The Problem: between 1997 and 2001, Bonnie Kaplan, PhD conducted eight clinical trials (one of which was terminated by Health Canada) and obtained REB (Research Ethics Board, the Canadian equivalent of an IRB) approval or funding for an additional five clinical trials to test
EmpowerPlus on adult and pediatric research subjects diagnosed with severe psychiatric disorders, or in the case of two trials, subjects diagnosed with fibromyalgia. In several instances, the conduct of these trials appears to have compromised the rights and welfare of the research subjects. The federal and institutional regulatory safeguards that should have protected the human subjects in these trials seem to be largely ineffective.
Comprehensive document index (under construction 2005-02-06)
Some the more harrowing things to emerge from the documents released under the Access to Information Act
IRB and REB Follies?
- The IRB at the University of Utah, the American trial site, refused to approve these clinical trials because of safety concerns about the investigational drug, and because in their judgment there was likely to be no benefit to the subjects or society. Yet the Utah investigator defied the IRB and conducted the trials all the same.
- In August of 2002, in response to a complaint filed by a CIRCARE board member, the US Office for Human Research Protections issued a determination letter to the University of Utah describing the aforementioned misconduct and added that the informed consents were inadequate.
- In the publication of an open label trial in the Journal of Clinical Psychiatry, principal investigator Bonnie Kaplan asserted that the Conjoint Health Research Ethics Board at University of Calgary approved the trial, yet their REB could not overrule the decision of the Utah IRB, and in fact the University of Calgary had
no information on any research conducted at Utah.
- The Calgary REB is evidently possessed of paranormal abilities. In response to a request for information about these trials, Calgary described REB review,
safety reviews, and approval of clinical trials 5 to 9 months before the initial creation and manufacture of the investigational drug they purported to review.
- This same Calgary REB approved a randomized double-blind placebo controlled trial testing the investigational drug in subjects with bipolar disorder 5 months before the initial creation and manufacture of the drug they allegedly approved. Apparently
equipoise was not a consideration.
- Dr. Kaplan has no training or experience in the diagnosis or treatment of bipolar disorder, schizophrenia, or fibromyalgia, yet she designed and oversaw clinical trials on research subjects with these disorders, and it was to her office telephone that subjects were directed to report their symptomatic changes.
- The informed consent for the randomized clinical trial on subjects with Bipolar Disorder grievously misled research subjects by failing to inform them that they would be removed from their current medications (even if stable). Indeed the informed consent went so far as to describe how the subjects' primary care physicians would manage their medication during the course of the trial.
- Severe adverse reactions between the investigational drug[s] and prescription medications were known to the investigators, yet never disclosed to prospective research subjects.
- Two instances of attempted suicide by patients using the investigational drug were known to the investigators, yet they failed to disclose this to prospective research subjects in the informed consents.
- The informed consent for one pediatric study appears to have misled parents by claiming the investigational drug contained
small amounts of vitamins and minerals, when in fact the study dosage exceeded the Upper Tolerable Intake Limits for Adults, never mind children, for nearly one-third of the vitamin and mineral ingredients.
- Only one of the four informed consents warned subjects not to get pregnant because the investigational drug contained high doses of vitamin A, and so presented a risk of birth defects. Three informed consents were utterly silent about this risk.
- None of the informed consents described the enormous risk of relapsing bipolar disorder following cessation of pharmaceutical treatment, nor did they disclose the fact that the investigational drug might be intolerable or potentially toxic.
- In three of the four informed consents there was no indication that the investigational drug contained vitamins and minerals in dosages exceeding Upper Tolerable Intake Limits. The risks of prolonged intake of mega-doses of vitamins and minerals were not disclosed, nor were the circumstances of manufacture in the US as dietary supplements.
- An employee of the investigational drug's developer incorrectly assured a representative of the Schizophrenia Society of Ontario that the investigational drug was manufactured to
pharmaceutical grade standards, as did the US distributor, for a time, on their web site.
- Prospective research subjects were potentially coerced into enrolling in clinical trials by the over-zealous public pronouncements of Dr. Kaplan, who, for example, made a public pronouncement at a professional conference in London that she had
cured bipolar disorder. This was picked up by Reuters and carried world-wide.
- Confidentiality due research subjects appears to have been violated when, according to CTV reporter Avis Favaro, Dr. Kaplan provided her with the name of a research subject enrolled in her clinical trial. Dr. Kaplan and her research subject were interviewed on national television to announce
startling research results to be presented the next day as a poster at the 2000 annual meeting of the Canadian Psychiatric Association.
- An approved Clinical Trials License from Health Canada was required prior to conducting these studies, yet none was obtained.
- Dr. Kaplan represented to Health Canada through university counsel that she had communicated with four employees at Health Canada from whom she understood that no Clinical Trials License was required. All four Health Canada employees denied this, and one went so far as to say she had no communication with Dr. Kaplan.
- In April 2001 Health Canada intercepted and detained shipments of the investigational drug destined for Dr. Kaplan, yet two double-blind placebo controlled clinical trials continued. One wonders how and what with.
- In the publication of the open label trial in the Journal of Clinical Psychiatry , Dr. Kaplan wrote that she provided directions for the management of subjects' pharmaceutical treatments to their primary care physicians – directions almost certainly prepared by the developer-distributors of the investigational drug product, a retired animal feed salesman and a former dog food distributor, respectively, – neither of whom had any medical training or pharmaceutical expertise.
- In September of 1999, an evidently eminent Canadian who wishes to remain anonymous contacted a high-ranking employee at Health Canada
in an attempt to head off roadblocks and requested a clandestine contact outside the Therapeutic Products Directorate (read
drugs) to whom the investigational drug developers, the aforementioned animal food salesmen, could covertly send their clinical trial data.
- A pediatric open label study conducted in 2000-01 has no entry in the University of Calgary database of approved clinical trials, from which we are left to conclude either that it was not approved by the REB despite assertions to the contrary, or that a major Canadian research institution has at least one serious record-keeping problem.
- The randomized clinical trial on subjects with fibromyalgia, however, did have an entry in the database of approved clinical trials. Alarmingly, at some point during the summer of 2003, this entry vanished from the database, as if it never existed. So in fact it seems that this major Canadian research institution has a second serious record-keeping problem. One wonders what would happen if a subject in this trial became aware he or she had been harmed, or perhaps just simply had some question about their participation in the trial — would the absence of the trial in the approvals database influence the institution's response?
Likely these conditions may strike the reader as implausible, so we'll let the documents speak for themselves.
- OHRP Determination Letter to the University of Utah (2002-08-19) principle investigator Richard Ferre MD and publication: Kaplan BJ, Simpson JS, Ferre RC, Gorman CP, McMullen DM, Crawford SG.,
Effective mood stabilization with a chelated mineral supplement: An open-label trial in bipolar disorder, Journal of Clinical Psychiatry, 62 (12) 2001; 936-944. OHRP objected that clinical research with E M Power+ was conducted despite rejection by the University of Utah IRB, and determined informed consent was inadequate.
Concerns Regarding a Nutritional Cure, CIRCARE InfoMail (2002-06-27)
Index of Documents
Section I, including:
- Documents released under by ATIP by Alberta Science and Research Authority: application for funding, Bonnie Kaplan Ph.D., University of Calgary, Faculty of Pediatrics, 30 November 1998; letters in support of funding application; re-application for funding 30 March 1999
- Investigational Drug Product(s)
- Manufacturers and Distributors
- Current distribution
Section II, including:
- Documents released under ATIP by the University of Calgary
- Investigational New Drug Application for EmpowerPlus®
- Health Canada's rejection of Investigational New Drug Application for EmpowerPlus®
Section III — Clinical Trials, including:
- Approved clinical trials
- Informed Consents
- Funded clinical trials
- Publications and poster presentations
Section IV — ATIP I, including:
- Health Canada Documents I - ATIP file number A-2001-0845/ms
Section V — ATIP II, including:
- Health Canada Documents II - ATIP file number A-2002-00199/ms
Section VI — Canadian Government, including:
- Testimony on EmpowerPlus® Given in Canadian Parliament
Section VII — Related Information, including:
- Criminal Charges Filed Against Distributors of EmpowerPlus®, Judgment, and Trial Transcript (extract)
- Health Canada Advisories and Warnings regarding EmpowerPlus®
- Health Canada Health Hazard Evaluation of EmpowerPlus®
- Media Coverage
- Press Releases
- Letter of Complaint to the Honorable Ann McLellan, Canadian Minister of Health (2002)
Section VIII — Health Canada ATIP A200800462, including:
- Health Canada Health Risk Assessment for Empowerplus® 2007-01-06
- Correspondence RE: Empowerplus® Between Health Canada and Truehope Nutritional Support Ltd., Synergy Group of Canada, Anthony Stephan, and David Hardy
Last Updated: 2012-08-12
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