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Home » Breast Cancer, Health, Healthcare Policy

Will access to innovative cancer drugs bankrupt European healthcare?

Submitted by on 14 Jul 2017 – 10:40

Dr Martine J Piccart  and Dr Noam Ponde from Institut Jules Bordet make an extensive study of the European drug scenario and note that a major reform in drug development is necessary, with “risk sharing” by governments If Europe is to fight cancer efficiently while retaining its current health care systems

Public healthcare is a core characteristic of European society, guaranteeing universal access to affordable healthcare to the citizens of European Union (EU) member states. EU citizens live longer and consequently cancer becomes an increasing public health concern.(1)

Decades of research to understand the molecular and genetic underpinnings of cancer have led to new kinds of treatment, namely molecularly-targeted therapy and immunotherapy. These innovative drugs attack specific molecules that drive the malignant behaviour of cancer cells or “weaken” the patient’s immune system and their use has been associated with marked clinical benefits, including improved survival. However, these drugs are expensive, leading many public officials, health care policy experts and oncologists to worry about whether granting access to these drugs will not bankrupt European healthcare.  Yet as critical as this concern may be, a fundamental question must be answered first:  Why are these drugs so expensive?

The skyrocketing cost of new cancer drugs has multiple causes. However, at its core is a shift in the nature of cancer research from being mostly an academic endeavour funded by governments and universities to a largely commercial one funded and conducted by pharmaceutical companies. The reasons for this shift relate ultimately to the complexity and huge cost of conducting cancer research. (2)

From a scientific standpoint, genomic studies have revealed that cancer originating in one organ such as the lungs or the breast is not one disease, but multiple diseases that differ genetically and biologically from one another. Furthermore, a single tumour carries various cancer cell populations; therefore, in any given patient, a drug that kills half of a tumour might do nothing for the rest. Drug candidates must undergo lengthy study before being registered for use, from cell lines and animal models to multiple phases of study in humans. This means that most drug candidates fail before reaching the market, and that successful drugs need to pay for those that fail. Moreover, the complexity of cancer often precludes clear-cut study objectives such as “cure”, and forces the cancer community to choose less ambitious ones, such as temporarily halting progression of disease, or improving symptoms and quality of life.

In designing trials to register new drugs, these objectives translate into needing to study hundreds or even thousands of patients for years before concluding whether a drug is effective. The regulatory burden has also increased expenses in a significant manner, as it demands close patient and hospital monitoring in order to maximize patient safety and minimize fraud. While this is important, it renders modern clinical research too expensive for any one hospital or one country to bear alone, leaving only one stakeholder able to invest the necessary billions:  pharmaceutical companies (Pharma).

Pharma has thus become the inescapable partner for the conduct of “practice-changing” clinical trials. Being privately owned, Pharma has a justifiable financial responsibility towards its shareholders, and this impacts drug development in meaningful ways. Two notable consequences are conservative trial designs and a profusion of “me too” drugs.

In the past, when there was little understanding of cancer heterogeneity, designing trials to answer a very basic question (does the drug work for the average patient?) was scientifically acceptable. Since we now know that any drug given to cancer patients will help only some of them, modern clinical trials should always include a clear strategy to identify those patients.

However, this has the inherent problem of diminishing the number of potential consumers. Pharma therefore often (though not always) opts for conservative designs that stack the odds in favour of  the new drug “succeeding” for the largest possible number of patients and being prescribed for long durations with little scientific rationale. This leads to significant costs for health care systems and subjects many patients to unnecessary drug exposure – and associated side effects. Additionally, the discovery of a new means to attack cancer cells – a therapeutic target – often leads to a “gold rush” as companies look to develop drugs that exploit it. Similar drugs end up being tested in similar settings – in essence the same study is run repeatedly, using up financial resources that could be put to better use, and reducing the likelihood that clinically useful biomarkers of drug response will be discovered.

If Europe is to both fight cancer efficiently and retain its current health care systems, a major reform in drug development is necessary, with “risk sharing” by governments. This is the conclusion drawn by the Breast International Group (BIG) after twenty years of experience in partnering with Pharma for new drug development in breast cancer.

While achieving  a number of successes, such as the HERA study results leading to the European registration of the life-saving drug trastuzumab in 2005 (3) – BIG’s attempts, as an academic research network to better select the patients most likely to benefit from new drugs or to investigate shorter treatment exposures, have largely failed, as they are viewed as too “risky” by Pharma.

How to address this?

Governments can play a decisive role by increasing funding for academic initiatives that could ultimately reduce drug costs and unnecessary exposure of patients to drugs and their side effects. Reducing the regulatory burden by streamlining processes and harmonising them at the EU level is another step in the right direction.  Finally, new anticancer drugs are not all created “equal,” and the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale is a useful instrument that serves three purposes (4):

1) It provides a ranking of new anticancer drugs in relation to their “value” for patients, with the highest scores allocated to drugs that prolong cancer patients’ lives and/or significantly improve their quality of life (even if the latter is often difficult to measure);

2) It should impact the design of future clinical trials and, in particular, promote patient-reported outcomes as well as the selection of more meaningful hazard ratios and absolute gains (in overall survival); and

3) It facilitates the dialogue between physicians and their patients, so that the latter will no longer have unrealistic expectations about the treatment being discussed.

4) Last, but not least, new standards for pricing that take into account the degree of benefit of the drug should be put in place.

References

1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer 2013;49(6):1374–403.

2. Piccart-Gebhart MJ. The 41st David A. Karnofsky Memorial Award Lecture: Academic Research Worldwide–Quo Vadis? J Clin Oncol 2014;32(4):347–54.

3. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353(16):1659–72.

4. Cherny NI, Sullivan R, Dafni U, et al. A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol 2015;26(8):1547–73.