Programs for expedited review may be preferentially reducing the development costs for conditions with lesser disease burden, potentially making investments in addressing the most significant disease burdens even less appealing and exacerbating the market failure further.

The World Health Organization (WHO) estimates that 1.7 billion people around the world are in need of measures to prevent or treat neglected tropical diseases (NTDs), conditions that collectively account for as many as 200,000 deaths/year and a burden of disease running in the hundreds of billions of dollars per year. This vast unmet medical need reflects the global pharmaceutical industry’s focus on developing products for US markets, where efficient channels for product sales and few limits on drug pricing provide companies with the opportunity for robust returns on investment and profit. US markets, however, account for less than 4% of the global burden of disease. The greatest disease burden is associated with conditions prevalent in low- and middle-income countries, where the available market is typically inadequate to justify the investment cost; a classic instance of market failure.

From 1975-1997, less than 1% of new drug approvals in the USA and EU were indicated for tropical communicable diseases. A decade later, from 2000-2011, only 1% of new drug approvals (New Chemical Entities) were indicated for NTDs, and only 1% of all clinical trials involved products that might address this unmet medical need. A new report in the British Medical Journal Open (BMJ Open) from the Center for Integration Science and Industry at Bentley University demonstrates that this trend continued through the decade before COVID (2010-2019) with only 1.8% of the new drugs indicated for tropical diseases. The BMJ Open study further demonstrates that, while half of the new product approvals were for conditions in the top quartile of US disease burden, there was no association between the number of product approvals and conditions contributing the most to the global disease burden.

Classical economic theory posits a central role for the government in rectifying such market failures through regulation, subsidies, or public investments. These interventions are variously designed to adjust either the cost basis for bringing products to market or the structure of the market such that the potential returns to industry are sufficient to warrant private investment. These principles underlie a number of policies in the US (and analogous policies in the EU) intended to incentivize industry development of drugs with characteristics that have made industry investment unattractive. These include the Orphan Drug Act for rare diseases and programs that provide expedited review of products for selected “serious diseases” with attributes that make development relatively unfavorable, including special “fast track”, “breakthrough”, “accelerated”, and “priority” review programs. These programs reduce the requirements, timelines, or costs of development, provide tax breaks, or create indirect subsidies (vouchers) to reduce the net cost of development or provide extended patent protection to increase the market potential.

The orphan drug and expedited review programs have dramatically changed the landscape of pharmaceutical development. They have helped create more than 500 products for “orphan” diseases since 2000 with almost 60% of all approvals between 2010-2019 taking advantage of at least one designation for “expedited” review. While these policies were primarily designed to address unmet needs in US markets, the FDA has issued guidance on the application of these policies to incentivize product development for NTDs, and one program, the “Tropical Disease Priority Review Voucher Program,” focuses directly on such diseases.

But the critical analysis in BMJ Open not only shows that, despite such guidance, only meager progress has been made in developing products for diseases with the greatest disease burden, and that programs for expedited review may actually be making things worse. Supported by funding from INET, the study examined 387 drugs approved between 2010-2019 and found that 207 of them were granted a "priority review" designation. Only seven of these, however, specifically target tropical diseases. No less worryingly, the research found a negative association between drugs being designated for expedited review and the burden of disease associated with the conditions they were approved to treat. Thus, programs for expedited review may be preferentially reducing the development costs for conditions with lesser disease burden, potentially making investments in addressing the most significant disease burdens even less appealing and exacerbating the market failure further.

What initiative might rectify this situation? A variety of non-profit entities and public-private partnerships (PPPs) have emerged to tackle this unmet need. These include a number of product development partnerships (PDPs) focused explicitly on developing drugs, vaccines, or diagnostics for conditions prevalent in low- and middle-income countries. Examples of such partnerships are the Global Alliance for TB (TB Alliance), Medicines for Malaria Venture (MMV), and Drugs for Neglected Diseases Initiative (DNDI). These entities raise capital primarily through government funding and philanthropic contributions and typically rely on partnerships or contracts with the private sector for product development.

A survey of funding for research on products for neglected diseases conducted by Policy Cures Research has identified more than $60 billion in total funding for product development related to “neglected diseases” (not including Coronavirus) from 2007-2022. Contrary to the popular perception that these initiatives have been driven by private philanthropy, the data show that 66% of the funding came from public institutions (government): 20% from philanthropic sources: and 13% from industry.

The money supported $13.7 billion for basic research on neglected diseases; $13.6 billion on new drugs; and $21.5 billion on vaccines over these 16 years. Nevertheless, the BMJ Open study could identify only two new drug approvals in the period from 2010 to 2019 for tropical diseases that were sponsored by PDPs. One was Pretomanid approved in 2019, developed by TB Alliance; the other was Moxidectin approved in 2018, developed by the Medicines Development for Global Health. (Note that the BMJ Open study did not include vaccines.)

This leads to a crucial question: Can the non-profit sector provide the firepower necessary to address the global burden of disease?

In a comprehensive study of the global non-profit sector, the late Lester Salamon and his collaborators defined the “broad non-profit sector” as comprising “entities that are formal organizations having an institutionalized character; constitutionally independent of the state and self-governing; non-profit-distributing; and involving some degree of volunteerism” and documented their growing financial resources, employment, and impacts. This research ascribes growth of the non-profit sector over recent decades to the widespread adoption of the “neoliberal consensus” that many social services might be provided more efficiently and effectively through partnerships with the private sector (including both for-profit and non-profit entities) than by government or markets alone. Significantly, this research also showed that, contrary to popular perception, the non-profit sector was not supported primarily through philanthropy, which provided only 11% of financial support for global non-profit enterprise (data from 22 countries, for 1995), but that proceeds from commercial activities provided 49% of the financial support and government provided 40%.

The panoply of non-profit entities committed to addressing the global burden of neglected diseases through advocacy, education and research, health, or social services related to neglected diseases are well within the mainstream of traditional non-profit activities identified by Salamon and his collaborators. One could also argue that PDPs focused on discovery, development, or commercialization of novel pharmaceutical products are not conceptually different than other non-profits involved in commercializing goods or services in the healthcare or educational sectors. The question, however, is whether non-profit business models can really rectify the market failures that have led to a paucity of products for neglected diseases.

In our view, the crucial feature of non-profit entities is not the absence of profit, but rather the fact that they are characteristically prohibited from distributing cash resources to shareholders. Since 2010, public (for-profit) biopharmaceutical companies have distributed almost $1.6 trillion in cash to shareholders through dividends or stock buybacks, representing approximately 16% of their total revenues, an amount slightly larger than their total profit (net income). Thus, while the absence of cash distributions to shareholders could contribute to lowering drug prices or realizing a return on investment, the size of the effect is unclear. Even putting all that money back into research might not lead to a quantum leap in the production of the drugs most urgently needed by the world’s poor.

Non-profits are more likely than for-profit firms to attract philanthropy to support product development or treatments. The available data suggests, however, that philanthropic contributions comprise a minor fraction of the capital resources required to address neglected diseases. Nor is there evidence that non-profit entities benefit substantially from discounted or donated goods or services, or that non-profit firms can systematically develop new products more efficiently or at a lower cost than for-profit firms.

Non-profits might also face some peculiar problems of their own. Since most PDP activities are likely to be tax-exempt, non-profit initiatives may not benefit from government incentive programs that reduce corporate tax burdens or provide tax credits, unless such benefits can be sold. Thus, it is not evident that the financial model of non-profit enterprise would really address the market failures confronting neglected disease. The fact that two out of seven drugs for tropical disease described in the recent BMJ Open paper were developed by non-profits (TB Alliance, MDGH) suggests that more research is required to understand these business models and the role they can play in addressing the global burden of human disease.

‘Unhinged’ letter to all staff, organisers and officers includes ‘disgusting’ section about Palestine

Unite general secretary Sharon Graham has sent a letter to all the union’s staff, organisers and officers that has been described as an ‘unhinged’ attempt to counter criticisms. Skwawkbox will publish analysis of the various sections separately – and will first cover what Unite figures have described as Graham’s ‘disgusting’ comments on Israel’s slaughter of Palestinian civilians in Gaza.

The letter claims that Graham and Unite have led on opposition to the mass murder in Gaza – despite Graham being widely criticised for her silence on the issue and insiders saying that she had to be pressured into a proper statement on Gaza at all.

And the section, which is titled ‘Palestine’, goes on to make clear that while Unite has given a one-off donation (one that Skwawkbox understands was given suddenly and without approval by Unite’s elected executive) to Doctors without Borders, Ms Graham and the union under her will always prioritise defence industry jobs above any outside issues, despite the union’s official, democratic position in support of sanctions and a boycott against Israel.

The full section reads:

Palestine

Of all the issues that have been used in these attacks, probably the most abhorrent is the attempted weaponisation of the conflict and the deaths of thousands of innocent civilians and the collective punishment of the people of Gaza.

Unite, through the General Secretary and the Chair of the Union and the Executive Council, was the first major union to publicly and unambiguously call for a permanent ceasefire in Gaza. We were very clear. We have watched on with horror the bombardment and destruction of Gaza, and the unbearable terror, suffering and death of its innocent civilians. We have been unequivocal that the deliberate killing of civilians, hostage-taking and collective punishment are war crimes and should be identified as such.

Unite has also donated £50,000 to Médecins Sans Frontières/ Doctors Without Borders specifically to help the many victims of this horrific conflict. Most recently the General Secretary has written to the Palestinian General Federation of Trade Unions (PGFTU) offering our solidarity after the horrific bombing of their Gaza headquarters which, alongside providing services to workers, was also functioning as a kindergarten and bakery.

However, we cannot and will not endorse any organisation which decides unilaterally and without any discussion (let alone agreement) with the workers themselves, to support the targeting of our members’ workplaces or their jobs. To be clear, this will not happen. No outside body, no matter what their political position, will be allowed to dictate terms to our Union and our members.

It is important to highlight here that it is a core principle of Unite that as a trade union the ‘first claim’ on our priorities is always the protection and advancement of our members’ interests at work. It is very simple. Unite cannot and never will advocate or support any course of action which is counter to that principle. We are a trade union, not a political party or single-issue campaign group.

Therefore, there is no contradiction for a trade union to hold a position of solidarity with Palestinian workers, while at the same time refusing to support campaigns that target our members’ workplaces without their support. Similarly, we cannot be expected to affiliate to organisations that actively work against our members and their jobs.

Examples include groups that look to build networks inside trade unions to undermine the defence industry or demand the disbandment of NATO and AUKUS. Whatever anyone may think personally about those objectives is irrelevant. We are a trade union with thousands of members employed in the defence industry. It is the views of affected members that take precedence in a trade union. That will not change and nor should it. Unite members have recently been attacked directly, been spat at and called “child killers”. We cannot and will not endorse this.

Emphases added

One furious senior insider told Skwawkbox:

She’s effectively saying members working in defence don’t care if what they make ends up killing women and children in Gaza – only jobs matter. Has she bothered asking any of them?

Another said:

Unite’s official position, democratically reached repeatedly at conference and confirmed again just last summer, is that it supports Boycott, Divestment and Sanctions against Israel. We didn’t add ‘except where it might affect defence jobs’. We’ve also voted for the end of trade agreements with Israel. This is disgusting by Sharon.

Sharon Graham has been alleged by insiders to have:

• banned Unite officials and national banners from pro-Gaza protests
• banned and smeared films and books exposing the ‘Labour antisemitism’ scam
• placed an official under investigation who refused to cancel a Palestine solidarity fringe event at Labour’s 2023 annual conference
• told her chief of staff to threaten a soon-to-retire official with the loss of a pension bonus if he did not soften his support for Palestinians

Her supporters also prevented debate and votes on Gaza at a meeting of the union’s elected executive earlier this month.

According to human rights group Euro Med Monitor, since 7 October last year Israel has killed over 40,000 Palestinians in Gaza and wounded more than double that number, overwhelmingly women and children and many of them with life-changing injuries, while Gaza’s health and school systems have been bombed into collapse, often using US- and UK-made weapons and systems. More than a million people have been forcibly displaced and Gaza is in famine because of Israel’s blockade of food and vital supplies. Israel is formally on trial for genocide before the International Court of Justice and ordered to stop its slaughter – and has been found by UN human rights investigators to be committing genocide.

Unite was contacted for comment but did not respond by the press deadline.

SKWAWKBOX needs your help. The site is provided free of charge but depends on the support of its readers to be viable. If you’d like to help it keep revealing the news as it is and not what the Establishment wants you to hear – and can afford to without hardship – please click here to arrange a one-off or modest monthly donation via PayPal or here to set up a monthly donation via GoCardless (SKWAWKBOX will contact you to confirm the GoCardless amount). Thanks for your solidarity so SKWAWKBOX can keep doing its job.

If you wish to republish this post for non-commercial use, you are welcome to do so – see here for more.

Outside the European Union, the UK is becoming a dumping ground for toxic substances.

By George Monbiot, published in the Guardian 18th March 2024

It’s a benefit of Brexit – but only if you’re a manufacturer or distributor of toxic chemicals. For the rest of us, it’s another load we have to carry on behalf of the shysters and corner-cutters who lobbied for the UK to leave the EU.

The government insisted on a separate regulatory system for chemicals. At first sight, it’s senseless: chemical regulation is extremely complicated and expensive. Why replicate an EU system that costs many millions of euros and employs a small army of scientists and administrators? Why not simply adopt as UK standards the decisions it makes? After all, common regulatory standards make trading with the rest of Europe easier. Well, now we know. A separate system allows the UK to become a dumping ground for the chemicals that Europe rules unsafe.

While negotiating our exit from the EU, the government repeatedly promised that environmental protections would not be eroded. In 2018, for example, the then environment secretary Michael Gove, in a speech titled Green Brexit, claimed “not only will there be no abandonment of the environmental principles that we’ve adopted in our time in the EU, but indeed we aim to strengthen environmental protection measures”. Such pledges turn out to be as dodgy as a £3 coin, with Boris Johnson’s head on it.

Our proudly sovereign regulatory system immediately descended into total chaos: chaos of the kind that the warlord capitalists who backed the leave campaign might have been hoping for. It took the UK’s Health and Safety Executive (HSE) until last month to publish its chemicals regulation work programme for the financial year 2023-2024. That was, erm, six weeks before the period expired. You’ll remember, of course, how Brexit would enable us to escape the “inefficiencies” of Brussels bureaucracy.

As the campaign group Chem Trust documents, our shadow version of the EU system, called UK Reach, is beset by underfunding, understaffing, a skills crisis and an impossible workload. It looks to me like the kind of failure-by-design that afflicts so much of environmental regulation in the UK.

This dysfunction leaves us exposed to toxins now being banned or restricted in Europe. For example, tetraethyl lead has long been banned from fuel for surface vehicles. But it continues to be used in aircraft fuel, ensuring we are sprayed with a chemical that causes neurological disorders. The EU, after long resisting the obvious step, has at last ruled that it must be phased out. But the UK hasn’t. It will remain legal here. The same goes for endocrine-disrupting chemicals in children’s toys, formaldehyde, brominated flame retardants and the microplastics intentionally added to fertilisers and artificial sport surfaces.

The EU is far from perfect. It has backtracked on some of its own commitments. But at least it’s doing something about chemicals that cause cancers and other illnesses and devastate ecosystems. Since we left the bloc, UK regulators have yet to adopt a single new ban or restriction of a harmful substance. Brings a lump to the throat, this patriotic self-reliance, doesn’t it? Or perhaps to the breast, or stomach, or liver.

In some respects, we’ve even been spiralling backwards. The government has decided that workplace exposure limits on dimethylformamide, and restrictions of polycyclic aromatic hydrocarbons in synthetic sports pitches, of lead in PVC products and of hazardous substances in disposable nappies are “not a priority for action this year”. Part of its reasoning is that it has yet to see evidence that these substances pose a risk that is “specific to Great Britain”. Does their use in the UK present different risks to their identical use elsewhere? Perhaps the bulldog spirit of this sceptred isle protects us from chemicals that afflict the lesser beings overseas.

In the EU, there is now a total ban on the use of neonicotinoid pesticides – perhaps better labelled ecocides, thanks to their remarkably wide range of impacts. But every year since we left the EU, the UK government has granted an “emergency” exemption from the supposed ban here, following lobbying by sugar beet producers and the National Farmers Union. In August 2020, British Sugar asked for “no more than three years… to give us time to develop alternatives”. Given that it granted yet another authorisation in 2024, perhaps the government could ask British Sugar’s managing director how his company is getting along. He shouldn’t be hard to find. He’s married to the health secretary.

The more we learn, the more we realise how dangerous chemicals approved without proper testing or consideration can be. New findings, for instance, on the health effects of PFAS compounds – “forever chemicals” – and on the ecological and health impacts of pesticides, and on the effects of microplastics in soil show why we should apply the precautionary principle. By the time we discover that a substance is more hazardous than first believed, it is embedded in our ecosystems, our bodies and our lives.

While the UK government appears incapable of developing new public protections, it is also mysteriously unable, following lobbying, donations and taps on the shoulder, to uphold and enforce the regulations we do possess. Every body that’s supposed to protect us from environmental harm – such as the Environment Agency or the HSE – is woefully underfunded, underpowered and demoralised. This is where most deregulation happens: not in the formation or de-formation of rules, which, at least in theory, is subject to parliamentary debate, but in the government’s unwillingness to apply them, which is not.

This is why a group of us, called Fighting Dirty, are taking the government to court over its multiple failures to protect people and ecosystems from hazardous chemicals, beginning with its outrageous refusal to test or regulate the many toxins being spread on farmland in sewage sludge. We have just been granted permission for a high court hearing. Such legal actions, difficult and expensive as they are, are a last resort, when regulatory standards and the agencies supposed to uphold them have all but collapsed.

Brexit was sold to us on the grounds of intangible gains: a sense of autonomy and pride, particularity and independence. These intangible gains are accompanied by tangible losses: real impacts on our health and wellbeing. We might have left the EU, but we did not escape the demands of predatory capital. Far from it: freed from European restraints, they trickle insidiously into our lives.

www.monbiot.com

Despite mental health being arguably the most significant health crisis facing the UK, Jeremy Hunt didn't mention it once during his Spring Budget.

One in four people in the UK are affected by mental health, with mental illness costing the country an estimated £118 billion annually – equivalent to 5% of GDP.

According to NHS data, the number of people in contact with mental health services has increased by almost 500,000 since 2020.

For these reasons, mental health charities did not welcome the Budget.

Mind was particularly critical of the decision not to commit more funding to the roll-out of 'Right Care, Right Person’, an initiative that aims to ensure that the right agency deals with health-related calls, rather than police forces being the default first responders.

"It is simply impossible to take a million hours of support out of the system without replacing it with investment," the charity said. "Failing to properly fund NHS mental health crisis services while instructing police forces to step back from mental health calls is an unsafe and frankly irresponsible decision."

Given that the NHS is facing extreme challenges in almost every aspect of its running, it does not have the capacity to handle the increasing number of people in the UK reaching crisis point with their mental health.

The Budget promised to deliver an NHS productivity plan, by making its technology more efficient and reducing healthcare time on admin. While this may ease time pressure for healthcare workers, it is not focused enough to address the broader, more systemic issue of underfunding and under-resourcing.

A recent British Medical Association report highlights an additional problem: mental health professionals are becoming so disillusioned that they are unable to work themselves. In September 2023, one in seven medical posts in NHS mental health trusts were vacant.

According to a report shared with The Independent on March 25, emergency departments are so overwhelmed, A&E staff are unable to look after the most vulnerable mental health patients or treat them with compassion. According to medical records, more than 40% of patients who needed emergency care due to self-harm or suicide attempts received no compassionate care, the newspaper reported.

It appears as if the Conservatives view our mental health crisis as a primarily financial burden, reprimanding the growing population of people out of work, many for mental ill-health.

The Autumn 2023 Budget, for example, announced the Government’s plan for short-term changes to how the Department for Work and Pensions classifies who is fit to work. It proposed stricter sanctions for people previously deemed unable to work, potentially pushing those who are too mentally unwell back into work to avoid losing access to support.

The driving force for these changes seems to be primarily one of labour, productivity, and money rather than addressing the underlying socio-economic factors such as, but not exclusively, racism, homelessness, poverty, and sexism.

People under 25 seem to bear the brunt of these pressures.

A week before Hunt's Budget, Young Minds delivered an open letter to the Chancellor, signed by 15,000 campaigners, urging the Government to invest in early intervention hubs for young people struggling with mental health.

Meanwhile, a new report published by the Children’s Commissioner showed that more than a quarter of a million children and young people are awaiting mental health support, and referrals for under-18s are up by 53%.

According to the Mental Health Foundation, 50% of mental health conditions emerge by the age of 15 and 75% by 24, so early intervention could help prevent severe mental health issues which may impact work and life quality into adulthood.

Responding the the Budget, Laura Bunt, chief executive at YoungMinds said, “Ultimately, until we focus on the systemic drivers of poor mental health, we will be fighting a broken system. We need a plan that works across Government, one that prioritises early intervention and prevention; we need this Government to wake up and take steps to stop this crisis from getting worse.”

The Government has also repeatedly fallen short on promises to deliver on mental health reform.

A previous commitment to a 10-year mental health plan to "level-up mental health across the country and put mental and physical health on an equal footing" was scrapped and absorbed into a ‘Major Conditions Strategy’. That aimed to tackle wider ill-health and removed the focus on mental health.

Recently announced National Insurance cuts will also do little to help those with low incomes, providing almost no support for those on the lowest threshold. Financial insecurity is a crucial indicator of poor mental health. Children from the poorest 20% of households in England are almost four times more likely to have serious mental health difficulties by age 11 than those from the wealthiest 20%.

Fazilet Hadi, head of policy at Disability Rights UK, told Byline Times that the Budget “totally ignored the deepening poverty and lack of support being experienced by millions of disabled people, including those experiencing mental distress".

"There are to be no further cost of living payments and the Household Support Fund, which enables councils to give discretionary payments, is only extended by six months,” she added.

The burgeoning mental health crisis is evident, with a high cost to the long-term productivity and growth the Conservative Party desires. Unless the Government prioritises mental health service funding and effective measures supporting the young and most vulnerable are in place, the crisis will only get worse.