understandable when I explore the family history

After GrenfellTwo years on from the Grenfell Tower fire, Anu Mitra, a consultant emergency physician who was working at the closest hospital that night, talks about the tragedy:“The people who were brought in were in extreme psychological distress. Some couldn’t speak because of the shock. In contrast, there were also people who felt that they just needed to tell someone what they’d seen. They needed to bear witness because in the chaos and the rescue they hadn’t had a chance to talk to another human being. And those first human beings who spoke to them, in many cases, were nurses and the doctors. So we were hearing first hand accounts of horrific experiences. And that's quite something to bear on our shoulders.”Listen to the podcast in full to hear about what his hospital has learnt about supporting staff in the wake of mass disasters.

The NHS and whistleblowersThe BMJ talks to Margaret Heffernan, a chief executive and writer who has “interviewed hundreds of whistleblowers in all walks of life.” She talks about how culture and groupthink can lead to situations where whistleblowers are ignored, and observes that she has “never encountered an organisation as vicious in its treatment of whistleblowers as the NHS.” Here she discusses that treatment:“When people start asking questions that nobody asked for, very often they are shunned or interpreted as troublemakers or cranks or pushy. But what I’ve discovered is that whistleblowers start off as your most dedicated employees. It’s really important to recognise that, overwhelmingly, people who raise concerns are doing so out of loyalty, out of integrity, and a real desire to make an organisation they love even better.”

PRIMARY COLOUR Helen Salisbury

Patients are the best teachersLATEST PODCAST

Edited by Kelly Brendel, deputy digital content editor, The BMJ


Medicines regulators around the world are pursuing a strategy aimed at accelerating the

development and approval of drugs.1 2 These approaches are based on the assumption that faster access to new drugs benefits patients. The rhetoric of novelty and innovation creates an assumption that new products are better than existing ones.

But although gaps in the therapeutic armamentarium undoubtedly exist, research covering drug approvals since the 1970s suggests only a limited number of new drugs provide real advances over existing drugs.3‑9 Most studies put the proportion of true innovation at under 15%, with no clear improvement over time.

No evidence of added benefit for most new drugsBy law, the German health technology assessment agency IQWiG (Institute for Quality and Efficiency in Health Care) must investigate the added benefit of new drugs compared with standard care. The classification of added benefit—as minor, considerable, or major—depends on the importance of the outcome and magnitude of the treatment effect, and the information affects pricing and treatment decisions (box).

Between 2011 and 2017, IQWiG assessed 216 drugs entering the German market following regulatory approval—152 new molecular entities and 64 drugs granted a new indication. Almost all of these drugs were approved by the European Medicines Agency for use throughout Europe. Thus our results also reflect the outcome of European drug development processes and policies.

Only 54 of the 216 assessed drugs (25%) were judged to have a considerable or major added benefit. In 35 (16%), the added benefit was either minor or could not be quantified. For 125 drugs (58%), the available evidence did not prove an added benefit over standard care for mortality, morbidity, or health related quality of life in the approved patient population (fig 1). As the effects of drugs often vary between patients, there might be subpopulations

benefiting despite no relevant effects in overall study populations. However, IQWiG already considers subgroups by age, sex, disease severity, and further disease specific factors. Of the 89 drugs with an added benefit, 52 (58%) showed an added benefit in the whole approved patient population, and 37 (42%) had an added benefit in only part of the approved patient population.

The situation is particularly egregious in some specialties. For example, in psychiatry/neurology and diabetes, added benefit was shown in just 6% (1/18) and 17% (4/24) of assessments, respectively (fig 2, p 69). Presumably, this is because regulators still allow placebo controlled studies even though health technology assessment bodies have long recommended active controlled trials, which provide more useful information.13‑15Figure 2 also shows that drug development and approval do not cover the various indications equally, with oncology drugs by far the most numerous.

What does this mean for drugs available in Europe? Only two drugs (1%) were shown to provide less benefit than standard care, but for 125 we mostly lack the data to say one way or the other. For 64 of these drugs, no studies were available comparing the new drug with standard care. For another 42 drugs, although studies have compared the drug to an active comparator, the comparator was inappropriate—for example, because of off‑label drug use or inappropriate dosing regimens. The remaining 19 drugs were tested against an appropriate comparison (standard care) but did not show an advantage (or clear disadvantage) of the new drug.

Illusion of post-approval evidenceSome people have argued that limited information at the time of regulatory approval (and thus widespread use by patients) is the price to be paid for early access to innovative drugs. This argument suggests that research conducted after market entry will ultimately prove the benefit for patients.16

The reality, however, looks quite different. For instance, a systematic

KEY MESSAGES

• More than half of new drugs in Germany lack proof of added benefit over existing treatments

• To increase innovation manufacturers should be required to submit comparative data at the point of drug approval

• Payers could then set reimbursement and pricing at levels that reward relevant outcomes for patients

• Combined action at EU and national levels is required to revise the legal and regulatory framework, introduce new drug development models, and focus on the needs of patients

ANALYSIS

New drugs: why are so few shown to add benefit?International drug development processes and policies are responsible and must be reformed, argue Beate Wieseler and colleagues


evaluation of cancer drugs approved by the EMA between 2009 and 2013 showed that most had been approved with no evidence of clinically meaningful benefit on patient relevant outcomes (survival and quality of life), and several years later the situation had little changed.17 Perhaps more troubling, a systematic review of new drugs for over 100 indications approved by the US Food and Drug Administration on the basis of limited evidence found that superior efficacy on clinical outcomes was confirmed in less than 10% of cases.18

Despite their promise, a critical and well known problem with post‑marketing studies is they often do not happen. Analyses have found that only about half were completed on time20 or within five to six years.21 The situation in Germany is similar: none of the six post‑approval studies that were due for reassessment between 2011 and 2017 were conducted. Globally, regulators do little to sanction non‑compliant companies.

Me-too drugsAlthough the term “me‑too drugs” is heard less frequently today, several new drugs with an added benefit in oncology and infectious diseases have the same mode of action, indicating that a commercially successful drug with a new mode of action is often followed by several similar drugs. For instance, the IQWiG analysis showed

that in Germany 12 of 48 successful assessments (25%) in oncology were for PD‑1 or PD‑L1 inhibitors. The various drugs that showed added benefit in hepatitis C all use one of the three types of direct antiviral action or a combination thereof.

Analyses of drug development pipelines show a similar pattern. An international review of ongoing and planned trials in immuno‑oncology identified large numbers of trials investigating drugs aimed at the same targets, including even more PD‑1 and PD‑L1 inhibitors.22 These findings not only raise doubts about the efficiency of the drug development process but also about whether the current trial landscape is hampering the productive development of new treatment options by enrolling large numbers of patients in trials providing at best me‑too drugs, wasting money on redundant developments, and failing to develop new approaches with different mechanisms of action aiming at broader patient populations.

In addition, it has been shown that the newer genome driven cancer therapies, which form an important part of the drugs showing added benefit in our assessments, provide an added benefit for only a minority of patients with advanced cancer.24 For the overall patient population, the current output of drug development may thus be resulting in even less progress than our assessments suggest.

Effect on patients and healthcare systemsClinicians and patients deserve impartial and complete information on what to expect from a certain treatment, including information on the benefit of alternative treatments or no treatment. But given the current information gaps this is not possible. As a consequence, patients’ ability to make informed treatment decisions consonant with their preferences might be compromised,25 and any healthcare system hoping to call itself “patient centred” is falling short of its ethical obligations.26 27

The information gaps also harm healthcare systems. High levels of uncertainty about treatment benefit jeopardise quality care and impede

Early assessment of benefit of new drugs in GermanyOn 1 January 2011, Germany introduced early benefit assessment (Frühe Nutzenbewertung) of new drugs to determine whether a new drug has any added benefit over standard care. The Federal Joint Committee (G-BA), the main decision making body within the German statutory health insurance system, is responsible for the assessment procedure and ultimately decides on the added benefit.

The added benefit of the new drug is primarily determined by a direct or a suitable indirect comparison with standard care using the outcomes of mortality, morbidity (including adverse events), or health related quality of life.ProcedureWhen a newly approved drug enters the German market, the drug company responsible must submit a standardised dossier containing all available evidence of the drug’s added benefit over standard care to the G-BA. The G-BA generally commissions IQWiG to assess the evidence contained in the dossier within three months after market entry. After publication of IQWiG’s assessment report, the G-BA conducts a commenting procedure and hearing, during which the drug company and other specified parties may submit comments. After evaluation of these comments, the G-BA issues a decision on the probability and extent of added benefit. The final decisions therefore sometimes differ from IQWiG’s assessment.

Minor 20

Considerable 32

Non-quantifiable 15

No proof of added benefit 125

Less benefit 2

Major 22

Fig 1 | IQWiG’s assessment of added benefit for 216 new drugs entering the market in Germany, 2011-17 (Maximum added benefit in any patient group included in a given assessment. Proof requires a statistically significant benefit on patient relevant outcomes in a randomised controlled trial or very large benefit in a non-randomised trial)


decision making, particularly on highly priced drugs in economically strained situations.

A new approachSince drug development, approval, reimbursement, and pricing are highly regulated, the current state of affairs suggests a policy failure. We need new approaches.

We believe that regulators should become far less tolerant of shortened drug development programmes. Restoring their previous policy, they should demand robust evidence from longer term and sufficiently large phase III randomised controlled trials to prove efficacy and safety, which in parallel could be used to collect data for health technology assessment. Current regulatory laws support this suggestion. In addition, given the influence of regulatory decision making on wider healthcare systems, the specification of regulatory approaches should involve all parties responsible for ensuring appropriate healthcare.

Information gaps could be closed further by a mandatory requirement to conduct active controlled trials—if not for approval, then for better understanding of a drug’s benefit in the health technology assessment process and in clinical practice. The current initiative on legislation for health technology assessment in Europe is an opportunity to implement such requirements28 and could improve the information available on new drugs.

In parallel, reimbursement and pricing decisions should avoid incentivising marginal outcomes for patients29 30 or outcomes based on highly uncertain evidence, but rather reward the achievement of relevant outcomes. Initial steps for defining relevant outcomes have already been undertaken; both the American and the European societies of oncologists have developed evaluation frameworks to grade the benefit of treatments and distinguish marginal from relevant outcomes.31 32 These frameworks could be a starting point for the discussion and extended to other indications. Patient involvement in these discussions is essential.33 The discussion on relevant outcomes should also feed back into the discussion on regulatory decision making.

In the longer term, health policy makers need to take a more proactive approach. Rather than waiting for drug companies to decide what to develop, they could define the health system’s needs and implement measures to ensure the development of the treatments required. Initiatives for the development of new antibiotics are first examples of such approaches, including one coordinated by the World Health Organization, in which it identifies priority pathogens, reviews development pipelines, and designs and conducts clinical trials in collaboration with commercial and non‑commercial partners.34 A general review of drug development pipelines on a European level taking account

of current and expected burden of disease would be a first step to enable policy makers to react to research gaps and realign drug development with public health needs.

Furthermore, new models of drug development might represent an important part of the solution. The drug development model of the Drugs for Neglected Diseases initiative (DNDi) is based on needs driven, disease‑specific target product profiles. The model also ensures access to new treatments and to knowledge. It is built on the financial and scientific independence of DNDi and on collaboration between public and private partners.35 A project conducted by the Belgian and Dutch health technology assessment agencies on possible future scenarios for drug development has suggested needs oriented public‑private partnerships and not‑for‑profit drug development as well as new models for the pharmaceutical industry such as “pay for patents” or drug development as a public enterprise.36

Another suggestion to improve the efficiency, quality, and relevance of drug development is to use an open source model.37 The potential advantages of an open source model, have recently been shown in a project on Alzheimer’s disease that has been restricted to regulators but could be expanded to other parties.38

Targeted healthcare policy informed by evidenceThe setting of healthcare policy goals is highly politicised. Nevertheless, drug policy should be based on specific public health goals.

Combined action at EU and national levels is required to define public health goals and to revise the legal and regulatory framework, including introducing new drug development models, to meet these goals and focus on what should be the main priority in healthcare: the needs of patients.Beate Wieseler, head of department of drug assessment [email protected] McGauran, researcherThomas Kaiser, head of department of drug assessment, Institute for Quality and Efficiency in Health Care, Cologne, GermanyCite this as: BMJ 2019;366:l4340

Restoring their previous policy, regulators should demand robust evidence

Perce

ntage

Oncology(n=82)

No proof of added benefit

Less benefit

Non-quantifiable

Minor

Considerable

Major

Infectiousdiseases(n=29)

Diabetes(n=24)

Cardiovascular/pulmonary

(n=20)

Psychiatry/neurology

(n=18)

Otherindications

(n=43)

0

40

60

100

80

20

Fig 2 | Results of the assessment of added benefit versus standard care by indication for drugs entering the German market, 2011-17


Trust before mandates

In 2011, the US Supreme Court determined that vaccines are “unavoidably unsafe.” Where there is risk, no matter how small, there must be choice. I understand the public health concern, but the UK has many other ways to increase vaccination uptake, such as education and outreach, before resorting to mandates.

Mandatory vaccinations are likely to be unacceptable to a small but important core group of society and would only foster greater distrust of the medical establishment and government. It could disproportionately harm children in lower socioeconomic classes, who are the most vulnerable, should they be barred from school because parents refuse to comply but lack the resources to move.

Rather than resorting to compulsion, we need to provide better information and encourage trust in vaccines. A better system and an open log to monitor adverse events would be the best way to show parents that vaccines are safe.Melissa So, corporate finance director, London


Flaws in the herd immunity model

Draeger mentions herd immunity in support of compulsory measles vaccination (Head to Head, 8 June).

The concept of herd immunity arises from ordinary differential equation models, which assume that children in rural Scotland or Wales have the same chance of contact with an infected person in London as do children in Westminster.

In scale-free contact networks, only universal coverage with full efficiency

leads to eradication. Calculating the true protective threshold requires perfect knowledge of every person’s contacts but is likely to be higher than the figures routinely quoted.

Case isolation and quarantining contacts are effective, especially if combined with rapid ring immunisation. So investing in effective surveillance with well resourced local outbreak control teams is a better strategy. It worked before but takes decades.

Meanwhile, all parents should be encouraged to protect their own children by participating in the full immunisation schedule.Mark Temple, retired public health physician, PenarthCite this as: BMJ 2019;366:l4472

VACCINE HESITANCY

Misinformation on social mediaAs the number of people hesitant to engage with vaccinations grows, the world seems to be fighting fire with fire, suggesting that we ban unvaccinated children from school and make vaccination compulsory (Editor’s Choice, 8 June).

People who oppose vaccination are not ignorant; they have legitimate questions but do not have access to the information they need. They have unlimited access to social media outlets that spread misinformation. Pushing these people away just makes it easier for these outlets to pull them closer.

A poster in general practice is all well and good, but is it just preaching to the choir? Health promotion needs a booster shot; the message needs to be in the same place as the opposition. The NHS Facebook page gets between 15 and 150 “shares” per post—considering that half of all parents with small children have been exposed to misinformation about vaccines on social media, we could be doing better.Jack J Broadbent, 4th year medical student, LondonCite this as: BMJ 2019;366:l4457

LETTER OF THE WEEK

Compulsory vaccination would exacerbate scepticismVaccination programmes reflect the solidarity principle on which the foundations of living in a community are based. If vaccination is needed to protect collective health, then being part of a community should be enough to make everyone accept it. Why, then, make it compulsory (Head to Head, 8 June)? Maybe the expression “There is no such thing as society, there are only individuals” has made us forget that our personal freedoms might impinge on those of others.

The NHS is a powerful tool for implementing prevention programmes, but the last economic crisis undermined its sustainability and reduced health spending. A society that aims to recover its founding values should invest in the expansion of health promotion policies and should confine the obligation to emergencies, because in the medium to long term compulsory solutions exacerbate resistance and scepticism.

Denying the importance of adverse events, which are sporadically associated with vaccination, fuels the anti-vaccination movement. Although the adverse events reported are often lacking scientific importance, they are the expression of the suffering experienced by a child and their family who, feeling part of a community, accepted prophylaxis against a collective relapse.

Self respecting societies should leave the question of whether an injury comes from a vaccine to scientists and should ensure financial and social support—as no fault compensation schemes—to those who have shown that they understand what being part of a community means.Giuseppe Vetrugno, risk manager and forensic pathologist; Michela Cicconi, forensic pathologist and trainee in public health; Federica Foti, trainee in forensic medicine; Angelico Spagnolo, forensic pathologist; Fabio De-Giorgio, forensic pathologist, RomeCite this as: BMJ 2019;366:l4464

LETTERS Selected from rapid responses on bmj.com

MEASLES

P M

ARAZ

ZI/S

PL

Calculating the true protective threshold requires perfect knowledge of every person’s contacts


VACCINE SURVEILLANCE

Is the HPV vaccine safe?

Chandler discusses the difficulties in the pharmacovigilance of HPV vaccines due to the non-specific nature of dysautonomia symptoms reported to surveillance agencies (Analysis, 8 June).

We found that serious adverse event signals were present in the largest randomised trials of HPV vaccines but were ignored or minimised.

A safe vaccine should not have a biological gradient of adverse events. Nine valent HPV vaccine has more than twice the virus-like particles and aluminium adjuvant as the four valent dose. In the largest HPV vaccine trial, those who received the nine valent dose had more vaccine related systemic adverse events than those receiving the four valent dose (29.5% versus 27.3%, P=0.003) and had more serious systemic adverse events (3.3% versus 2.6%, P=0.01). The authors ignored these crucial statistical differences.

Neuropathic pain and dysautonomia after HPV vaccination has been reported by independent clinicians in different places, circumstances, and times. Implementing the precautionary principle seems appropriate.Manuel Martínez-Lavín, chief of rheumatology, Mexico CityCite this as: BMJ 2019;366:l4508

CLIMATE CHANGE ELEPHANTS

Overpopulation and landscape manipulationOverpopulation is an elephant in the room for climate change (Letters, 8 June), but the medical profession lacks the memory of an elephant.

In the late 1960s a pressure group was set up called “Doctors and Overpopulation.” It published a report in the Ecologist and prophesied many of the problems that are obvious today. Sadly, it was ignored and died. But its original activities were reported in The BMJ.

There is another elephant—landscape manipulation, such as the destruction of tropical rainforests in Brazil and Indonesia, deforestation in the Himalayas, and the

diversion of rivers away from the Aral Sea. These have materially affected the rate of global warming.

I doubt that sufficient action will be taken, but eruption of a supervolcano would not only wipe out populations along many coasts but also create a huge ash cloud that will rapidly cause global cooling. Nature has its checks and balances.Andrew N Bamji, retired consultant rheumatologist, RyeCite this as: BMJ 2019;365:l4423

SMALL IS BEAUTIFUL

We all treat people as well as their diseasesSalisbury says that many GPs choose their specialty to treat people, not just diseases (Helen Salisbury, 15 June). The implication is that other specialists treat diseases rather than people.

When a plastic surgeon meets a baby with a cleft palate for the first time, for example, the family will not realise that this is the start of a longlasting relationship. But the surgeon is aware that the first five minutes are crucial for a successful outcome.

The cancer specialist or cardiologist might not expect to know patients for so long, but if they don’t try to understand the whole patient and their family, they will miss much of the interest of the practice of medicine, never mind the chance to improve diagnosis and treatment.

The relationships between patients, their conditions, and their doctors are always fascinating and constantly evolving—I don’t think there is much difference between the specialist and the GP in this regard. Martin A P Milling, retired consultant plastic surgeon, Chepstow Cite this as: BMJ 2019;366:l4556

HEALTH SERVICE RESEARCH

Privatisation of patient and public involvement

The National Institute for Health Research (NIHR) recently announced a new centre that will merge NIHR INVOLVE and the NIHR Dissemination Centre. The Department of Health and Social Care invited tenders for this new centre before the end of the current NIHR INVOLVE contract with the University of Southampton. The competition was open, with multiple bids received. NIHR said that patients and the public were involved in the procurement process.

The contract is going to a multinational private company, LGC Group. Should

academics, patients, and clinicians be concerned about the apparent privatisation of its research support infrastructure?

How will the centre’s key functions of patient and public involvement and dissemination be integrated? How will patients and public influence research innovation, processes, and production? Are LGC Group bound by the same public interest values, research ethics, equality and diversity policies, and dissemination standards as universities?

We ask for clarification from the Department of Health and Social Care and LGC Group.Sarah Carr, senior fellow in mental health policy, Birmingham; Jonathan Boote, freelance researcher and consultant, SheffieldCite this as: BMJ 2019;366:l4520

NHS CHARGING MIGRANTS

Migrant charging policy is incompatible with good healthcare

Torjesen’s article on charging migrants for careunderstands the implications of the UK’s charging policy for “overseas visitors” that make it fundamentally incompatible with the principles of good healthcare (Feature, 1 June).

The Department of Health and Social Care has refused to publish a review of the effect of charges, even denying access to the health and social care select committee.

Doctors should be familiar with the rules on charging, but asking them to have expert knowledge is unrealistic, nor should they be asked to provide oversight of other staff with completely different responsibilities.

More importantly, this idea distracts from the political motivation underlying the charging regimen, reflecting the government’s determination to use healthcare as a tool of immigration control. Clinicians must continue to press for an end to NHS charging and for full transparency on its effects on individual and public health.Rayah A Feldman, policy and research consultant, Maternity ActionCite this as: BMJ 2019;366:l4518

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David Barrington ShawConsultant physician and cardiologist Royal Devon and Exeter Hospital (b 1929; q Charing Cross Hospital Medical School, London, 1952; MRCS Eng, FRCP Ed, FRCP Lond, MD Lond, FESC), died from cerebrovascular disease on 15 March 2019David Barrington Shaw established specialist cardiology in the peninsula part of southwest England. Appointed to Bristol United Hospitals in 1959, he spent a year as a cardiac research fellow at the University of Colorado before his appointment to Exeter. Within two years he had established cardiology in temporary huts. Intrigued by the number of patients with slow heart rates he started the Devon heart block and bradycardia survey in 1968. He forged links with electrical engineers at Exeter University, and they developed intelligent pacemakers. He served on regional, national, and international committees and contributed to many publications and presentations. Predeceased by his wife, Audrey, he leaves two sons and one grandchild.Brian J Kirby Cite this as: BMJ 2019;365:l4150

Gerald Norman St John PenneyGeneral practitioner Shropshire (b 1927; q Cambridge/Guy’s, 1950; FRCGP), died peacefully from pneumonia on 19 March 2019Gerald Norman St John Penney (“St John”) came to Shropshire with his new wife, Belinda, in 1954. For 41 years he immersed himself in the community around Bishop’s Castle, as a GP and, for 11 years, as mayor. In the newly built surgery he inspired generations of trainees to whom he dispensed wisdom with legendary dry wit, reminding them to “treat the patient as one of your family.” St John was a highly respected clinician, dedicated to traditional values and fighting for the best for his patients. He campaigned to keep the community hospital open, and it was fitting that he spent his last few days there, cared for by staff he knew. Recently widowed, he leaves four sons (one a GP in Bishop’s Castle) and 10 grandchildren.Oliver Penney Cite this as: BMJ 2019;365:l4148

Lorna Tapper-JonesSenior partner Roath House Surgery, Penylan, Cardiff; reader department of public health and primary care, Cardiff University (b 1949; q University of Wales College of Medicine, 1977; BDS, MD, FRCGP), died from disseminated breast cancer on 1 May 2019Lorna Tapper-Jones trained in dentistry before switching to medicine. She was senior partner at Roath House Surgery until she retired in 2011. Lorna joined the College of Medicine in the 1980s and became a reader in the department of general practice. She was responsible for the introduction of the undergraduate Family Case Study and continued her interest in medical education in retirement. Lorna loved her dogs, garden, and music, and also singing in the university choir. In recent years she was terribly ill, but she possessed a unique ability to bring happiness, hope, and good cheer to all those around her. She died peacefully at the Marie Curie Hospice in Penarth.Elizabeth Metcalf, Kamila Hawthorne, Andy Grant Cite this as: BMJ 2019;365:l2419

Derek MathiesonGeneral practitioner Cults Medical Centre, Aberdeen (b 1956; q Aberdeen 1979), died from a rare lung tumour on 31 January 2019Derek Mathieson initially entered practice in Forfar, but he moved back to his native city in 1984. The practice at Cults certainly benefited from this until he retired because of ill health in 2015. He was the clinical tutor there, appointed by Aberdeen University. As a result, many medical students have much to be thankful for by coming in contact with a pragmatic, utterly sensible GP. This was also recognised by his colleagues in the practice and the out of hours cooperative. A substantial number of practising doctors as well as retired doctors sought his medical advice. His wife, Margaret, always provided enormous support to him, especially latterly, with her experience as a senior nurse in the oncology unit in Aberdeen. He leaves Margaret, three children, and three grandchildren. Martin Pucci Cite this as: BMJ 2019;365:l4147

Alistair Cameron MacDonaldGeneral practitioner Norton, Cleveland (b 1926; q Aberdeen 1948; FRCGP), died from heart failure due to amyloid cardiomyopathy on 2 June 2018Alistair Cameron MacDonald (“Sandy”) was recruited as a missionary by the Church of Scotland during his houseman’s year. After one term of the course in tropical medicine at Liverpool, he left for Nigeria in 1949. He later completed the course and became a fellow of the Royal Society of Tropical Medicine and Hygiene in 1957. In 1952 he became medical superintendent of Presbyterian Rural Health Services in Nigeria; he left Nigeria in 1961. Back in Scotland he trained in general practice and in 1963 started at Norton Medical Centre, in Teesside, England. He was a representative on the local medical committee of the BMA and became involved in GP training. Predeceased by his wife, Freda, in 2012, he leaves two sons; four grandchildren; and one great granddaughter.Paul MacDonald Cite this as: BMJ 2019;365:l4171

Cathleen ElliottGeneral practitioner (b 1921; q Birmingham 1950; MBE), died after a fall resulting in a fractured skull on 19 April 2019Cathleen Elliott (“Cath”) worked as a nurse during the second world war before she became a doctor. After house jobs at Birmingham General Hospital, she went to New York and became resident medical officer at the Babies Hospital. (She would have earned twice as much for half the hours if she had gone as a nurse.) In 1952 she returned to Birmingham to work at Birmingham Maternity Hospital and then the Birmingham Children’s Hospital. In 1953 she joined a general practice in Bromsgrove, where she worked until she retired in 1981. She was an inaugural member of the Bromsgrove Bereavement Counselling Group and an active member of Save the Children Fund, for which she was presented with an MBE by the Queen in 2007.R C S Spires Cite this as: BMJ 2019;365:l2418

Longer versions are on bmj.com. Submit obituaries with a contact telephone number to [email protected]


When 92 year old Nobel laureate Sydney Brenner died in Singapore in April, media outlets worldwide ran the news. The South African scientist and physician inspired many headlines during his seven decade career. After all, Brenner helped decipher the genetic code.

Brenner’s research, his early and active role in the Human Genome Project, and his mentoring of so many younger scientists changed science and medicine globally.

Early life and careerBrenner was born in Germiston, a small town near Johannesburg. He grew up in rooms behind the shoe repair shop owned by his parents who were Latvian and

Lithuanian Jewish immigrants.One of his father’s customers,

a Miss Walkinshaw, saw the three year old Sydney reading and persuaded Morris to accept a free kindergarten place for his son. Brenner raced through his school years and completed high school in December 1941, at the age of 14. He won a town council bursary to study at the University of the Witwatersrand and started medical school at 15. He travelled the 13 km to the university by bike, train, and on foot. When he completed medical school, he was still too young to practise, so he started a bachelor of science in anatomy and physiology. By 1947 he had completed a master of science as well, researching cell genetics.

“I was not a good medical student and had an erratic career—brilliant in some subjects, absolutely dismal in others,” Brenner later said. “In

my final year I failed medicine, scraped through surgery, but got a first class in the third subject, obstetrics and gynaecology. I had to go back and repeat medicine and surgery, and six months later, in July 1951, I finally received the degrees of MB BCh.”

In 1952 Brenner won a scholarship to undertake a doctorate in chemistry with Cyril Hinshelwood (another future Nobel laureate) at Exeter College, University of Oxford. In London, in December 1952, Sydney married a fellow South African, May (Covitz) Balkind, and became a stepfather to her 5 year old son, Jonathan. They returned with their new son Stefan to South Africa in 1954.

Genome studies and Nobel prizeIn 1953 hearing of Cambridge’s success in determining the structure of DNA, an excited Brenner had driven to the Cavendish Laboratory (now the Medical Research Council Laboratory of Molecular Biology) in Cambridge to see the model. It proved to be a watershed moment in his career and life. In 1956 the Brenner family moved to Cambridge. Brenner shared an office with Francis Crick, collaborated with him, and began his long, successful career with the MRC. In 1957 he helped show that the DNA code instructs the building of proteins in our cells. In the early 1960s, he co-discovered (with François Jacob and Matthew Meselson) the existence of messenger ribonucleic acid (mRNA) and showed that the nucleotide sequence of mRNA determines the amino acid order in proteins.

In 1979 Brenner became the director of the MRC laboratory. In 1986 he established the MRC Unit of Molecular Genetics. In 1995 he founded the Molecular Sciences Institute in Berkeley, California. He was also the founding president of the Okinawa Institute of Science and Technology in Japan. He began his work in comparative

genomics, studying the Japanese puffer fish. In 2000 he joined the faculty of the Salk Institute for Biological Studies in San Diego.

In 2002, Brenner, along with two of his former postdoctoral fellows, H Robert Horvitz of the Massachusetts Institute of Technology and John Sulston of the Wellcome Trust Sanger Institute in the UK, were awarded the Nobel prize in physiology or medicine. They received the award for their creative research on a worm, Caenorhabditis elegans. Brenner had seen a potential role for C elegans in investigating developmental biology, genetics, and neurobiology. They established and used the tiny transparent worm as an experimental model system. They also identified key genes regulating organ development and programmed cell death, and showed that corresponding genes exist in higher species, including humans. C elegans became the first multicellular organism to have its complete genome sequenced.

In 2003 Brenner became Singapore’s first honorary citizen, for being the driving force behind the creation of the country’s Institute of Molecular and Cell Biology and the Agency for Science, Technology, and Research Graduate Academy.

At the time of his death, Brenner was a distinguished professor emeritus at the Salk Institute. He received countless awards, fellowships, and honorary degrees over the course of his career.

At 89 he had life saving heart valve surgery. At 90, with lung disease and using an oxygen tank to help him breathe, he was living in a hotel in Singapore and continued to work daily. He was predeceased by his wife, May, in 2010 and by his stepson in 2018. He leaves three children.Barbara Kermode-Scott, Comox, Canada [email protected] this as: BMJ 2019;365:l1976

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They identified key genes regulating organ development and programmed cell death

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Sydney BrennerNobel laureate and molecular biologist who specialised in comparative genomics

Sydney Brenner (b 1927; q University of the Witwatersrand, Johannesburg, South Africa, 1951; MSc, DPhil Oxf, FMedSci, FRCP), died 5 April 2019

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