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Chemo, a bad choice for 90% of cancers, BMJ article
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For 90% of cancer patients, chemotherapy is a bad choice, the BMJ article finds!

http://www.bmj.com/content/355/bmj.i5792?utm_medium=email&utm_campaign_name=201611315&utm_source=etoc_daily

JK’s Introduction: This is a very important, though not unique assessment of a grossly overly hyped treatment—true to pharma’s tobacco ethics business model.  At the end of this are JK’s comments on why the picture painted in the article falls significant short of scientific standards.  The authors are forced to rely upon published articles, and those are industry funded which are always positively biased to favor industry.  For more see my after-words at the bottom. 

The journal article approved by one of the 4 top English-language journals drives this point home.     

Analysis

Cancer drugs, survival, and ethics

  • BMJ 2016355 doi: http://dx.doi.org/10.1136/bmj.i5792 (Published 09 November 2016)Cite this as: BMJ 2016;355:i5792   Accepted 24 October 2016

     

    Peter H Wise, former consultant physician and senior lecturer  wisepeter@hotmail.com

Despite considerable investment and innovation, chemotherapy drugs have had little effect on survival in adults with metastatic cancer. Peter Wise explores the ethical issues relating to research, regulation, and practice

Cancer survival has improved in recent decades. Trends in the US show that five year relative survival in adults with solid cancer has increased from 49% to 68% over 40 years.1 There have been important advances in chemotherapy in recent years, including for melanoma, medullary thyroid cancer, and prostate cancer. Immunotherapy, together with targeted and precision (personalised) approaches guided by patient and tumour biomarkers, also produces benefit in subgroups of the more common cancers.2 But how much of the improvement in cancer survival can we attribute to drugs?

 

Survival

A meta-analysis published in 2004 explored the contribution of cytotoxic chemotherapy to five year survival in 250 000 adults with solid cancers from Australian and US randomised trials.3 An important effect was shown on five year survival only in testicular cancer (40%), Hodgkin’s disease (37%), cancer of the cervix (12%), lymphoma (10.5%), and ovarian cancer (8.8%). Together, these represented less than 10% of all cases. In the remaining 90% of patients—including those with the commonest tumours of the lung, prostate, colorectum, and breast—drug therapy increased five year survival by less than 2.5%—an overall survival benefit of around three months.3 Similarly, 14 consecutive new drug regimens for adult solid cancers approved by the European Medicines Agency provided a median 1.2 months overall survival benefit against comparator regimens.4 Newer drugs did no better: 48 new regimens approved by the US Food and Drug Administration between 2002 and 2014 conferred a median 2.1 month overall survival benefit.5 Drug treatment can therefore only partly explain the 20% improvement in five year survival mentioned above. Developments in early diagnosis and treatment may have contributed much more.6

The approval of drugs with such small survival benefits raises ethical questions, including whether recipients are aware of the drugs’ limited benefits, whether the high cost:benefit ratios are justified, and whether trials are providing the right information.  [It is worse than that because industry-funded trials ALWAYS is distorted to favor industry.  The methods of cheating are shocking, and indicate a very broken system of journal reviews—See Prof. Ben Goldacre’s Bad Pharma.  One is way is the washout period.  For example in the Juniper study the statin was  given for 2 months, the volunteers were then called in for blood work, at which time about 30% were dropped out, and then the trial was started.  W ]

Cancer trial concerns

At most 3% of adult cancer patients participate in trials,7 and given the many new drugs and regimens, greater enrolment is a constant aim. Since they are mostly financed by the drug industry, trials can significantly reduce national expenditure on cancer drugs at a time of escalating global costs (around $110bn (£85bn; $95bn) was spent on cancer drugs in 2015).8Trials also allow patients the opportunity of having otherwise unavailable or unaffordable treatment under close supervision of a trial centre, although most studies show that patients do not realise that participating in a trial will primarily benefit others.9 An unethical pressure to enrol is reflected by several studies showing that up to half of patients in cancer drug trials were led to believe that such participation was their only option.9

Furthermore, we cannot infer that the benefits seen in the small number of trial participants will be replicated in the 97% or more outside trial centres, where staffing, procedure, and facilities might be different. Although there are a few reports of similar outcomes in patients inside and outside trials, the uncontrolled nature of those studies and non-homogeneous patient characteristics do not allow a wider scale assumption of similarity.10

[The norm is to select an ideal group of patients who show reduced side effects and better outcome—they are not the real world population.]  Bypassing previous university based trial procedures, pharma now outsources many trials to commercial contract research organisations (CROs), responsible only to the company that hires them. A recent WHO supported Dutch study concluded that many such trials “place patients at ethical risk.”11 [Most of the CRO studies are done in underdeveloped nations with language barriers, which permits more room for tobacco-science trials.[1]] 

The agreed primary response marker of overall survival—the time from drug assignment to death from any cause—is meaningful and, most importantly, understandable by patients. However, to shorten trial duration, minimise the number of trial participants, and enable rapid access of drugs to the market, many trials use surrogate endpoints. These include overall response rate, early tumour shrinkage, and, most commonly, progression-free survival (time from assignment to progressive disease or death from any cause). These endpoints are imaging based and more rapidly available but, with some exceptions, have been shown to correlate poorly with overall survival.12 13

Many drugs approved on the basis of better progression-free survival have been subsequently found not to produce better overall survival than the comparator drug.14 Some of these drugs are logically withdrawn but others remain inexplicably on the market.15

Surrogate endpoints are also used by the FDA and EMA for accelerated and conditional approval, respectively, of what are judged to be urgently needed new drugs. A 2010 FDA review revealed that 45% of cancer drugs given accelerated approvals were not granted full approval, either because subsequent trials failed to confirm effectiveness or because the results of trials were not submitted.16 One reason may be the industry's reluctance to communicate negative results17 (heavy penalties for delayed or absent submission of confirmatory trial results have only recently been introduced). Bearing in mind the usually marginal survival benefits, any haste for approval is only occasionally justified.

The FDA’s decision to introduce a “breakthrough” category in 2012 compounds the risks of premature approval on limited evidence.18 The pressure for early approval is enhanced by lobbying from patient advocacy groups, prompted by industry and with often premature media announcements of drugs that are “game changing,” “groundbreaking,” “revolutionary,” “miracle,” or other unjustifiable superlatives. The risky practice of approval before proof gains even more momentum.

Quality of life assessments increasingly form part of cancer drug trials. However, many evaluations are invalidated by selective use of questionnaire items and time points to demonstrate drug benefit,19 together with frequent “drop out” of patients, inability or refusal to answer questionnaires, and other causes of missing data. Few studies show anything more than small and transient improvements in quality of life from chemotherapy, mostly reflecting temporary tumour shrinkage.  [One standard ploy is last observation carried forward, in which when a patient drops out, no reason for it is given, and the positive results up to the point are carried forward as though the patient completed the trial that they didn’t.]

 

Drug approval

The low threshold of approval (efficacy bar) for these expensive drugs ignores the ethical principle of fairness and equity.20 By promoting treatment of poorly responsive cancers it denies valuable resources to early diagnosis approaches and other health needs. Generous approval may benefit some patients, but it also helps pharma and government to profit. Corporate taxation of 30-35% on cancer industry’s average 22% profit margins on $50bn national drug sales21 yielded the US government alone an estimated $3.8bn in 2015.

In a further doubtfully ethical practice of regulatory capture22 industry attracts former staff from regulatory agencies to help perfect new applications and so smooth their transit.23 Thus the regulator risks being regulated by the industry that it has been appointed to regulate. This so called revolving door phenomenon has proved difficult to eliminate, as is the case with other industry-government interactions.

In England, the National Institute of Health and Care Excellence (NICE) has now taken control of the Cancer Drugs Fund, which enables individual patients to receive funding for drugs not routinely paid for by the NHS.24 The fund had been criticised for poor monitoring of performance, spiralling annual costs (over £300m), and inappropriate approvals. NICE is highly cost aware, and it is to be hoped that a less permissive approval principle will evolve. Evaluations using the European Society of Medical Oncology's clinical benefit scale should also help to clarify ethically important cost-benefit relations25 in order to achieve the same aim.

More post-approval “real world” evaluation of cancer drugs would be an important step forward. Together with industry, the integration of the Cancer Drugs Fund into NICE could facilitate a systematic and highly relevant national assessment of the community’s benefit from cancer drugs.

In low and middle income countries, funding drugs for a rapidly increasing incidence of cancer is even more difficult. With cost:benefit ratios probably even higher, it remains to be seen how valuable the cancer drugs from the World Health Organization’s recently published essential medicines list prove to be.26

 

Inadequate consent

In the US, cancer treatment now represents a major cause of personal bankruptcy.27 Cancer drugs have a greater imbalance of risks and benefits than many surgical procedures and therefore warrant a consent document. However, this is often not issued or signed.28Furthermore, consent is valid only if it relates to the individual information discussed with that patient20—which is usually even less well documented.

There are few data on patients’ awareness of cancer drug [lack of] effectiveness or the incidence and potential severity of their side effects. Many are likely to be unaware of the 80% risk of diverse side effects, of which up to 64% are serious (grades 3-4).29  [This is all the worse since most of those who submit to chemotherapy have  ready been cured by surgery, and if perchance the early stage diagnosis is wrong, and the cancer is metastatic, the chemo won’t change the deadly course of events, except of the 10% of cancers where chemo can save lives].  There is also a drug and disease dependent risk of death from treatment itself, especially in the first month of therapy.30 Nor are patients likely to be informed of the increased risk of dying in hospital compared with patients receiving only supportive care.31 This is important, since studies show that most patients prefer to end their lives in their own homes or hospices rather than in hospital.32Unawareness of poor treatment outcomes leads patients to only rarely question a physician’s proposal for chemotherapy.33

Patients overestimate potential drug benefits. In an important multi-centre study, almost 75% of 1200 patients with metastatic colorectal and lung cancers considered it likely that their cancers would be cured by chemotherapy.34 Yet a cure in these situations is virtually unknown. In another study of decision making discussions about chemotherapy between doctors and patients, survival issues were considered to have been properly covered in only 30%.35 Dutch and Australian studies have found that the option of supportive care is raised in only one quarter of oncologist consultations,33 36 probably because of patient and family expectations of active treatment. Physicians also have competing interests; known to influence the choice of drug and even a decision on whether to treat.37  [The oncologist receives the spread between in clinic billing for drug and the wholesale price they receive, this averages over half of the clinic’s income.]  Yet supportive care can extend life and enhance its quality, especially if introduced early.38

Informed consent is clearly a complex process extending far beyond the signed consent form.39 It should follow discussions based on balanced and fully documented verbal and written information, which perhaps would be more ethically provided by independent trained counsellors less exposed to competing interests.20 Patients should be fully empowered by discussion and subsequent triage to receive cancer drugs, to enrol in a clinical trial, or to accept best supportive care—realising that a decision not to have drug treatment (often referred to pejoratively as refusal) is ethically and morally appropriate.20 In one study of 128 people with lung cancer, around a third of patients wished to share decision making, yet were poorly catered for.40

In search of ethics

Many irregularities and competing interests—in pharma, in trials, in government approval, and in the clinical use of cancer drugs—impact ethically on the care and costs of patients with cancer. Non-representative clinical trials with imprecise endpoints and misinformed patients with unrealistic expectations compel interventions that are mostly not in their best interests. Spending a six figure sum to prolong life by a few weeks or months is already unaffordable, and inappropriate for many of the 20% of the (Western) population who will almost inevitably die from solid tumour metastases.[2] 

Ethical cancer care demands empowerment of patients with accurate, impartial information followed by genuinely informed consent in both the clinical trial and therapeutic settings. Intensified prevention, earlier detection, more prompt and radical treatment of localised and regional disease, together with highly skilled, earlier, supportive care are the important yet underfinanced priorities in cancer control. Ethical impediments to sound practice need to be addressed and corrected. Above all, the efficacy bar for approval needs to be raised for both new and existing cancer drugs41 —by using more meaningful statistical and disease specific criteria of risk-benefit and cost-benefit.25 Finally, aggressively targeting the less than ethical actions of stakeholders in the heavily veiled medical-industrial complex may be the only way forward: current market driven rather than health driven priorities and practices do not benefit cancer patients.

 

Key messages

  • Advances in chemotherapy have contributed little to population cancer survival

  • Responses in clinical trials may not apply to patients treated in the community

  • Evaluation outside trial centres is essential to ensure that scarce resources are not squandered

  • Stricter approval criteria are needed to achieve ethical treatment and reduce cancer costs

  • Ethical informed consent and empowerment of patients must be promoted

Footnotes

  • Contributors and sources: PHW has had a career long involvement with medical ethics, including major responsibilities to research, ethical, and drug evaluation committees at hospital, university and government levels in Australia and the UK. He represented the Royal College of Physicians for many years on the clinical research ethics committee of the Royal College of General Practitioners, London, latterly as its vice chairman. As an endocrinologist and researcher, he has a particular interest in paraneoplastic endocrinopathies, which has brought him into contact with many patients with advanced cancer.



[1]  Two very common examples of tobacco science are washout period and low dose (a bit of information never submitted by pharma in the in write-up of pharma sent to the journals.)   A wash-out period consist of giving the volunteers the two treatments for several weeks, evaluating  the response, then dropping out those who fail to respond or have major side effects.  Since cancers trials do not have a placebo group, a second common ploy used in head-to-head trials is to use a lower than normal dose of the standard drug.  I have only mentioned two; the list of the methods for cheating is long.  Finally progression-free survival and tumor shrinkage often do not translate to benefit in the group of terminal patients in the trial is because the chemotherapy eliminates the susceptible cancer cell lines and thus leaves the more aggressive cancer cells to absorb the available oxygen and glucose. 

[2] This is only the tip of the abuse.  For example of those with stage 1 breast cancer, only around 5% will have in fact metastatic breast cancer and will die of it within 10 years.  However, the majority of stage 1 cancers will be given chemotherapy anyway, even though they have been cured.  Then they will be given an estrogen blocking drug (female castration) most commonly Tamoxifen and this will shorten their and lower its quality—I would estimate 7 years.  

References

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin2015;65:5-29. doi:10.3322/caac.21254 pmid:25559415.

CrossRefMedline

Masters GA, Krilov L, Bailey HH et al. Clinical cancer advances 2015: annual report on progress against cancer from the American Society of Clinical Oncology. JCO, 2014.

Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol (R Coll Radiol)2004;16:549-60. doi:10.1016/j.clon.2004.06.007 pmid:15630849.

CrossRefMedline

Apolone G, Joppi R, Bertele V, et al. Ten years of marketing approvals of cancer drugs in Europe. Br J Cancer2005;93:504-9. doi:10.1038/sj.bjc.6602750 pmid:16136026.

CrossRefMedlineWeb of Science

Fojo T, Mailankody S, Lo A. Unintended consequences of expensive cancer therapeutics—the pursuit of marginal indications and a me-too mentality that stifles innovation and creativity: the John Conley Lecture. JAMA Otolaryngol Head Neck Surg2014;140:1225-36. doi:10.1001/jamaoto.2014.1570 pmid:25068501.

CrossRefMedline

Hiom SC. Diagnosing cancer earlier: reviewing the evidence for improving cancer survival. Br J Cancer2015;112(Suppl 1):S1-5. doi:10.1038/bjc.2015.23 pmid:25734391.

CrossRefMedline

Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA2004;291:2720-6. doi:10.1001/jama.291.22.2720 pmid:15187053.

CrossRefMedlineWeb of Science

Constantino T. Global market for cancer treatments grows to $107 billion in 2015. 2 Jun 2016. https://www.imshealth.com/en/about-us/news/ims-health-study-global-market-for-cancer-treatments-grows-to-107-billion-in-2015-fueled-by-record-level-of-innovation.

Nurgat ZA, Craig W, Campbell NC, Bissett JD, Cassidy J, Nicolson MC. Patient motivations surrounding participation in phase I and phase II clinical trials of cancer chemotherapy. Br J Cancer2005;92:1001-5. doi:10.1038/sj.bjc.6602423 pmid:15770219.

CrossRefMedlineWeb of Science

Peppercorn JM, Weeks JC, Cook EF, Joffe S. Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review. Lancet2004;363:263-70. doi:10.1016/S0140-6736(03)15383-4 pmid:14751698.

CrossRefMedlineWeb of Science

Van Huijstee M, Schipper I. Ethical concerns. In: Putting contract research organisations on the radar.Social Sciences Research Network, 2011: 55-72.

Prasad V, Kim C, Burotto M, et al. The strength of association between surrogate endpoints and survival in oncology. JAMA Intern Med2015;175:1389-98. doi:10.1001/jamainternmed.2015.2829 pmid:26098871.

CrossRefMedline

Wilson MK, Collyar D, Chingos DT, et al. Outcomes and endpoints in cancer trials: bridging the divide. Lancet Oncol2015;16:e43-52. doi:10.1016/S1470-2045(14)70380-8 pmid:25638556.

CrossRefMedline

Kim C, Prasad V. Strength of validation for surrogate end points used in the US Food and Drug Administration's approval of oncology drugs. Mayo Clin Proc2016;91:713-25. doi:10.1016/j.mayocp.2016.02.012.

CrossRef

Nabors LB. The role of bevacizumab in glioblastoma. J Natl Compr Canc Netw2014;12:1201-2.pmid:25190689.

FREE Full Text

Johnson JR, Ning Y-M, Farrell A, Justice R, Keegan P, Pazdur R. Accelerated approval of oncology products: the food and drug administration experience. J Natl Cancer Inst2011;103:636-44. doi:10.1093/jnci/djr062 pmid:21422403.

Abstract/FREE Full Text

Wise P, Drury M. Pharmaceutical trials in general practice: the first 100 protocols. An audit by the clinical research ethics committee of the Royal College of General Practitioners. BMJ1996;313:1245-8. doi:10.1136/bmj.313.7067.1245 pmid:8939118.

Abstract/FREE Full Text

Darrow JJ, Avorn J, Kesselheim AS. New FDA breakthrough-drug category--implications for patients. N Engl J Med2014;370:1252-8. doi:10.1056/NEJMhle1311493 pmid:24670173.

CrossRefMedlineWeb of Science

Joly F, Vardy J, Pintilie M, Tannock IF. Quality of life and/or symptom control in randomized clinical trials for patients with advanced cancer. Ann Oncol2007;18:1935-42. doi:10.1093/annonc/mdm121 pmid:17698837.

Abstract/FREE Full Text

English V, Sommerville A, Brannan S. Medical ethics today. Blackwell, 2012.

QuintilesIMS Institute. Global oncology trend report. 2016. http://www.imshealth.com/en/thought-leadership/quintilesims-institute/reports/global-oncology-trend-report-a-review-of-2015-and-outlook-to-2020

Abraham J. The pharmaceutical industry as a political player. Lancet2002;360:1498-502. doi:10.1016/S0140-6736(02)11477-2 pmid:12433532.

CrossRefMedlineWeb of Science

Bien J, Prasad V. Future jobs of FDA’s haematology-oncology reviewers. BMJ2016;354:i5055. doi:10.1136/bmj.i5055 pmid:27677772.

FREE Full Text

NICE/NHS. Proposals for a new Cancer Drugs Fund (CDF) operating model. 2015. https://www.engage.england.nhs.uk/consultation/cdf-consultation

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 Oncol2015;26:1547-73. doi:10.1093/annonc/mdv249 pmid:26026162.

Abstract/FREE Full Text

Shulman LN, Wagner CM, Barr R, et al. Proposing essential medicines to treat cancer: methodologies, processes and outcomes. J Clin Oncol2016;34:69-75. doi:10.1200/JCO.2015.61.8736 pmid:26578613.

Abstract/FREE Full Text

Zafar SY, Peppercorn JM, Schrag D, et al. The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient’s experience. Oncologist2013;18:381-90. doi:10.1634/theoncologist.2012-0279 pmid:23442307.

Abstract/FREE Full Text

Weingart SN, Flug J, Brouillard D, et al. Oral chemotherapy safety practices at US cancer centres: questionnaire survey. BMJ2007;334:407. doi:10.1136/bmj.39069.489757.55 pmid:17223629.

Abstract/FREE Full Text

Chan JK, Kiet TK, Monk BJ, et al. Applications for oncologic drugs: a descriptive analysis of the oncologic drugs advisory committee reviews. Oncologist2014;19:299-304. doi:10.1634/theoncologist.2013-0276 pmid:24599479.

Abstract/FREE Full Text

Wallington M, Saxon EB, Bomb M, et al. 30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study. Lancet Oncol2016;17:1203-16. doi:10.1016/S1470-2045(16)30383-7 pmid:27599138.

Wright AA, Zhang B, Keating NL, Weeks JC, Prigerson HG. Associations between palliative chemotherapy and adult cancer patients’ end of life care and place of death: prospective cohort study. BMJ2014;348:g1219. doi:10.1136/bmj.g1219 pmid:24594868.

Abstract/FREE Full Text

Higginson IJ, Sen-Gupta GJ. Place of care in advanced cancer: a qualitative systematic literature review of patient preferences. J Palliat Med2000;3:287-300. doi:10.1089/jpm.2000.3.287 pmid:15859670.

CrossRefMedline

Gattellari M, Voigt KJ, Butow PN, Tattersall MH. When the treatment goal is not cure: are cancer patients equipped to make informed decisions?J Clin Oncol2002;20:503-13. doi:10.1200/JCO.20.2.503 pmid:11786580.

Abstract/FREE Full Text

Weeks JC, Catalano PJ, Cronin A, et al. Patients’ expectations about effects of chemotherapy for advanced cancer. N Engl J Med2012;367:1616-25. doi:10.1056/NEJMoa1204410 pmid:23094723.

CrossRefMedlineWeb of Science

Audrey S, Abel J, Blazeby JM, Falk S, Campbell R. What oncologists tell patients about survival benefits of palliative chemotherapy and implications for informed consent: qualitative study. BMJ2008;337:a752. doi:10.1136/bmj.a752 pmid:18669570.

Abstract/FREE Full Text

Koedoot CG, Oort FJ, de Haan RJ, Bakker PJ, de Graeff A, de Haes JC. The content and amount of information given by medical oncologists when telling patients with advanced cancer what their treatment options are. palliative chemotherapy and watchful-waiting. Eur J Cancer2004;40:225-35. doi:10.1016/j.ejca.2003.10.008 pmid:14728937.

CrossRefMedlineWeb of Science

Malin JL, Weeks JC, Potosky AL, Hornbrook MC, Keating NL. Medical oncologists’ perceptions of financial incentives in cancer care. J Clin Oncol2013;31:530-5. doi:10.1200/JCO.2012.43.6063 pmid:23269996.

Abstract/FREE Full Text

Bauman JR, Temel JS. The integration of early palliative care with oncology care: the time has come for a new tradition. J Natl Compr Canc Netw2014;12:1763-71, quiz 1771.pmid:25505216.

Abstract/FREE Full Text

Hall DE, Prochazka AV, Fink AS. Informed consent for clinical treatment. CMAJ2012;184:533-40. doi:10.1503/cmaj.112120 pmid:22392947.

FREE Full Text

Pardon K, Deschepper R, Vander Stichele R, et al. Are patients’ preferences for information and participation in medical decision-making being met? Interview study with lung cancer patients. Palliat Med2011;25:62-70. doi:10.1177/0269216310373169 pmid:20621948.

Abstract/FREE Full Text

Ellis LM, Bernstein DS, Voest EE, et al. American Society of Clinical Oncology perspective: raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol2014;32:1277-80. doi:10.1200/JCO.2013.53.8009 p

 

 

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Afterword

It is worse than that, they are over overly optimistic:  1) doesn’t consider long-term survival—past 5 years, 2) the reduced quality of life, 3)  short-term suffering associated with chemo, 4) and that industry funded studies always favors industry (positive bias).  It starts with journal articles façade review:  they don’t receive the raw data, only the industry writes of the clinical trial or experiment.  For the common ways they cheat read Ben Goldacre’s “Bad Pharma” or click on my assessments at side effects and marketing science.  Over to-thirds of patients do not have metastatic cancer, and thus excision has assured their survival; thus the chemotherapy being of no benefit only harms these patients who had their cancer cut out.  And those who have adjacent cancer remaining that is indolent, the chemo won’t affect the course of events.  Merely shrink a cancer (the commonly used surrogate endpoint) entails the proliferation of the cancer cells that are resistant to the chemotherapy.  Remember that a cancer tumor has a high rate of mutation, thus it consist of a diverse group of cells. Making dormant or killing some of those cells assures that the worst of them survive and not competing with less aggressive cells for nutrients and oxygen.  This helps to explain why pharma normally compares in phase III trial the new drug to an older treatment (often at less than optimal dose) rather than those who refuse treatment to the treatment.       

I would not confuse “survival”, which typically is measured in weeks of longer life with “cure.  Survival” is used by the oncologist to sell their in-office chemo treatment does not mean “cure”.  Those without metastatic cancer are cured by excision, and if the some cancer is missed, the chemo does not have the ability to destroy the remaining cancer.  The norm is for the chemo to be given in the clinic, thus the clinic profits from the spread between what they bill insurance and Medicare and the wholesale price of the chemo. This explains why oncologists will often require chemo prior excision—more pressure upon the patient to submit.  Business is profit driven. 

 

 

 

 

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Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment. 

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