Research misconduct rife in Clinical Trials

A major study from New York Institute of Journalism member Charles Seife, M.S has reported that nearly half of the clinical trials approved by the FDA in the USA (which is a gateway for UK approvals) had ‘significant departures’ from accepted standards – these included under-reporting of adverse events, violations of recruitment guidelines, inadequate record keeping, failure to respect the safety, welfare and rights of patients, institutional review board oversights and violations of best practice protocols.

Within the overall picture, the FDA reported on 57 trials of which 22 contained data that was falsified (nearly 40 per cent).

So much for rigorous testing.

Ref: http://archinte.jamanetwork.com/article.aspx?articleID=2109855

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Burzynski – it’s all over now, surely?

A strange situation exists in America that is exploited by several top Cancer Hospitals: Take MD Anderson and Virotherapy or The Preston Robert Tisch Cancer Centre at Duke and Dendritic cell therapy. Both these treatments have some clinical evidence behind them to show there is potential. But, truthfully, that’s about all. So, when all other treatments fail, a phase III clinical trial is set up to give these therapies a whirl. And in some cases they have met with great success. Importantly, the ‘trial’ is well documented, even when people die.

The same ‘methodology and logic’ has been exploited by controversial Doctor Stanislaw Burzynski. The FDA gave some credibility to antineoplastons (complex peptides and peptide mixtures that seemed to be missing in cancer patients) and after nearly 20 years of fighting between the FDA and/or The Texas Medical Board and Burzynski, a lull in the storm saw Burzynski reach for the phase III clinical trial gambit, and continue to treat cancer patients at his clinic. The background to all this can be found here.)

But. Following a Panorama Programme where Burzynski refused to provide results to date saying the FDA forbade it, and the FDA saying he could provide data, I wrote several times to the Burzynski Clinic for clarification. Like Panorama, I received no satisfactory response.

Worse was then uncovered – An analysis of work to date seems to show that with several dozen phase II clinical trials started, he never published a completed phase II trial, although there have been a couple of preliminary reports.

A step change occurred in 2012, with an apparent treatment-related death of a child and this led the FDA to issue a partial clinical hold on the Burzynski Clinic, preventing him enrolling any new children on his clinical trials, although he could keep treating existing patients and enroll new adult patients.

This ‘hold’ was later extended to new adults when the FDA arrived to investigate the clinic. The result of the investigations? More bad news for Burzynski when he received a warning letter from the FDA. That warning covered issues such deficiencies in the Burzynski institutional review board (IRB), the committee responsible for making sure that the clinic falls in line with regulations designed to protect human subjects during ‘research’ (for example, by maintaining adequate documentation covering the functions and operations of the IRB.

This, to some, may just seem like a lack of red tape provisions. But these are supposed to be randomized clinical trials of human beings and the Burzynski clinic needs to be as meticulous as any drugs company, perhaps more so given previous controversies. What seems to have been happening is that the Burzynski has been using what are ‘expedited reviews’. However, taking single patient protocols for an investigational drug that is not FDA-approved does not fall into any of the categories for which expedited review is appropriate, particularly when so many of the patients involved are children.

But the question still remains – Let’s see the results.

And not just the positive ones; what about side-effects like hypernatremia? Again the FDA have presented two new reports and these include statements such as ‘Failure to monitor the progress of an investigation’ and ‘an investigation was not conducted in accordance with the signed statement of investigator and investigational plan’ and ‘failure to prepare or maintain adequate case histories with respect to observations and data pertinent to the investigation’.

All I can conclude from this is that we are very unlikely to get proper clinical trial data at all.

But it gets worse. The FDA noted that
1. ‘You did not have a QA monitor properly monitor CRFs [case report forms] and subject records’
2. ‘The investigator destroyed critical subject case history records (target tumor measurement worksheets) or misplaced case history records (original subject CRFs) for all subjects’
3. ‘Your MRI tumor measurements initially recorded at baseline and on-treatment MRI studies for all study subjects were destroyed and are not available for FDA inspectional review’
4. ‘You failed to monitor as required by Section 16 of your Monitoring Plan. The investigator did not report adverse events (AEs) experienced by study subjects, including 18 cases of hypernatremia’, and (worse still)
5. ‘You failed to protect the rights, safety, and welfare of subjects under your care – Forty-eight (48) subjects experienced 102 investigational overdoses between January 1, 2005 and February 22, 2013, according to the Weekly List of Hospitalizations/SAE [REDACTED] Overdose [redacted]/Catheter Infection report. There is no documentation to show that you have implemented corrective actions during this time period to ensure the safety and welfare of subjects’.

We last amended the write up in CANCERactive on Antineoplastons and The Burzynski Clinic after the Panorama report. At that time we asked ‘Where are the results?’ We shall shortly be revising it all again.

At CANCERactive we do not believe it correct to ignore ‘alternative’ cancer treatments. We try to explain what they are and what they are supposed to do, with research when it exists, but pointing out clearly if none exists. But the fact is the NCI has a review on its website about antineoplastons and the review seems positive. Wikipedia, even today, is surprisingly balanced. So, we will continue to tell patients what this is supposedly all about, but we will now answer our own question: Where are the results? And the answer is ‘Nowhere’.

People touched by cancer who contemplate spending large amounts of money to go to the Burzynski Clinic need to be absolutely clear on this latest information and factor it in to their decision making process.

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Yet another study casts doubts, this time, on ‘landmark’ cancer drug clinical trials

The recent study from researchers C. Glenn Begley and Lee Ellis is the third study in as many years to question the validity of some drug clinical trials. These researchers found that a mere 11 percent of 53 papers on cancer published in reputable, peer-reviewed journals was solid, while the other 89 percent could not be reproduced, implying that it may be false or at the very least misleading.

“The scientific community assumes that the claims in a preclinical study can be taken at face value – that although there might be some errors in detail, the main message of the paper can be relied on and the data will, for the most part, stand the test of time,” wrote the authors about their findings. “Unfortunately, this is not always the case.”

Worse, the 53 published papers on cancer were all considered to be ‘Landmark’ studies yet Begley and Ellis discovered that only six of them could be reproduced and confirmed in a clinical setting.

“[I]t looks like the scientific literature is contaminated with a growing number of tainted studies, which may reach 89 percent, the results of which are not reproducible by any means,” writes Eleni Roumeliotou for GreenMedInfo.com about the shocking findings. “This means that to an extent, we have based our healthcare and clinical guidelines on fake studies that reported untruthful results in order to accommodate the interests of industrial corporations.”

In a second study, this time by University of Michigan Dr. Reshma Jagsi, M.D,at least 17 per cent of research studies had serious conflicts of interest – they were not independent but following Pharmaceutical Company funding, research results were influenced in a pre-determined direction.

“Given the frequency we observed for conflicts of interest and the fact that conflicts were associated with study outcomes, I would suggest that merely disclosing conflicts is probably not enough,” said Dr Jagsi. “It’s becoming increasingly clear that we need to look more at how we can disentangle cancer research from industry ties.”

For the full story, go to

http://www.naturalnews.com/040230_cancer_research_false_conclusions.html#ixzz2Sb6y1AUs

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Corruption endemic in medicine chain, according to WHO

‘Corruption in the pharmaceutical sector occurs throughout all stages of the medicine chain, from research and development to dispensing and promotion’.

‘A lack of transparency and accountability within the medicines chain can also contribute to unethical practices and corruption’.

Unethical practices such as bribery, falsification of evidence, and mismanagement of conflicts of interest are ‘common throughout the medicine chain.’

These statements are all contained in a fact sheet from the World Health Organisation. The medicine chain refers to each step involved in getting drugs into the hands of patients, including drug creation, regulation, management and consumption. The report suggests a number of other concerns, for example: Clinical trials may be conducted without proper regulatory approval, royalties may be collected through manipulation or disregard of the patent system, corruption can also occur during the drug inspection process, products may be registered with incorrect or insufficient information and drugs may be produced through substandard or counterfeit methods. (www.naturalnews.com; www.who.int 2010)

For another piece on falsified research in cancer Click Here.

Link (http://www.canceractive.com/cancer-active-page-link.aspx?n=3190&Title=Cancer%20Watch%20May%202012%20%28Another%20Cancer%20Researcher%20tells%20of%20falsified%20drug%20research%29)

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The scandal that kept an alternative cancer therapy from a fair evaluation

When a pharmaceutical company wants to put a new drug through clinical trials, by and large three things happen:

1) They select a team of scientists if they don’t have such a team already on their payroll

2) The scientists then select the patients that will be part of the trial. The selection process can involve very detailed screening tests to avoid anyone who might negatively influence a good result.

3) When the trial has been completed, the research report is handed over to the pharmaceutical company, who can review the data and will massage the results in their Press Releases.

Unfortunately, none of this happens when a promising ‘alternative’ therapy is tested in Clinical Trials. And what happened to the evaluation of the Gonzalez Therapy was nothing short of scandalous.

We have covered the theories of Beard, the work of Kelly and the work of Dr Nicholas Gonzalez in his New York Clinic at CANCERactive several times (CLICK THIS LINK to go to an article on his work http://www.canceractive.com/cancer-active-page-link.aspx?n=469 )

Gonzalez has treated a number of cancers with success at his clinic since 1990. He even took part in a preliminary Clinical Trial when his nutritional Therapy (which involves a  tailor made package of supplements and pancreatic enzymes) was tested using pancreatic cancer patients. In a letter to me, Gonzalez wrote, “We did complete a trial of our therapy with patients diagnosed with pancreatic cancer, supervised by the National Cancer Institute and funded by Nestle. The results of that study were published in the peer reviewed journal Nutrition and Cancer and reported the best results ever in the treatment of the disease.

As a result of that data, our US National Cancer Institute funded a large-scale clinical trial, which turned out to be, unfortunately, a nightmare of mismanagement. A paper was published a year ago without our knowledge claiming our therapy didn´t work, but the paper was a complete misrepresentation of the large scale clinical trial. I have written a lengthy rebuttal of the recently published article on our website at: http://www.dr-gonzalez.com/jco_rebuttal.htm.”

Now Gonzalez has gone further; he has written a book: ‘What went wrong – The Truth Behind the Clinical Trial of the Enzyme Treatment of Cancer’.

Dr Paul J Rosch, Clinical Professor of Medicine and Psychiatry, New York Medical School writes about the book of the trial as follows:

‘This book is about a $1.4 million grant awarded by the National Cancer Institute in 1998 to do a controlled clinical trial comparing the chemotherapeutic drug Gemzar to Dr Gonzalez enzyme approach in the treatment of patients with pancreatic cancer. Dr Gonzalez documents how the study was mismanaged, how he had no control over the selection of patients, and how the protocol was violated in numerous ways that were subsequently confirmed by regulatory authorities. Nevertheless, a misleading article was published without his knowledge and none of the responsible parties were (sic) ever admonished or held accountable. This tragic tale tends to support a growing suspicion that the cancer cartel of organizations, government agencies and vested interests is devoted more to preserving their enormous profits and reputations than to the prevention and cure of cancer’.

‘What went Wrong’ by Dr Nicholas J Gonzalez is published by New Spring Press.

Dr Gonzalez can be contacted via http://www.dr-gonzalez.com/index.htm

 CANCERactive has no financial links to Dr Gonzalez or his clinic. CANCERactive provides information on cancer treatments so that people with cancer can make better-informed personal choices and so increase their personal odds of survival.

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Having read a report of the Dartington Debate which took place recently on the subject of Integrated Medicine, I was interested to read that some of the assembled gathering concluded that the only treatments that they would consider were those that had passed the ultimate medical gold standard test: The randomised, double blind, placebo controlled Clinical Trial. These people are sadly living in cloud cuckoo land.

First, for those of you that don’t know the term let me explain. This Clinical Trial involves two identical groups of people, one group taking the test treatment, the other taking a ‘placebo’ – an identical injection or pill just containing sugar. It is blind, because the recipients don’t know which they are receiving.

The test is double blind because the scientist doesn’t know which he is giving to whom either. And finally, it is randomised because a computer has assigned the people to each group in a matched way, but randomly.

An unequal playing field

This sort of test, according to Pharmaceutical companies, is very, very expensive to run. And thus it is very, very unlikely that any purveyor of a herb or vitamin would ever have the money to run such a test. Last year Astra Zeneca made over $8.6 billion in profit. The entire supplements industry in the UK was worth peanuts compared to that figure. I know of only one such UK ‘supplements’ test in the last year or so – A Leeds University Clinical Trial on concentrated fish oil omega 3 with pre-cancerous colon polyps (it worked and reduced the size of the polyps). This level of Clinical Trial demands serious funding, something simply beyond the means of the supplements companies – face facts!

Another reason that natural compounds and supplements are ruled out is because the drug companies are unlikely to help. The Leeds University trial prepared the omega-3 as if it were a drug, but others aren’t so fortunate. Professor Robert Thomas of Addenbrooks has been working with newly diagnosed prostate cancer patients and noted that those who followed a programme of broccoli and tomato consumption plus daily exercise pushed the evil date for surgery further into the future. To make any claims he needed to prove this observation scientifically and so he started to dry his broccoli and tomatoes. Ah, but if you want to do a proper trial you need to prepare them in pill form, so they are now classified as drugs and require a drugs company to prepare them. How easy do you think it is to get a drugs company to help with a test on natural compounds which can reduce the usage of their profitable drugs?

These anomalies would only be resolved in the UK if we had a properly Government-funded Institute of Complementary Health as they do in the USA. This needs to include someone responsible collating the information and providing guidelines.

Dubious selection criteria

You may feel that the ‘randomised’ selection process in the randomised, double blind, placebo-controlled test is fool-proof. You’d be completely wrong. New drugs tend to be compared against existing treatments which are used by the sick in all shapes, sizes, ages, smokers and non-smokers and so on. For the new Clinical Trials however, the participating company may well insist that the scientist rule out anybody who may have had a negative reaction in a previous trial, obese people, people with heart problems or anything that might jeopardise a good result. Thus the Clinical Trial can be a random sample chosen from a selected sample. Often a drug trial is conducted with young, healthy people (you’ve probably heard the radio ads recruiting volunteers) with 75 per cent of the volume of the resultant drug used by sick over 65 year olds, who will have a significantly different biochemical profile.

So let’s rule out all those treatments that haven’t passed this gold standard

Well of course curcumin as a preventative cancer treatment is ruled out. But then so are most statins – including those for the seemingly healthy to avoid unexpected heart attacks. But Doctors recommend the statins, don’t they?

Actually, come to mention it, about 95 per cent of drugs in use today would be ruled out, not just complementary and alternative therapies.

Two thirds of cancer patients have surgery but there has never been a randomised, double blind, placebo controlled Clinical Trial on any of it. And increasingly there is evidence that surgery may even spread cancer (See: http://www.canceractive.com/cancer-active-page-link.aspx?n=2976)

Next time your Doctor offers you a drug, ask him if it has been through a randomised, double blind, placebo controlled Clinical Trial and see what he says. If it is a serious condition it is very likely that he will want to give you three or four drugs. Don’t even bother asking about whether the combination has passed the gold standard test. As a cocktail it is almost certain not to have done, which may explain, in part, why prescription drugs are now the highest cause of death in states like Florida with a higher incidence of older people.

Level of evidence?

If, like me you believe that ‘research is for the guidance of wise men and the obedience of fools’, you may consider that there is actually enough evidence to warrant all of the over-50’s in the UK being offered statins along with overweight kids too. As a doctor you may feel the evidence is enough, even if all the Dartington audience using their gold standard filter may not have agreed.

But if you feel it is enough and you offer statins to all, why not consider telling people with pre-cancerous colon conditions about fish oils or curcumin? Both are known to help prevent colon cancer – the former also has Clinical Trials, the latter has a stack of evidence on its side and is even being used as a treatment in some US cancer hospitals.

Why do oncologists offer surgery at the outset of cancer yet they don’t think to offer immune boosting herbs like astragalus or supplements like resveratrol and grape seed extract, which do have good supporting evidence behind them?

Why do some oncologists even criticise cancer patients when they correct their diets? The research is quite clear; ‘overwhelming’ according to the American Cancer Society. Diet and exercise can increase survival times.

A clear legal duty

Only recently we had two women in a week tell us that their oncologist had refused to discuss complementary therapies with them as ‘He may get struck off’. Actually the opposite is true. Your oncologist has a legal duty to inform you fully of all your treatment options. Omitting treatments deliberately is illegal. Ignorance is no defence. Oncologists had better start wising up on complementary and alternative therapies fast. The patient backlash is just around the corner.

The sting?

As part of my preparation for this article, I looked up the ‘randomised, double blind, placebo-controlled Clinical Trial’ on my Internet search engine. Five of the top six listings were definitions but one was actually a trial for a treatment. Here it is. Unfortunately I think some of the ‘skeptic’ attackers of complementary medicine at Dartington might find it a little embarrassing:

Efficacy of a complex homeopathic medication (Sinfrontal) in patients with acute maxillary sinusitis: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial.

 

Zabolotnyi DI, Kneis KC, Richardson A, Rettenberger R, Heger M, Kaszkin-Bettag M, Heger PW.
Source
Research Institute for Ear, Nose, and Throat Diseases, Kiev, Ukraine.
 

Abstract
BACKGROUND:
There is a demand for clinical trials that demonstrate homeopathic medications to be effective and safe in the treatment of acute maxillary sinusitis (AMS).
OBJECTIVE:
The objective of this clinical trial was to demonstrate the efficacy of a complex homeopathic medication (Sinfrontal) compared with placebo in patients with AMS confirmed by sinus radiography.
DESIGN:
A prospective, randomized, double-blind, placebo-controlled, phase III clinical trial was conducted for a treatment period of 22 days, followed by an eight-week post treatment observational phase.
INTERVENTIONS:
Fifty-seven patients received Sinfrontal and 56 patients received placebo. Additionally, patients were allowed saline inhalations, paracetamol, and over-the-counter medications, but treatment with antibiotics or other treatment for sinusitis was not permitted.
MAIN OUTCOME MEASURES:
Primary outcome criterion was change of the sinusitis severity score (SSS) from day zero to day seven. Other efficacy assessments included radiographic and clinical cure, improvement in health state, ability to work or to follow usual activities, and treatment outcome.
RESULTS:
From day zero to day seven, Sinfrontal caused a significant reduction in the SSS total score compared with placebo (5.8 +/- 2.3 [6.0] points vs 2.3 +/- 1.8 [2.0] points; P < .0001). On day 21, 39 (68.4%) patients on active medication had a complete remission of AMS symptoms compared with five (8.9%) placebo patients. All secondary outcome criteria displayed similar trends. Eight adverse events were reported that were assessed as being mild or moderate in intensity. No recurrence of AMS symptoms occurred by the end of the eight-week post treatment observational phase.
CONCLUSION:
This complex homeopathic medication is safe and appears to be an effective treatment for acute maxillary sinusitis.
PMID:
17362845
[PubMed - indexed for MEDLINE]

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