(The Lancet) – The great Aneurin Bevan founded the UK National Health Service (NHS) not as a charity, but as an institution that belonged to everyone, so that sudden poverty was not added to the pain of illness. Nowadays, there is (rightly) an expectation that the NHS should provide more than just relief from poverty caused by sudden illness, but also, increasingly, that it should provide everything we can imagine that we need to maintain good health, whether our livelihoods are in jeopardy or not. Is this expectation realistic in the 21st century, with an ever more aged population with complex multimorbidities? One driver (although not the only one) of spiralling costs and expectations is the price of novel biological therapies. In this regard, the current situation is wholly unsatisfactory, particularly in relation to the current mode of price-setting by pharmaceutical companies.
It is sad that no politician has dared to address the politically unpalatable issue that, whichever political party is in power, and whatever fiscal system is in place, rationing of health care is inevitable. The idea that everyone under every circumstance can have all possible therapeutic interventions is, and always has been, a myth. Furthermore, no party has seriously addressed the issue of how we should ensure equity given this inevitable need for rationing, or had a grown-up discussion with the public.
Perhaps the best example of how decisions on rationing health care should be made was the 1997 case of Soobramoney versus the province of KwaZulu-Natal, South Africa. Mr Soobramoney was impoverished and had end- stage renal failure, but was denied dialysis by KwaZuluNatal on the grounds that, because resources were limited, KwaZuluNatal policy was to offer dialysis only to people eligible for a kidney transplant. Mr Soobramoney indisputably had severe cardiovascular comorbidity that rendered him ineligible to be wait-listed for a transplant. The case was urgently appealed to the South African Constitutional Court, the highest tribunal in the land. The judgment1 by Arthur Chaskalson, then President of the Constitutional Court, was a model of logic and scholarship. He said that “the hard and unpalatable fact is that if [Mr Soobramoney] were a wealthy man he would be able to procure such treatment from private sources; he is not and has to look to the state to provide him with the treatment. But the state’s resources are limited and the appellant does not meet the criteria for admission to the renal dialysis program.” Judge Chaskalson held that resources were limited, and it was not for the courts to intervene, provided that decisions were based on rational policies. KwaZulu-Natal won the case and, sadly, Mr Soobramoney died within a few days. Constitutional Court Justice Edwin Cameron, writing years later, could not see how the Constitutional Court could have found otherwise,2 and neither can I. Thus, it follows that we need a body like the UK National Institute for Health and Care Excellence (NICE)—which might be a surprising statement from me, given my past criticisms of that body3 —that, among other functions, determines whether expensive medications represent value for money. We need to acknowledge that NICE is nice, and must be about rationing, and we must not cavil when they act to ration.
The question remains how we apply objective principles to the issue of expensive medications. Currently, the pharmaceutical industry holds all of the power. They set the price, with no transparency as to the business model used to decide this, and NICE are pilloried for not allowing the high-cost, highly hyped medication to be prescribed to patients who are desperate to find a way out of a deep dark hole. NICE and the NHS bear the burden of the decisions made by the pharmaceutical industry, and this cannot continue.
Clearly, those who develop new medications deserve proper intellectual and financial rewards, as do those who have invested capital to support early-stage drug development. However, there is a great gulf between the investigators at the bench and the pharmaceutical companies at the cash register. A recent example acutely highlights the problem. Women with chronic cough unrelated to asthma or any other airway disease have a disabling and distressing condition for which, until the past few years, there was no treatment. Early phase 2 studies of the P2X3 receptor antagonist AF-219 showed extremely promising results,4 which need confirmation in a large phase 3 study. On the basis of preliminary results, Merck Sharp & Dohme bought the compound for a reputed US$1·25 billion.5 This move can only be because the company think that they can pass this vast sum on to whomsoever will foot the bill for treatment worldwide, be it patients, insurance companies, or the NHS— as well as making profits on top. This huge payment presumably means that the eventual price of the medication will be grossly inflated, and be passed on to the consumer. In writing this, I am not attributing blame to anyone, but merely highlighting the current situation.
I suggest that it is too late to start negotiating the price after the phase 3 trials have been done. It is surely unethical to do clinical trials using people from populations that will be unable to benefit from the treatment if it becomes licensed—a view enshrined in the Helsinki declaration. In the future, a condition of permitting phase 3 trials to be carried out must be an agreement, made in advance, about how the price of the medication will be fixed (eg, in terms of quality-adjusted life-years). We have sold ourselves short—brilliantly conceived phase 3 studies, most perfectly executed by the best investigators on the planet, without which medications could not get licensed, have been performed with pharmaceutical companies being invoiced for sums which are a fraction of the subsequent profits they make. Thus, it is my contention that, as part of the routine ethical and other reviews of potential trials, the question “cui bono?” must be asked and answered; unless the way pricing is subsequently determined is agreed in advance, is transparent, and takes account of real benefits to patients, large phase 3 trials are no longer ethical and should not be done.
Section of Paediatrics, National Heart and Lung
Institute, Faculty of Medicine, Imperial College
London, London, UK; Department of Paediatric
Respiratory Medicine, Royal Brompton Hospital,
London SW3 6NP, UK