On 2004-04-22 Philip Waddington of Health Canada's Natural Health Products Directorate testified before the Standing Committee on Health. Although his testimony was mainly concerned with Private Member Bill C-420, because EmPowerPlus had been adopted as a poster child of sorts to promote deregulation of natural health products, Dr. Waddington was inevitably asked about Health Canada's enforcement actions against Dr. Kaplan's unapproved research testing EmpowerPlus at the University of Calgary. His testimony is disturbing because it doesn't agree with documents released by Health Canada through ATI, e.g., the agency's correspondence demanding termination of the unapproved placebo controlled RCT on subjects diagnosed with bipolar disorder.
Dr. Waddington made the following statement to the Standing Committee on Health:
And to be clear, when you used the term 'shut down', the trial wasn't so much shut down. What Health Canada said is the people who are currently on it should continue, but you should not bring new people on to it until you've come into compliance with the regulations. People weren't taken off the program they were on. They weren't engaging new people as they went forward.
Source: 37th Parliament, 3rd Session: Standing Committee on Health, Evidence. 2004-04-22. Accessed on 2006-11-29 at: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=80774
This is difficult to reconcile with Health Canada's directive addressed to Dr. Ian Mitchell at the University of Calgary Office of Medical Bioethics. In addition to terminating the clinical trial, Health Canada directed that:
… the sponsor must ensure that these subjects are assessed and their care is transferred to an appropriate professional who can place them on standard therapy.
Source: Akoury M. Health Canada letter to Ian Mitchell with attached document, Information Request to Bonnie J. Kaplan Ph.D., re: studies titled
Nutraceutical Treatment of Mental Disorders in Adults: An RCT with Bipolar DisorderandFibromyalgia Clinical Study.(2001-10-25) 2002-01-04. Available from http://www.circare.org/FOIA/hc_cta_20020104.pdf
Dr. Waddington continued:
With respect to research, I know there was an application under the previous regulations for research. I was involved with those discussions. It was finally left where we said to the researcher 'It looks like you can go ahead; please submit your final report'. And it didn't come in. We can't move forward on research that doesn't proceed.
Source: 37th Parliament, 3rd Session: Standing Committee on Health, Evidence. 2004-04-22. Accessed on 2006-11-29 at: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=80774
The following statement is contradicted by Health Canada's correspondence directing termination of the placebo controlled clinical trial testing EmpowerPlus in subjects with bipolar disorder:
Further to my correspondence of October 11, 2001, regarding ongoing clinical trials with Empower +, this is to inform you that the Clinical Trials Application for Empower + has been reviewed by the Therapeutic Products Directorate and is considered not satisfactory according to Division 5 of the Food and Drug Regulations. Please see attached letter to Dr. Kaplan that outlines the concerns raised by the Therapeutic Products Directorate.
As a result of this decision, the trial must be terminated and all the study subjects must be notified.
Source: Akoury M. Health Canada letter to Ian Mitchell with attached document, Information Request to Bonnie J. Kaplan Ph.D., re: studies titled
Nutraceutical Treatment of Mental Disorders in Adults: An RCT with Bipolar DisorderandFibromyalgia Clinical Study.(2001-10-25) 2002-01-04. Available from http://www.circare.org/FOIA/hc_cta_20020104.pdf
Why do Dr. Waddington's statements conflict with Health Canada's directive to Drs. Kaplan and Mitchell?
What's all this about? MP James Lunney is campaigning to pass his Private Members Bill C-420 to amend the Food and Drugs Act; an excerpt of his speech given on 2004-04-22 is quoted below. Canada recently enacted legislation governing Natural Health Products following extensive national consultation and expert recommendations. MP Lunney, however, objects to even these loose regulations because they too prohibit the distribution of products to treat, ameliorate, or cure disease without offering acceptable evidence of efficacy, directions for safe use, or that they contain what's claimed on the label. His solution is to do away with the category of Natural Health Products altogether and classify these products sold for therapeutic use as foods. C-420 would also strike down Schedule A of the Food and Drugs Act, which lists serious diseases for which therapeutic claims cannot be made without adequate evidence. When confronted by the inevitable problem that foods
cannot carry therapeutic claims, his proposed solution is to amend that too. It seems these are the circumstances that would be necessary, in his view, for Truehope and several similar businesses he favors to promote and sell their products in Canada without fear of regulatory interference. We hope Canadians are wiser than this, and take a lesson from the recent U.S. debacle that finally led to the removal of ephedra from the market.
MP Lunney's support for EmpowerPlus seems to have led him to make the following peculiar assertion:
The last word on that particular product I'd want to say is this. I don't have this in both languages, but they say a picture is worth a thousand words. I have here pictures of research done by Dr. Bryan Kolb at the University of Lethbridge; he is a world-renowned neuroscientist. He doesn't work with humans; he works with rats. The pictures I have here are of rats that have had lobotomies. Now, some people would think that's a nasty thing to do to a rat, but Dr. Kolb would cut out sections of their brains and then see what functions they could and couldn't do. Then he would test various things to see if they'd improve function.
Dr. Kolb put these rats with lobotomies on Empower Plus. Not only did they recover their function, amazingly, their brains actually re-grew. I have pictures here; perhaps members would like to see them. There are only a few of you here, and you'll be glad to look at these pictures. A picture says a thousand words.
Source: 37th Parliament, 3rd Session: Standing Committee on Health, Evidence. 2004-04-22. Accessed on 2006-11-29 at: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=80774
A picture may be worth a thousand words, but accuracy is worth more. According to the University of Lethbridge, the study MP Lunney refers to was not conducted by Dr. Bryan Kolb, but rather by a graduate student named Celeste Halliwell, and we await its publication in the peer-reviewed literature.
On 2005-08-13 The Scientist published this article contradicting MP Lunney's claims about Dr. Kolb's work:
Canadian MP misrepresents data. Marvin Ross. The Scientist. 2005-08-12.
URL: http://www.the-scientist.com/news/20050812/01/printerfriendly
Several days later MP Lunney responded in a letter to the Nanaimo Daily News:
MP Lunney responds to supplement story. James Lunney M.P. Nanaimo Daily News. 2005-08-17.
URL: http://www.canada.com/search/story.html?id=1b34f584-f5ca-4e6c-8a10-880bf571c415
On 2005-05-03 in response to a witness who made unfavorable mention of EmpowerPlus, MP Lunney reiterated the lobotomized-rat claims rejected by Dr. Kolb:
He doesn't know about the studies at the University of Lethbridge with Dr. Bryan Kolb and the amazing regrowth of rat brains when they're given this product. He says he's concerned about mental illness, but he knows nothing about the product.
Source: 38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 36 (p. 23, 1140). 2005-05-03. Accessed on 2006-11-29 at: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=116242
On 2005-03-09 Private Member Bill C-420 was reintroduced.
38th Parliament, 1st Session: Standing Committee on Health, Private Member's Business. 2005-03-09. Accessed on 2006-11-29 at: http://www2.parl.gc.ca/HousePublications/Publication.aspx?pub=hansard&mee=68&parl=38&ses=1&language=E#OOB-1166006
EmpowerPlus and the regulation of natural health products by Health Canada were also raised or debated at the following meetings of the Standing Committee on Health.
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 43. 2005-05-17. Accessed on 2006-11-29.
Text: http://cmte.parl.gc.ca/cmte/committeepublication.aspx?sourceid=116926
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1853171/HESAEV43-E.PDF
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 42. 2005-05-16. Accessed on 2006-11-29.
Text: http://cmte.parl.gc.ca/cmte/committeepublication.aspx?sourceid=117031
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1851460/HESAEV42-E.PDF
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 41. 2005-05-12. Accessed on 2006-11-29.
Text: http://cmte.parl.gc.ca/cmte/committeepublication.aspx?sourceid=116841
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1842751/HESAEV41-E.PDF
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 39. 2005-05-09. Accessed on 2006-11-29.
Text: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=117354
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1831714/HESAEV39-E.PDF
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 38. 2005-05-05. Accessed on 2006-11-29.
Text: http://www.parl.gc.ca/committee/CommitteePublication.aspx?SourceId=116380
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1826458/HESAEV38-E.PDF
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 37. 2005-05-03. Accessed on 2006-11-29.
Text: http://www.parl.gc.ca/committee/CommitteePublication.aspx?SourceId=115563
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1817531/HESAEV37-E.PDF
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 36. 2005-05-03. Accessed on 2006-11-29.
Text: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=116242
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1813453/HESAEV36-E.PDF
38th Parliament, 1st Session: Standing Committee on Health, Evidence / Meeting 35. 2005-05-02. Accessed on 2006-11-29.
Text: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=115224
PDF: http://cmte.parl.gc.ca/Content/HOC/Committee/381/HESA/Evidence/EV1806768/HESAEV35-E.PDF
Readers can get a good sense of MP Lunney's support for EmpowerPlus by reading his official press releases, which are available in EmpowerPlus Section VII following the Media Coverage
section. Available from http://www.circare.org/FOIA/atipindex7.htm
It seems Truehope and Dr. Kaplan's research is of great concern to MP Rob Merrifield. It's difficult to imagine what the source of information is that motivated some of his questions to Diane Gorman of Health Canada during her appearance before the committee on 2004-02-26. Health Canada did not interrupt EmpowerPlus shipments into Canada that complied with the Personal Use Importation Directive, rather only commercial shipments and sales generated in Canada — which Truehope assured Health Canada were not taking place. Mr. Merrifield's assertion that suicides happened is alarming and every effort should be made to confirm whether this is true, and under what circumstances it happened. If correct, it suggests a previously unreported and extremely dangerous adverse discontinuation effect of EmpowerPlus. Suicide following abrupt discontinuation of a drug manifestly requires physician supervision of the use of such a drug.
Mr. Rob Merrifield: There is a major issue that many of us as members of Parliament have been dealing with, with regard to a product that is coming in from the United States. I'm sure some of you have heard about Empower Plus. It's a product that has been used for people who suffer from depression. It has had some remarkable results. The problem is we're not able to get this product in and it is being held up at the border.
I'm really having a difficult time understanding where, as a department, you are coming from on this product. I don't believe there has ever been a case of anyone becoming ill, or having an adverse reaction, or having any kind of concern with the use of this product. Yet a number of individuals are telling me they have a very difficult time getting this product into Canada. I know we had a briefing on it here a year ago, or last fall, saying this wouldn't happen. It is still being held up at the border and individuals are in some serious situations at times.
I wonder if you could give me your take on exactly what's going on there.
Ms. Diane Gorman: I'd be happy to answer that one, Mr. Merrifield. I'm well aware of the product.
I think what we first need to establish is that this particular product makes claims that are of a very serious nature in terms of its ability to treat, for example, bipolar depression, anxiety, or schizophrenia.
The natural health products regulations are not intended to deal with products that have those levels of claim that haven't been subject to clinical trials. One of the discussions we have had with proponents of that product is that if the product is effective in the way they describe it to be, Canadians should have access to that product and it should be subject to the same regulatory scrutiny as other products are, and certainly products that make those serious claims.
We are in discussion with an individual who may wish to sponsor a clinical trial with regard to that product.
You may also know that the department is in litigation with the proponent of this product and that the RCMP has been involved. Therefore, there are elements of this particular case that you'll appreciate I can't speak about freely.
However, when you talk about adverse events, we do have information about those and we do have information about at least one individual — and it's not isolated to this one individual — who behaved in some very serious fashion while on this product.
So our concern is, first of all, that the health and safety of people using this product is important, and if this product does have value in terms of the claims it makes, that it be tested, that it be subject to clinical trials. The fact is, it is coming in from the United States but it is not approved in the United States. It is being imported through mechanisms that are outside Canadian law, and that's the reason the department is involved.
(1205)
Mr. Rob Merrifield: I understand that. If it's commercially sold in Canada — and I think this is what your department has said — it should follow the rules of any other product licensed in Canada. But if it's individual choice, they should be able to import that and use it, for their own use, as just the freedom of being able to do that.
You say there are some individuals who had some adverse reactions and reacted erratically on this, but there are many others I've heard of having the same situation when they were not on it, in the sense of some claims of a number of suicides because they were not on it. I know we're talking about a difficult issue when dealing with this illness.
It is just something that I can't get my head around, because there was a clinical trial going on in Calgary, as you are aware. It was shut down, and some of the data I've seen coming out of even that trial, as far as it went, are pretty significant. But I just don't understand why there is such resistance to this product? The gain outweighs the pain, in my estimation. But maybe I'm not getting the whole picture and maybe you can clue me in on it.
MP Merrifield appears to be confused. If he supposes these alleged clinical trial results are based upon the product Truehope and his various constituents are so keen to import, he is likely wrong. Data he saw [god help us] from the trial at Calgary involved the product Truehope does not currently distribute or promote, and has not distributed or promoted since their separation from Evince International in October 2002. If he is concerned that the product used in the clinical trial be available to Canadian citizens, he is likely acting on behalf of the wrong company. Evince International in Utah distributes the product tested at Calgary under the trademarked name Equilib.
Surely he can discern that Truehope's current product is not the same product as is described in Dr Kaplan's papers. In his defense, however, this would be difficult to do exclusively on the basis of information on the Truehope web sites or reported in popular media articles.
MP Merrifield would likely also confuse research subjects enrolled in Dr. Kaplan's clinical trial which Health Canada shut down: according the consent form for the study titled Nutraceutical Treatment of Mental Disorders in Adults: An RCT with Bipolar Disorder
Dr. Kaplan assured them of confidentiality:
All information that is collected about you in this study will be held in the strictest confidence. The only people who will have access to the information required for this research project are the study investigators and designated staff. The final results will be reported as part of a large group as numbers and percentages. Your name will never appear in any reports related to this study. During this study, it will be necessary for a member of the research team to look at your previous medical records. You are assured that this will also be handled in a confidential manner. (1)
What data did MP Merrifield see from this trial, which he judged to be pretty significant?
If we believe the consent form, MP Merrifield should be either a study investigator or designated staff. Which is it?
Ms. Diane Gorman: Right, and again, I don't want to repeat myself, but if that is true, then that should be known and the product should be available through the legal mechanisms that exist in Canada.
The clinical trial, for your information, was not a trial approved by Health Canada, and certainly Canadians hold us to a standard that they do not want clinical trials undertaken in Canada if they have not been approved and are not monitored by Health Canada.
So there are a series of issues here, all of which should be dealt with within the law, so that the health and safety of Canadians is respected and individuals are not caused harm by this product, either in terms of the health issues or in terms of the financial issues.
Source: 37th Parliament, 3rd Session: Standing Committee on Health, Evidence. 2004-02-26. Accessed on 2006-11-29 at: http://cmte.parl.gc.ca/cmte/CommitteePublication.aspx?SourceId=73115
The testimony, speeches, and questions above fly in the face of recommendations made by the Standing Committee on Health just one month earlier. Reading their recommendations after the excerpts above makes us wonder if the committee is aware of its own report, the applicable section of which is abstracted below.
Just a few weeks earlier, the Standing Committee on Health issued a report titled Opening the Medicine Cabinet: First Report on Health Aspects of Prescription Drugs
which enumerated the committee's concerns about clinical trials and specifically with Health Canada's ability to ensure the safety of research subjects. For some perverse reason, the committee is apparently willing to suspend these basic rights for research subjects recruited into clinical trials testing EmpowerPlus. It's apparently perfectly fine that a child should be hospitalized after using EmpowerPlus or that a young man with schizophrenia should spend a year in jail when his condition deteriorated on EmpowerPlus. This is same country that held national meetings on the use of placebos in clinical trials, yet appears oblivious to the fact that subjects in the EmpowerPlus RCT for bipolar disorder weren't told their current medications would be prohibited, and in fact were inaccurately reassured of just the opposite. (2) The relevant section of the committee's report appears below.
Clinical Trials
What We Heard
In the process of drug development, clinical trial research is essential to provide scientific data on a drug's safety, efficacy and optimal dosage. Clinical trials involve direct observation of human subjects. Health Canada then uses the data to evaluate a company's application for marketing a product for human use.
In Canada, regulatory requirements for clinical trials on drugs were developed in the 1960s. In 2001, changes to the regulations included an emphasis on the importance of research ethics boards and the establishment of a new inspection program. In general, a drug sponsor applies to Health Canada for authorization to conduct a clinical trial. The application must contain documents, including a copy of the protocol and a copy of the statement, to be set out in each informed consent form, about potential risks and anticipated benefits. Prior approval by a research ethics board is not required when making an application. However, prior to the commencement of a trial, the sponsor must identify the research ethics board and obtain research ethic board approval for the clinical trial protocol and for the informed consent form. After the clinical trial is initiated, inspections by Health Canada verify compliance with the regulatory requirements.
…
Witnesses pointed to uneven standards and inconsistent operations among research ethics boards across the country. Currently, research ethics boards are not subject to federal regulations. Witnesses expressed concern about the lack of a standard accreditation system or regular audits for research ethics boards. Presently, the Canadian Institutes of Health Research expects funding recipients to adhere to the Tri-Council Policy Statement on ethical conduct for research involving humans. In addition, the National Council on Ethics in Human Research, a voluntary body made up of representatives from key organizations in clinical research and from the public, assists research ethics boards in interpreting and implementing guidelines for the ethics of research involving human subjects. However, there is no single national body mandated to provide oversight for the ethical conduct of human research in either the public or private sector.
…
The Health Products and Food Branch Inspectorate recently conducted inspections to validate data collected in the conduct of clinical trials as well as to increase the protection of enrolled subjects. A July 2003 report titled Summary Report of the Inspections of Clinical Trials Conducted Under the Voluntary Phase observed a number of deficiencies in areas related to records, to accuracy, to completeness and maintenance of source data, to systems and procedures for processes, and to informed consent forms for subjects enrolled in clinical trials.
Do tell.
What We Think
The Health Committee believes that the health and safety of individuals who participate in clinical trials must be paramount. While it supports the current regulatory framework, it wants further measures to ensure that Canadians are not exposed to any undue risks during clinical drug trials. It calls for more rigorous scrutiny of clinical trial applications and an increase in the number of inspections.
…
The Committee strongly supports the development of accreditation and oversight for research ethics boards responsible for assessing clinical trials. It also wants a full and open public discussion about confidentiality agreements that currently prevent disclosure concerning negative outcomes in clinical trials. In particular, it feels that information on all serious adverse drug reactions observed during clinical trials and reported to Health Canada should be made publicly available.
The Committee therefore recommends that:
Recommendation 1
- Health Canada significantly increase the number of inspections conducted annually for all phases of all current clinical trials for prescription drugs involving human subjects and produce public annual reports of the findings;
- Health Canada introduce measures to ensure public confidence in the clinical trial process, starting with a public database that provides information on trials in progress, trials abandoned and trials completed;
- Health Canada develop standards that establish an accreditation process for research ethics boards assessing clinical trials;
- Health Canada conduct consultations aimed at discouraging or at least minimizing the use of confidentiality agreements when conducting clinical trials.
Source: Opening the Medicine Cabinet: First Report on Health Aspects of Prescription Drugs. Report of the Standing Committee on Health. April, 2004. Accessed on 2006-11-29 at: http://cmte.parl.gc.ca/Content/HOC/committee/373/heal/reports/rp1282198/healrp01/healrp01-e.pdf
Why on earth would the committee recommend increasing human subject protection when they put Health Canada on the carpet for attempting to enforce existing protection of human subjects in clinical trials of EmpowerPlus? Are some research subjects more deserving of protection than others? Which ones get protection and why?
Notes
1. Kaplan BJ. Consent Form. Nutraceutical Treatment of Mental Disorders in Adults: An RCT with Bipolar Disorder. 2001-11-07. Available from http://www.circare.org/FOIA/uc_137_139.pdf
2. Kaplan BJ. Consent Form. Nutraceutical Treatment of Mental Disorders in Adults: An RCT with Bipolar Disorder. 2001-11-07. Available from http://www.circare.org/FOIA/uc_137_139.pdf
It will be your regular physician who continues to monitor (and possibly modify) your medications. Your physician will be informed as to which group you are in, in order to make wise decisions about any potential medication adjustments, but he or she will not be able to disclose that information to you or your family.
Compare this information with: Akoury M. Health Canada letter to Ian Mitchell with attached document, Information Request to Bonnie J. Kaplan Ph.D., re: studies titled Nutraceutical Treatment of Mental Disorders in Adults: An RCT with Bipolar Disorder
and Fibromyalgia Clinical Study.
(2001-10-25) 2002-01-04. Available from http://www.circare.org/FOIA/hc_cta_20020104.pdf
Updated: 2007-04-01
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