CANCER AND ADJUSTING PROBLEMS
An immediate problem with adjusting for quality of life is clearly apparent – how do we define how much a person’s quality of life is affected? For example, Mr A leads a sedentary life and mainly enjoys watching TV for recreation, therefore an impairment which stops him running will matter very little. Mr B, however, is a keen triathlete and finds the same loss of mobility hugely distressing. Clearly, any quality adjustment is subjective and will depend on those affected. Somehow an average value must be arrived at and added to the equation.
A second problem is how to measure the gain in survival. This may seem straightforward, but often licensing trials will focus on the time taken for the disease to worsen (so-called ‘time to progression’) rather than overall survival. Subsequent ‘salvage’ treatment may, therefore, improve the outcomes of the patients in the initial control arm of the trial. Endpoints for these trials are set by the regulatory authorities, such as the US Food and Drug Administration and the European Medicines Agency, and determine whether a company is granted a licence to market their product. However, just because a drug can be marketed does not mean that a healthcare system will buy it.
In order to illustrate how this process works, I will run through the recent trials carried out with a new drug in advanced kidney cancer. In the trial, patients on the placebo were deteriorating twice as quickly as those on the new drug called sorafenib. The Independent Data Monitoring Committee for the trial decided the study should be stopped on ethical grounds and all the placebo patients still alive were offered the new drug. When the overall survival times were subsequently analysed, the patients initially on the new drug lived longer than those on placebo. However, due to the salvage effect from the crossover from placebo to active drug, the survival advantage for the new drug was much smaller than would have been expected from the effect on time to progression. It is thus impossible to calculate the survival benefit of sorafenib in advanced kidney cancer as this trial can never be ethically repeated with a no-treatment arm. Any estimates for the cost per QALY for this disease are thus doubly flawed – the effect on quality of life is subjective and the true survival gain unknown. This double uncertainty paralysed the UK decision-making process for kidney cancer from 2006 to 2009.
The use of decision-making based on quality-adjusted survival has been pioneered extensively by a UK body with the somewhat Orwellian title of National Institute for Health and Clinical Excellence, usually known as NICE. This body seeks to advise the health service which treatments it should purchase on behalf of the patients and which treatments are not considered good value for money and should not be routinely funded. NICE does not consider unlicensed or experimental treatments. Some other European countries have adopted similar methodologies, but as yet the more free-market approach in the USA has shied away from such central direction. NICE will often take months or even years from the initial licence to give an opinion on a drug. In the UK, the NHS funding is split between ‘purchasers’ and ‘providers’. Currently, the purchasers are called Primary Care Trusts (PCTs) and are tasked with making the same decisions (to buy or not to buy a particular treatment) on a local basis. At the time of writing, in 2011, this purchaser role is set to be transferred to family doctors (GPs) under forthcoming NHS reforms. The current PCTs discharge this role with varying degrees of competence and thoroughness, often simply providing the cheapest option until forced to provide a more expensive one by subsequent NICE guidance. This leads in turn to the (in) famous UK post-code lottery – as PCTs are geographically based, access to any NHS treatment is determined by the patient’s address and the local PCT decision-making process. In 2008, this resulted in the highest spending PCTs allocating around £15,000 per patient for cancer care compared to around £5,000 for the lowest spending ones. In my own clinic, patients with a Birmingham post-code (a high-speed area) enjoy good access to, for example, the latest kidney cancer drugs. Conversely, most of the surrounding counties have relatively low cancer drug spends and access to the same drugs is severely restricted. As patients clearly talk to each other, in the waiting room, the level of frustration and anger generated can be readily imagined. We carried out an audit of survival times by post-code for our patients with advanced kidney cancer. Patients from the low-spend areas survived around 7–8 months on average, compared to around 2 years for those from the higher spending Birmingham area – a very real and worthwhile difference. In addition, patients denied access to the expensive drugs had roughly three times as many visits to hospital due to increased rates of disease complications from their untreated cancer. This state of affairs persisted for 3 years from 2006 (when the new kidney cancer drugs were first licensed) to early 2009 when NICE finally recommended that one of these drugs, sunitinib, be made available to all kidney cancer patients (though access to other recently licensed kidney cancer drugs remains heavily restricted). Clearly, the PCTs not funding these drugs would argue that they have used this money elsewhere to produce a bigger gain for a different group of patients. I am not aware, however, that there is any good evidence that poorer outcomes occur in other groups of Birmingham patients compared to their shire county neighbours as a result of lack of funds. The present UK system strikes me therefore as cumbersome, unnecessarily bureaucratic, and in many cases ill-informed. Those making the decisions, allegedly on behalf of the public, are not in any way publicly accountable for their decisions – they are not elected, for example – and often will not publicly defend them. On the other hand, in an era of rising costs, an ageing population, and shrinking budgets some form of choice must be made and thus structures like NICE will probably become more common worldwide in the future.