BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h2068 (Published 23 April 2015)Cite this as: BMJ 2015;350:h2068

Donald W Light, professor and Joel Lexchin, professor 

Rushed approvals result in a poor deal for both patients and cancer research

Unlike most other diseases, cancer instils a special fear and “is treated as an evil, invincible predator, not just a disease.”

The ability of drug companies to charge very high prices, even when most approved cancer drugs provide little gain for patients, drives much of the research, as desperate patients lead some governments and private insurers to pay whatever companies charge.

Officials within the US Food and Drug Administration are enthusiastic about new cancer drugs. Richard Pazdur, who oversees oncology activities for the FDA says that new cancer drugs are so effective that “We don’t have a lot of questions on [these] drugs because they’re slam dunks. It’s not if we’re going to approve them. It’s how fast we’re going to approve them.”

The methodological weaknesses in oncology trials do not support such enthusiasm.

Trials for cancer drugs were 2.8 times more likely not to be randomised, 2.6 times more likely not to use a comparator (single arm), ….

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From http://www.sciencedaily.com/releases/2015/05/150507135917.htm: Highly priced cancer drugs get rushed approvals despite poor trial methodology and little effect on the longevity of patients, cautions York University Professor Dr. Joel Lexchin in the School of Health Policy and Management.

“Patients and their doctors should demand that regulators require pharma companies to provide clear evidence of clinical effectiveness of the drugs, resulting from rigorous methodology,” suggests Lexchin. “Drug agencies like the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) don’t actually look at whether people live longer.”

In an article in the British Medical Journal, titled “Why do cancer drugs get such an easy ride?,” Lexchiin and co-author Donald Light, a professor in the School of Osteopathic Medicine, Rowan University in New Jersey, note that accelerated approval and shortened review times also make it a smooth sail for cancer drugs.

Lexchin cites earlier research reviewing solid cancer drugs within 10 years of EMA approval to point out that these drugs improved survival by just over a month.

“Similarly 71 drugs approved by the FDA from 2002 to 2014 for solid tumours have resulted in median gains in progression-free and overall survival of only 2.5 and 2.1 months, respectively,” he says adding, “Also, only 42 per cent met the American Society of Clinical Oncology Cancer Research Committee’s criteria for meaningful results for patients.”

From: http://www.yourhealthbase.com/ihn260.pdf: How Effective Are Newer Chemotherapy Drugs?

• An editorial in the April 23, 2015 British Medical Journal examined the recent accelerated drug approval process for cancer drugs in both the US and Europe. The subtitle was “Rushed approvals result in a poor deal for both patients and cancer research.”
• This editorial contains some extremely disturbing statistics and information the authors obtained from reviewing the chemotherapy clinical study literature and other papers over the last 8 to 10 years.
• Between 2007 and 2010, … almost 9000 oncology clinical drug trials were compared with trials for other diseases, the former were 2.6 times more likely not to use a comparator and 1.8 time more likely not be blinded (open to bias from the investigators) … this undermine the validity of the outcomes, it also reflect what regulators will allow. (In lay man language this means bad research. And the regulators — FDA, allows that!).
• The European Medicine Agency … found that new oncology drugs improved survival by a mean of 1.5 months and a median of 1.2 months.
• The 71 drugs approved by the US FDA from 2002 to 2014 for solid tumors have resulted in median gains in progression-free survival of 2.5 months and overall survival of 2.1 months. (Pay thousands of ringgit plus suffer side effects and you live 2.5 months longer? Not cured? As you told about this before you started paying though your nose?).
• Post-marketing changes in the package insert (so-called label) were substantially greater for oncology drugs given priority approval as compared to those going through the much longer standard process, which the authors suggest reflects deficiencies in the accelerated review process. (In layman language it means, quicky, sloppy job — a rush to make quick bucks?)
• Both the European and US regulators allow companies to test cancer drugs using a surrogate endpoint rather than survival or other more patient-centered outcomes. Tumor size is given as an example of an unreliable endpoint since it is highly variable in predicting overall survival. (In layman language the measure of trial outcome is not reliable. Just making the size of tumor smaller — or tumour shrinkage — may not mean anything. Surely it does not mean the cancer is cured! So, the measure of effectiveness is faulty).
• In 2013, two peer-reviewed papers appeared where a total of over 100 oncologists protested against the high prices being charged for cancer drugs when 11 out of 12 approved in 2012 provided only small benefits for patients. (Do you realize that chemo drugs are getting more expensive …the prices of the newer drugs are beyond our imagination. But are they effective? Yes, make you live longer by 2 or 3 months????? But patients want a CURE)
• The authors term the approval process an “Easy Ride” and suggest that this serves both patients and research badly.
• It can also be argued that the majority of cancer drug development research currently leading to new drug approval is bogged down in merely getting more ineffective drugs approved in the hope that marginal improvements in survival will lead to enhanced profits. (The root of this evil is greed! They go after your cancer or after your money?)
• … generally priced so high that the choice is between bankruptcy or declining treatment except for the wealthy.
• The results discussed above are consistent with those presented in 2004 by Morgan et al14. Based on reports from Australia between 1992 and 1997, the contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults was 2.3% whereas in the US it was 2.1%. These results suggest that over this period in these two countries chemotherapy made little contribution to cancer survival. (Yes, they tell you … chemo will give 60% chance, 99% chance, bla, bla …the Australian showed chemo is only 2 or 3% effective).
• Furthermore, not much appears to haves changed between 1992 and 2014 from the patient’s perspective. It is important to note that we are talking about cancers that involve solid tumors. (Why change or improve? As it is – the drug companies are happy, hospitals and doctors are happy! And patients believe and trust them!)
• BOTTOM LINE: When offered one of the new “wonder” chemotherapeutic drugs, it is important to ascertain the actual expected life extension in order to weigh this against the side effects. Trivial life extensions are sufficient to gain regulatory approval and allow patients to be told the treatment will extend their life. Unless carefully qualified, such an approach appears unethical.