<![CDATA[The Politics of Prescribing - Blog]]>Tue, 13 Feb 2018 08:55:40 -0800Weebly<![CDATA[TrialsTracker : Missing Clinical Trial Data from Canadian Universities and Institutions ]]>Sat, 26 Nov 2016 16:17:36 GMThttp://adrienneshnier.com/blog/trialstracker-missing-clinical-trial-data-from-canadian-universities-and-institutionsPicture
"Nine Canadian universities and institutions rank in the top 100 organizations with the greatest proportion of unregistered trials without results." And "Canadian universities and research hospitals are among the worst offenders."

The withholding of clinical trial data is common practice in the medical scientific community. Trial data and results may be withheld for a number of reasons (see here, here, here, here, here, and here) This practice is not only harmful to patients, but also undermines the prescribing practices of physicians. Furthermore, suppression of results if they seem to be unfavourable to the sponsoring drug company's profits is a disservice to the medical researchers around the globe whose research may benefit from analysis of those hidden results. As a result, physicians and their patients who receive prescriptions for these medications are underinformed. For example, if results on certain side effects are not released, or are re-coded to seem less alarming (see here), then how will doctors know to warn their patients about these side effects? How will patients know that what they are experiencing is a side effect about which they can go and see their doctor?  How will doctors know to identify as side effects the adverse events that their patients are experiencing? The withholding of data undermines not only doctors, but the very people that medications are supposed to help. Couple this suppression with clever, catchy, and far-reaching marketing campaigns that provide drug advertising to both physicians and patients (see here and here), and we begin to see the difficulty in trying to obtain not only unadulterated results, but also potentially unfavourable results from the clinical trials themselves. Although unfavourable to companies, these results would be favourable to patients, physicians, and researchers worldwide. 

Information on unreleased clinical trial data has been made available with a new online tool called "TrialsTracker", which maintains a list of all of the trials that have been registered on leading clinical trial registries throughout the globe, tracking how many of these trials have been updated with results. Take a look! Sneak peak: "Since Jan 2006, all major trial sponsors completed 25,927 eligible trials and haven't published results for 11,714 trials. That means 45.2% of their trials are missing results."

Trials Tracker

We've been deceived: Many clinical trial results are never published
Restoring Study 329: Efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence
De-coding serious adverse events in Study 329: The work of the RIAT team
Part 2: FDA investigation "Finds Trash Bags of Data"
"How do we face the outside world when they begin criticizing us for suppressing data?" FDA finds that Canadian drug companies have hidden, altered, and destroyed data
Novartis under investigation: An arrest, manipulated data, and 10,000 cases of hidden side effects
Another attempt made to require all clinical trial results to be disclosed on ClinicalTrials.gov
Endemic Fraud: Misrepresentation of clinical trial data
Direct-to-Physician Advertising (DTPA)
Direct-to-Consumer Advertising (DTCA)

<![CDATA[Reporting of financial conflicts of interest in Canadian clinical practice guidelines: A case study analysis of guidelines from the Canadian Medical Association Infobase]]>Mon, 22 Aug 2016 18:18:16 GMThttp://adrienneshnier.com/blog/reporting-of-financial-conflicts-of-interest-in-canadian-clinical-practice-guidelines-a-case-study-analysis-of-guidelines-from-the-canadian-medical-association-infobase]]><![CDATA[How many days per year do doctors receive money from drug companies?]]>Thu, 16 Jul 2015 03:13:52 GMThttp://adrienneshnier.com/blog/how-many-days-per-year-do-doctors-receive-money-from-drug-companiesPictureNumber of days in 2014 that Dr. Juichih Hsu received payments from drug and/or medical device companies. 984 individual payments in total over 403 days. Follow link to interactive calendar on ProPublica for specific payment per day information.
How many days per year do you receive money from drug companies? According to a report from ProPublica on new data on payments from drug and medical device companies, many doctors have received money from industry on 100 or more days per year. Some doctors received money from drug and medical device companies on the majority of days in 2014.  This data comes from that which was disclosed and subsequently released via the US Physician Payments Sunshine Act (PPSA), enacted in 2010 as part of the Affordable Care Act (here, here).

We know that companies only spend money when the likelihood of increasing revenues and profits from spending that money outweighs the risk of losing money - that's good business and how companies stay alive.  We also know that pharmaceutical companies spent over $57 billion dollars in the United States on promotion to doctors in 2004 alone. We know that companies wouldn't spend this money if they didn't expect returns; therefore, drug and medical device companies wouldn't spend money on promotion to doctors unless it was expected to be financially worthwhile. 

The ProPublica report found that rheumatologists interacted with drug and medical device companies more than other specialties with interactions on 40 days, on average, between 2013 and 2014. Endocrinologists, electrophysiologists, and interventional cardiologists closely followed rheumatologists' average interaction frequency. While they still interacted with drug and medical device industries, dentists, chiropractors, neonatologists, and pathologists were among the specialties with the fewest interactions with these manufacturers.  Further, doctors who had the most interactions with industry also had high rates of brand-name prescribing in the US Medicare Part D program.

ProPublica determined drug and medical device company spending in 2013 and 2014 - here's the breakdown in descending order of amounts paid to doctors:
  1. Genentech Inc.: general payments, $387.7 million in royalties for Rituxan, Avastin, Herceptin to the City of Hope National Medical Center in California
  2. DePuy Synthes Products LLC: $94.7 million in royalties
  3. Topera Inc.: $93.1 million in acquisition payments to physician founders
  4. AstraZeneca: $90.9 million in general payments
  5. Pfizer: $82.1 million in general payments
  6. Allergan: $70.7 million in general payments
Here is a breakdown of money spent and type of payment:
  • Royalty fees: $803.5 million in general payment
  • Promotional speaking: $632.4 million
  • Consulting: $369.4 million
  • Food and beverage: $224.5 million in 9.4 million individual payments to doctors.

Here are a few case studies that highlight examples of how much industry spent in 2013-2014 on individual doctors: 

Name: Removed at doctor’s request
Specialty: Nephrology
Number of days from 2013-2014 on which he/she received money: 335 out of 518 days
Number of individual payments: 1,711
Number of drug companies that paid her money: 30
Reported amount of money received from drug companies in 2013-2014: $814,030
Paid for: promotional speaking, consulting, honoraria, travel and lodging, food and beverage, education.
Paid for listening to or speaking about: Bydureon, H.P. Acthar, Samsca, Soliris, Uloric, Colcrys, Tradjenta, Bystolic, Contrave, Edarbi, Edarbyclor, Rituxan, Jardiance, Nesina, Oseni, Kazano, Jentadueto, Benicar, Azor, Invokana, Bydureon, Victoza, Welchol, Velphoro, Qsymia, Androgel, Tribenzor, Prolia, Onglyza, Gengraf, Phoslyra, Aciphex, Remicade, Xarelto, Nucynta, Insulin Pump, Humalog, Afinitor, Myrbetriq, Vesicare, Zemplar, Levemir, Farxiga, Lovaza, Amitiza, Krystexxa, Viibryd, Exforge, Xolar, Synthroid, Tanzeum, Trulicity, Renvela, Brintellix, Oxycontin, Butrans, Prevnar 13, Zetia, Vytorin, Liptruzet, Tudorza, Daliresp, Other.
Positions: Removed at doctor’s request
ProPublica link to payment data: click here

Name: Juichih Hsu
Specialty: Family medicine
Number of days from 2013-2014 on which he/she received money: 403 out of 518 days
Number of individual payments: 984
Number of drug companies that paid her money: 44
Reported amount of money received from drug companies in 2014: $8,591
Paid for: food and beverage, education,  consulting, promotional speaking
Paid for listening to or speaking about: Abilify, Aggrenox, Combivent Respimat, Spririva, Alvesco, Aminiza, Amrix, Androgel, Anoro, Breo, Apidra, Lantus, Apitom, Aubagio, Azor, Belviq, Benicar, Brintellix, Brovana, Bydureon, Bystolic, Celebrex, Flector Patch, Lyrica, Viagra, Colcrys, Uloric, Contrave, Crestor, Daliresp, Tudorza, DC Accu Chek Insulin Delivery, Dexilant, Duavee, Premarin + cream, Duexis, Ibuprofen, Dymista, Edarbi, Edaryclor, Eliquis, Chantix, Farxiga, Exelon Patch, Fetzima, Viibryd, Fluzone, Sklice, Adacel, Grastek, Ragwitek, Dulera, Nasonex, Humalog, Humira, Invokana, Januvia, Junumet, Xarelto, Jardiance, Tradjenta, Spiriva, Jentadueto, Kazano, Oseni, Nesina, Lantus, Apodra, Latuda, Levemir, Novolog, Levemir, Victoza, Linzess, Multaq, Myrbetriq, Vesicare, Namenda, Nascobal cyanocobalamin, Neupro, Nuvigil, Onglyza, Orthoses off-the-shelf, Osteoarthritis of the knee, Pradaxa, Prolia, Pristiq, Qnasl, Quillivant, Qvar, Rayos, Relpax, Saphris, Seroquel, Symbicort, Spiriva, Strattera, Axiron, Cialis, T-Slim Insulin Pump, Tens, Tradjenta, Tribenzor, Trokendi, Tudorza, Daliresp, V-Go, Colcrys, Viibryd, Vimpat, Welchol, Vimovo, Xolair, Zorvolex, Zyvox, Other.
ProPublica link to payment data: click here

Name: John Fritz
Specialty: Family medicine
Number of days from 2013-2014 on which he/she received money: 355 out of 518 days
Number of individual payments: 1,381
Number of drug companies that paid her money: 48
Reported amount of money received from drug companies in 2014: $313,858
Paid for: consulting, promotional speaking, honoraria, accredited training, travel and lodging, food and beverage.
Paid for listening to or speaking about: Alina, Amitiza, Amrix, Androgel, Apidra, Atelvia, Auviq, Axiron, Benicar, Breathtek, Brintellix, Brovana, Bydureon, Byetta, Bystolic, Cardiac monitors - insertable, Celebrex, Cialis, Ciprodex, Cloderm, Combivent respimat, Contrave, Creon, Crestor, Daliresp, DC Accu Chek insulin delivery, Diabetes care, Divigel estradiol, Duexis, Dutoprol, Edarbyclor, Epipen, Exelon patch, Esforge, Farxiga, Fentora, Fetzima, Gralise, Zipsor, Cambia, Horizant, Humalog, Innopran, Invokana, Janumet, Januvia, Jardiance, Jentadueto, Kazano, Lantus, Linzess, Lyrica, Migranal, Morgidox, Moxeza, Myrbetriq, Namenda, Naprelan, NeoSynalar cream kit, Nesina, Niaspan, Nuedexta, Onglyza, Oseni, Osphena, Pain Management, Patanase, Perforormist, Pradaxa, Prevnar, Primlev, Prolia, Promiseb, Protopic, Pylera, Qnasl, Qvar, Rayos, Relistor, SDG-IDD-Allergy, Seroquel, Spririva, Strattera, Sucraid, Sumavel Dosepro, Symbicort, Synalar cream kit/test kit, Testim, Tradjenta, Trokendi, Tudorza, Uloric, V-Go, Vascepa, Vesicare, Vigamox, Viibryd, Vimovo, Welchol, Xarelto, Xiaflex, Xifaxan, Zenatane, Zenpep.
ProPublica link to payment data: click here

These findings are particularly important, given that it is widely recognized that drug company money paid to physicians in the forms of gifts, meals and honoraria, and for travel, consulting, speakers' bureaus, and giving educational talks, among others, influences their prescribing choices, drug recommendations in clinical practice guidelines, and published clinical results and reviews, all of which reach broad prescribing audiences. To read more about this influence, feel free to read some literature below.

*This post relies on information provided by the cited ProPublica webpages as of July 15, 2015. If you believe that any of the information cited is inaccurate, please notify Adrienne via the contact form.

A Pharma Payment a Day Keeps Docs' Finances Okay
Promotion of Prescription Drugs to Consumers and Providers, 2001-2010
Advertising of Prescription-Only Medicines tot he Public: Does Evidence of Benefit Counterbalance Harm?
Following the Script: How Drug Reps Make Friends and Influence Doctors
Who pays for the pizza? Redefining the relationships between doctors and drug companies. 1: Entanglement
Doctors’ education: the invisible influence of drug company sponsorship
Physicians and the pharmaceutical industry: Is a gift ever just a gift?
Industry sponsorship and authorship of clinical trials over 20 years
Interactions between physicians and the pharmaceutical industry: What does the literature say? 
All gifts large and small
White Coat, Black Hat: Adventures on the dark side of medicine
Key opinion leaders: Independent experts or drug representatives in disguise?
Conflicts of interest in cardiovascular clinical practice guidelines
Conflicts of interest among authors of medical guidelines: An analysis of guidelines produced by German specialist societies
A Comparison of DSM-IV and DSM-5 Panel Members’ Financial Associations with Industry: A Pernicious Problem Persists
Separating Continuing Medical Education from Pharmaceutical Marketing
Scope and impact of financial conflicts of interest in biomedical research: A systematic review
Industry-sponsored clinical research: A broken system
Those Who Have the Gold Make the Evidence: How the Pharmaceutical Industry Biases the Outcomes of Clinical Trials of Medications
Selective publication of antidepressant trials and its influence on apparent efficacy
Medicine, Money, and Morals: Physicians' Conflicts of Interest
Association of Funding and Conclusions in Randomized Drug Trials: A Reflection of Treatment Effect or Adverse Events?

<![CDATA[John Oliver hits the nail on the head : Marketing to Doctors]]>Tue, 10 Feb 2015 15:54:04 GMThttp://adrienneshnier.com/blog/john-oliver-hits-the-nail-on-the-head-marketing-to-doctors
<![CDATA[New Canadian Legislation : Protecting Canadians from Unsafe Drugs Act (Vanessa's Law)]]>Mon, 10 Nov 2014 01:48:45 GMThttp://adrienneshnier.com/blog/new-canadian-legislation-protecting-canadians-from-unsafe-drugs-act-vanessas-lawPicture
In 2013, Terence Young, Member of Parliament for Oakville, Ontario introduced the Protecting Canadians from Unsafe Drugs Act (Vanessa's Law), which has amended the Food and Drugs Act.  Vanessa's Law received unanimous support from the House of Commons.  It was signed into Canadian law on November 5, 2014.  
Vanessa's Law has received Royal Assent and is now Canadian law.  This Act applies to prescription medications, over-the-counter medications, vaccines, gene therapies, cells, tissues and organs, and medical devices (see Health Canada Q & A, here). 

Alongside Plain-Language Labeling, Vanessa's Law aims to protect Canadians who take both prescription and over-the-counter medications by requiring more comprehensive safety warnings from drug manufacturers, giving Health Canada the power to order unsafe drugs off of the Canadian market when dangers become clear, require mandatory adverse drug reaction reporting, and create a robust warning system for patients. Vanessa's Law gives Health Canada, Canada's federal health products regulatory agency, the ability to collect safety information on products approved to be marketed in Canada and require additional transparency on clinical trial registration, Health Canada's regulatory decisions, and company disclosure of confidential business information.

Vanessa's Law gives Health Canada the power to:
  • Initiate mandatory recalls for unsafe products
  • Impose new, tougher penalties for companies that market unsafe products (including jail times and fines of up to $5 million per day, rather than the previous $5000 per day)
  • Provide Canadian courts with the ability to impose harsher fines if violations were intentional (for example, courts may decide that an appropriate fine is the the total profit earned from the drug or device in question)
  • Order, and take a directing role with, drug companies to revise medication labels, including health warnings for children, to ensure that they are labelled clearly and in plain language to accurately reflect the health risk information
  • Order drug companies to conduct additional testing on a pharmaceutical product, including when new risks or adverse events are identified in certain at-risks populations
  • Enhance surveillance on adverse events by requiring mandatory adverse drug reporting by healthcare institutions
  • Require new transparency measures regarding Health Canada's regulatory decisions about granting drug authorizations (i.e. requiring transparency for both approval and rejection of drugs submitted to Health Canada for market approval)
  • Require information about authorized clinical trials to be posted on a public clinical trial registry
  • Require that "confidential business information" is more clearly defined and that such information about a product is disclosed if it may pose a serious risk to Canadians
  • Seek injunctions to ensure that Health Canada's orders are followed.

A well-deserved congratulations to MP Terence Young and his team for their unwavering persistence, determination, and hard work to achieving passing the Protecting Canadians from Unsafe Drugs Act (Vanessa's Law).

Moving forward, all Canadians depend on, and are looking to, Canadian regulatory officials to smartly, appropriately, and effectively enforce this new legislation and in a timely manner.  All Canadians of all ages, who take or will ever take medications, depend not only on the presence of Vanessa's Law, but also its enforcement.

Legislation: Protecting Canadians from Unsafe Drugs Act  (November 6, 2014)
Health Canada: Protecting Canadians from Unsafe Drugs Act
Protecting Canadians from Unsafe Drugs Act (Vanessa's Law)
Bill C-17: Protecting Canadians from Unsafe Drugs Act (Vanessa's Law)
Overview of Vanessa's Law
Harper Government Announces Passage of Vanessa's Law - Modernized Laws for Drugs and Medical Devices Mark a New Era in Canadian Patient Safety
"How do we face the outside world when they begin criticizing us for suppressing data?" FDA finds that Canadian drug companies have hidden, altered, and destroyed data

<![CDATA["How do we face the outside world when they begin criticizing us for suppressing data?" FDA finds that Canadian drug companies have hidden, altered, and destroyed data]]>Sat, 13 Sep 2014 07:01:46 GMThttp://adrienneshnier.com/blog/how-do-we-face-the-outside-world-when-they-begin-criticizing-us-for-suppressing-data-fda-finds-that-canadian-drug-companies-have-hidden-altered-and-destroyed-dataPicture
It is a commonly known fact that pharmaceutical companies have suppressed unfavourable research.  For example, in 1998, GlaxoSmithKline withheld clinical trial data, which showed that paroxetine (Paxil) was an ineffective treatment for depression in children and adolescents.  Another example features GlaxoSmithKline. In an internal company memo, a GlaxoSmithKline employee stated that "It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine".  Moreover, internal industry memos were released during litigation against AstraZeneca.  These memos revealed that the company withheld data on quetiapine (Seroquel) because its staff were not "...100% comfortable with this data being made publicly available at the present time...however I understand we have little choice...Lisa has done a great 'smoke-and-mirrors; job!"  A 1999 AstraZeneca email begged the question, "The larger issue is how do we face the outside world when they begin criticizing us for suppressing data?" Pfizer, Parke-Davis, Merck, and other pharmaceutical companies have also been found to suppress clinical trial data and evidence of safety concerns in order to maintain favourable commercial profiles of their medications.

It is no surprise that a recent investigation by the Toronto Star found that, since 2008, at least 40 Canadian pharmaceutical companies have not only hidden, altered and destroyed data showing that their pharmaceutical products were tainted and unsafe, but also neglected to report evidence of side-effects experienced by patients when taking their medications.  

The Star obtained records from the US Food and Drug Administration through the U.S. Freedom of Information Act because the US FDA inspects Canadian and international facilities when drugs that are manufactured in these facilities are intended to be distributed in the United States; however, unlike the FDA, which publicly posts investigation dates and results on its website, Health Canada does not transparently enforce drug manufacturing laws.  Therefore, Canadian physicians and the public remain unaware of the problems that are revealed through any Canadian investigation.  The FDA website provides dozens of warning letters to Canadian companies, detailing the atrocious conditions in these drug manufacturing facilities.  In general, Health Canada conducts only a small fraction of the number of investigations that the FDA conducts. 

Canadian generic giant, Apotex, has been cited for not only serious manufacturing violations, but also failing to report undesirable test results, as well as tampering with bacterial growth test records.  Since 2008, the FDA has inspected Apotex at least nineteen times. In sixteen of these 19 investigations the FDA found that Apotex employed "objectionable" practices and had "repeated deficiencies".  In one case, the FDA indicated that Apotex "failed to uphold 'its legal obligation'".  These findings were not challenged by Apotex.  Furthermore, the FDA has requested that Apotex investigate whether its middle and top management employees have been involved in data manipulation.

Taro Pharmaceuticals, Canadian generic manufacturer, was cited for keeping drugs on the market even though company testing showed that batches of the medication deteriorated prior to the expiry date indicated on the product label.  Cangene Corp., another Canadian drug manufacturer failed to report of side-effects to authorities. These side-effects included, but were not limited to, blood clots and fever associated with their products.  Although these findings were a result of US FDA investigation, the report also shows that the same drugs in question would have been prescribed to Canadians as well.  Therefore, Health Canada would have been required to investigate these same drug manufacturers, but information about Health Canada's investigations are not made public.  Canadian pharmaceutical policy expert Alan Cassels stated that "Health Canada is giving the least amount of information that they can...Instead of actually increasing people's confidence in the system, this kind of secrecy is degrading it." Cassels asks, "What's the reason for all the secrecy?"

Furthermore, the US FDA has instituted import bans on drugs made by Apotex (in India) and Ranbaxy, an India-based generic manufacturer, which also distributes pharmaceuticals to North America.  The FDA found that India facilities are supplying Canada with medications that the US FDA knows have been adulterated.  Following FDA inspections in 2008, the US government banned imports from two Ranbaxy facilities in India, which also distribute pharmaceuticals to Canada.  In 2013, Ranbaxy's US subsidiary paid $500 million in criminal fines ($150 million) and settlements ($350 million) for its "false, fictitious, and fraudulent statements" to the FDA regarding its drug data and adulterated medications. 

Terence Young, Member of Parliament for Oakville, Ontario has introduced Bill C-17 (Vanessa's Law), which aims to protect Canadians from unsafe drugs.  Bill C-17 is proposed as an Act to amend the Food and Drugs Act.  Alongside the Plain-Language Labeling, Bill C-17 will protect Canadians who take both prescription and over-the-counter medications by requiring more comprehensive safety warnings from drug manufacturers, giving Health Canada the power to order unsafe drugs off of the Canadian market when dangers become clear, require mandatory adverse drug reaction reporting, and create a robust warning system for patients.  As of September 18, 2014, Bill C-17 has undergone its Second Reading in the Senate and has been referred to the Standing Senate Committee on Social Affairs, Science and Technology.

<![CDATA[Minister of Health calls for steps to improve safe prescribing, but no mention of giving Health Canada the authority to recall, withdraw, or require additional safety testing of drugs]]>Fri, 25 Jul 2014 20:43:28 GMThttp://adrienneshnier.com/blog/minister-of-health-calls-for-steps-to-improve-safe-prescribing-but-no-mention-of-giving-health-canada-the-authority-to-recall-withdraw-or-require-additional-safety-testing-of-drugsPicture
Health Canada has undergone criticism for its lack of transparency and its inability to not only monitor prescription drugs after being approved for the Canadian market, but also recall unsafe medications from the Canadian market.  The October 2013 Throne Speech referred to plans to speed up recalls; however, the role and authority of Health Canada, as compared with pharmaceutical manufacturers, was left in question.  Additionally, Health Canada did not reveal their plans for speeding up recalls.  

These plans are important because Health Canada does not have the authority to withdraw or recall previously approved drugs from the market: Health Canada can communicate with drug companies to encourage them to withdraw or recall unsafe drugs, but drug companies have the final say.  Withdrawals and recalls are decided by companies on a voluntary basis.  Furthermore, Health Canada does not make information during the approval process known to experts or the public.  This has garnered further criticism of Health Canada, especially in light of the 2012 and 2013 studies, both of which found that Health Canada maintains practices that are harmful to patient health and publish misinformation, leaving doctors and patients vulnerable to unsafe prescribing.  

The 2012 study, published in JAMA Internal Medicine, found that Health Canada's regular approval processes (standard review = 300 business days) have resulted in a 1/5 (20%) chance that approved drugs will have a serious safety warning after being approved for the market.  Drugs approved through the priority review system (180 business days) had a 1/3 change of having a serious safety warning after being approved for prescription in Canada. In priority review cases, Health Canada does, in fact, have the authority to compel post-market studies and reassessments of safety and effectiveness, Canada's health regulator doesn't properly use this authority.  The 2013 study, published in PLoS ONE, found that Health Canada's Summary Basis of Decision (SBD) documents were generally filled with inconsistency, ambiguity, and misinformation about the safety and effectiveness of drugs.  In fact, over 97% of the documents did not provide complete information about patient withdrawal rates from clinical trials and over 66% of the documents failed to report significant information about the results of clinical trials.

Also in 2013, The Toronto Star obtained a list of 2012 drug reviews after 5 months of requests to Health Canada for this information.  This obtained list contains 151 secret safety reviews of medications completed by Health Canada in 2012. Even after new commitments to transparency, Health Canada will release only a fraction of its drug reviews, citing costs as a setback in compiling the summaries and making them available to the public.   This is why drugs reviews, which had been completed before 2014, will not be released for expert and public viewing.  Arguments have been made, however, that committing resources to increased transparency will improve safe prescribing by physicians and reduce serious adverse events experienced by patients.   Furthermore, although Health Canada has been collecting data on off-label drugs and their serious and fatal side-effects for 6 years, it removes the off-label details before publishing the data in its side-effects database and keeps this information secret.  The FDA provides this data.  [Off-label uses are those for which doctors prescribe approved medications for unapproved uses.]

In light of these and other calls for transparency, on 2 July 2014, Minister Rona Ambrose said that Health Canada will make information on serious and fatal side-effects from, which it has been keeping secret, public.  A Government of Canada press release from today, 25 July 2014, states that "Health Canada will devote  $3.6 million to support the development of evidence-based practices for the most commonly abused classes of prescription drugs: opioids, stimulants, sedatives, and tranquilizers.  The Call for Proposals is aimed at projects that will improve prescribing practices and the educational needs of healthcare practitioners. It also focuses on projects that will develop new approaches, training and tools to improve these prescribing practices."  However, there is no mention of giving Health Canada the authority it requires to make these changes, improve transparency, and require post-market surveillance of drugs in these classes once they have been approved for the Canadian market.  The Call for Proposals focuses on education, guidelines, and training tools for doctors, but this is only a piece of the puzzle.  Health Canada must have the authority to protect Canadians in cases in which recalling, withdrawing, or post-marketing surveillance studies on drugs are required.  As of yet, Health Canada does not have this authority.

Health Canada drug approval system may be harmful to patients
Health Canada's Summary Basis of Decision (SBD) Documents are Inconsistent and of Little Help to Physicians and Patients
Public Senate report acknowledges Health Canada's lack of transparency
Canadian Government: October 2013 Throne Speech
Health Canada’s inability to recall unsafe drugs widely criticized
New Drugs and Safety: What Happened to New Active Substances Approved in Canada between 1995 and 2010?
Quality and Quantity of Information in Summary Basis of Decision Documents Issued by Health Canada
Give Health Canada power to require post-market monitoring of drug safety: Senate reportStar obtains list of red-flagged drugs
Health Canada must disclose information on off-label drug side effects: Editorial
Health Canada to release side-effect data after Star probe
Dangers of off-label drug use kept secret
Health Canada slammed over drug secrecy
Minister Ambrose Takes Steps to Address Safe Prescribing Practices for Drugs Prone to Abuse

<![CDATA[Our new French poster from Evidence Network!]]>Thu, 10 Jul 2014 15:16:18 GMThttp://adrienneshnier.com/blog/our-new-french-poster-from-evidence-network]]><![CDATA[Novartis under investigation: An arrest, manipulated data, and 10,000 cases of hidden side effects]]>Wed, 11 Jun 2014 19:53:51 GMThttp://adrienneshnier.com/blog/novartis-under-investigation-an-arrest-manipulated-data-and-10000-cases-of-hidden-side-effectsPicture
An ongoing investigation into Novartis' study data has resulted in the retraction of Novartis' studies because of concerns that the involvement of Novartis employees manipulated the results.  

Novartis has also undergone scrutiny for its sales representatives allegedly working directly with researchers and study data for its leukemia drugs, Gleevec (imatinib) and Tasigna (nilotinib).  Hospital officials at the University of Tokyo Hospital revealed that doctors let Novartis employees collect patient data and allowed Novartis access to records for all of the 255 trial participants.   According to the hospital director, Takashi Kadowaki, "Novartis employees were 'virtually managing the study'."  The hospital is investigating four other leukemia research programs after receiving information of Novartis employee involvement. 

A panel of third party investigators, all of whom were attorneys, found for than 20 instances of improper behavior among Novartis' local sales representatives.  Novartis also breached clinical trial protocol when its employees had inappropriate involvement in clinical trial data collection processes.  Upon revealing these misconduct allegations, Novartis employees attempted to cover-up their actions by shredding documents and deleting files.  A member of the panel of investigators stated that

                          "We can't rule our that these activities have been carried out at an organizational 
                           level [...] these things have become an everyday occurrence for them, without any 
                           notion that this was inappropriate."

Most recently, Japanese police arrested ex-Novartis employee, Nobuo Shiraishi, for allegedly discrediting studies by manipulating data, which was intended for use in advertising Novartis' blood pressure medication, Diovan (valsartan).   The Japanese government has filed a criminal complaint against Novartis regarding accusations that its Japanese manufacturer exaggerated its advertising of Diovan.

Prosecutors alleged that Shiraishi violated Japan's pharmaceutical laws, which prohibit providing researchers with false data.  Under Japanese law, false-advertising can result in penalties including imprisonment for up to two years, a fine of 2 million yen (US$19,600), or both.

Japanese reports  state that an internal investigation at Novartis revealed 10,000 cases of side effects, which were never disclosed, from one of its leukemia drugs.  These 10,000 cases of hidden side effects data back to 2002, and include data that should have been reported to the Japanese government.  The investigation into these 10,000 cases of hidden side effects is now taking place in addition to allegations from 2013 on 3,000 side-effect reports collected by Novartis last year.

Japanese authorities arrest ex-Novartis employee in data-manipulation scandal
Japanese officials: Novartis failed to report side effects of leukemia drug
Novartis ousts top Japanese execs amid fresh misconduct allegations
Novartis Japan staffers shredded and deleted to cover trial misconduct, panel finds
Japan files a criminal complaint against Novartis for 'exaggerated' Diovan ads

<![CDATA[Part 2: FDA Investigation "Finds Trash Bags of Data"]]>Thu, 05 Jun 2014 01:25:30 GMThttp://adrienneshnier.com/blog/part-2-fda-investigation-finds-trash-bags-of-dataPicture
China and India are two of the largest countries from which Canada and the United States import pharmaceutical products.  The US imports approximately 40% of all over-the-counter and generic drugs produced in India.  According to CNN, the United States imports 40% of its medications from India.  While China resists, India allows the US Food and Drug Administration (FDA) to conduct inspections.   

The FDA has inspected 160 drug plants in India since July 2012, when the US passed the Food and Drug Administration Safety and Innovation Act.  These inspections have revealed that some manufacturing facilities in India have produced medications that were adulterated or contaminated, and manufacturing facilities were often filthy or invested with bugs.  The FDA investigators also caught some of the Executives at these manufacturing facilities lying to them, which has led to felony charges.

On May 7, 2014, the FDA released a warning letter to Sun Pharmaceutical Industries Limited, a pharmaceutical manufacturer in India.  Investigators from the US Food and Drug Administration  (FDA) identified manufacturing violations and deviations from good practices when manufacturing active pharmaceutical ingredients, causing Sun Pharma's affected products to be adulterated under the US Federal Food, Drug, and Cosmetic Act.

FDA inspectors found that Sun Pharma violated FDA regulations by missing fundamental raw data and information necessary to document its analyses.  Two major findings from the FDA investigation were that Sun Pharma had serious data integrity problems and physical records were discarded.

Data Integrity Problems

According to the FDA warning letter, Sun Pharma's analyses failed to provide critical data on:
  • Identification of the samples tested - including name, source, batch number or other distinctive code, and date of sample,
  • Complete record of all raw data generated during each test - including graphs and electronic files from laboratory instrumentation,
  • Test methods used,
  • Sample preparation as prescribed by methods, preparation and testing of solutions,
  • Records of all calculations performed in connection with the test,
  • Test results,
  • The signature of the person who performed each test,
  • Date(s) when the tests were performed, and
  • Date and signature of a second person showing that original records had been reviewed for accuracy, completeness, and compliance with required criteria.

Unlabeled and unidentifiable raw materials were found by FDA investigators in three partially filled bags in Sun Pharma's raw material warehouse and its employees were unable to determine the identity or status of the materials.  Numerous unidentified partially filled bags were also observed by FDA investigators.

Furthermore, Sun Pharma was found to have unacceptable and flawed data handling practices, including using, what employees appeared to call data from "unofficial" injections as "official".  Additionally, Sun Pharma was found by FDA investigators to frequently perform "unofficial testing" of samples, disregarding results, and reporting results from additional tests.  For example, Sun Pharma employees tested a batch sample six times and subsequently deleted the data. In addition to the finding that actual testing results differed from reported results,  the finding that Sun Pharma deleted testing results was common the FDA's report.  Sun Pharma's general lack of reliability and accuracy of generated data is further supported by 47 instances of apparent trial injections of samples which tested out-of-specification and some of these batches were distributed to the US market.  

Discarding Physical Data Records

The FDA's investigation of Sun Pharma revealed that there were many examples of deleted electronic raw data files on computers which controlled testing instruments.  Some deleted files were replaced with identically named files that were used as "official" data files.  Sun Pharma also failed to consistently archive data to its central server.  Other files were deleted with no audit trail or other adequate form of traceability to document deletion activity in the operating system.  These actions allow the data to be manipulated, while appearing to be in sequence, regardless of whether the files were created sequentially.

The FDA investigators also found approximately 10 trash bags containing torn or partially destroyed raw data and manufacturing product records.  The waste bags included the following documents:
  • Calibration check records,
  • Six corrective action and preventive action records, without official documentation that the corrective action described in the torn documents was necessary,
  • Five torn completed preventive maintenance forms, which an employee said that he had mistakenly torn them and, therefore, destroyed the forms,
The destruction of these documents raises serious concerns about integrity of all records generated by Sun Pharma.  
Sun Pharma failed to detect and correct the manipulation, alteration, and premature destruction of records.

Here is a list of pharmaceutical products that Sun Pharma manufactures: http://www.sunpharma.com/indiaproducts

Other cases of hidden and discarded data

This is not the only case in which pharmaceutical companies have discarded or hidden data.  Discarding or hiding data to control and manipulate the evidence base, on which prescribers base their prescribing choices, occurs internationally.  The following are other examples in which pharmaceutical companies have hidden or destroyed data to manipulate the evidence base.  This is not a complete list of drug companies that have hidden data.
  • Takeda (Japan) and Eli Lilly (US partner): US$9 billion in punitive damages for concealing cancer risks associated with its Actos diabetes drug,
  • GlaxoSmithKline (United States): US$3 billion total, $1 billion criminal for off-label promotion and hiding/failure to disclose safety data, $2 billion civil for making false and misleading statements re: safety of Avandia, misbranding of Wellbutrin and Paxil,
  • Roche (United States): refused to release 8 of the 10 clinical trial results conducted on Tamiflu.

*This is Part 2 of a 2-part post. See Part 1: India manufacturer, Ranbaxy, pleads guilty, pays $500 million

FDA Warning Letter to Sun Pharma
FDA Warning Letter to Sun Pharma Finds Trash Bags of Data and Secret Studies
Drug Companies Are Hiding Research
GlaxoSmithKline pleads guilty in $3B US drug fraud case
US Jury Orders Takeda To Pay $6 Billion Over Actos Claims
Higher penalties for big pharma: Data destruction alleged