Welcome to the May 2023 chapter newsletter. Not too much going on this month, but please check out some new member profiles from Julie and Anna below, as well as some book club notes from Paul. 

For this May’s music, let’s try some cool summer jazz. “Night Dreamer” by Wayne Shorter is a deeply introspective record and one of my favorite jazz albums of all time. It came out in 1964 and, like the best records from that era, has aged like fine wine. Invite your friends over, crack open your favorite craft beer on your back patio, and relax to this as the string lights glisten overhead. 

Let us know what you think, and remember, you can also read this newsletter on the chapter website. You can find previous newsletters on the website as well. 

CHAPTER NEWS 

• Now accepting programming suggestions

• Join our AMWA North Central LinkedIn Community! Link here. 

CHAPTER EVENTS 

• None in May

FEATURES 

• New Member Profile: Julie Merten 

• New Member Profile: Anna Hayes 

• Book Club Notes: The Illusion of Evidence-Based Medicine

CHAPTER NEWS

Now accepting programming suggestions

Have an idea for an event? Guest speaker? Please reach out to Julie Merten at merten.julianna@chimericmed.com with suggestions for programming in North Central AMWA Chapter- she would love to hear from you! 

If you haven’t already, please fill out her programming survey. 

EVENTS

No scheduled events in May

Stay up-to-date on events by reading the newsletter!

FEATURES

Book Club Summary: The Illusion of Evidence-Based Medicine

By Paul Mamula, PhD

Our book club met via Zoom on April 24, 2023, and discussed The Illusion of Evidence-Based Medicine: Exposing the Crisis of Credibility in Clinical Research by Jon Jureidini and Leemon B McHenry. The book reviews clinical trials that were used to justify use of antidepressant drugs for children and adolescents that along the way to approval used altered study results, employed ghostwriters, and actively promoted off-label use. These were later discovered and ultimately resulted in criminal proceedings and fines. 

About the Book 

The book was published in 2020 and reviews 2 clinical trials. Study 329 was conducted by SmithKline Beecham (now known as GlaxoSmithKline [GSK]) for paroxetine (an SSRI antidepressant) and CIT-MD-18 was tested by Forest Laboratories for citalopram and escitalopram. The book is 8 chapters long and walks readers through the studies and their shortcomings. It also includes 12 Appendices of excerpts from interviews, depositions, and letters to the editor. The authors also describe their reevaluation of CIT-MD-18 and efforts to get the reanalysis published. Chapter 8 proposes solutions to the problems in the current clinical trial system. Chapter notes, bibliography, and acknowledgements round out the book.   

The Controversy and Outcomes 

The controversy in The Illusion of Evidence-Based Medicine revolves around altered criteria used for assessing success in one trial and inclusion of unblinded study participants in the other, both of which changed negative results into positive ones. Both companies also coached marketing staff on how to promote off-label use. Exposing the malfeasance took place over the period 2004 to 2012 and was sparked by investigations in the United States and the United Kingdom. The authors weave the clinical trial irregularities and follow-up but their presentation is a little muddled. Jureidini and McHenry published additional assessments of the trials before their book was published in 2020,1-3 and a summary article in BMJ in 2022.4 Ultimately GSK and Forest had to pay for their irregularities. GSK settled for $3 billion, an amount that also included a $1 billion fine for “preparing, publishing and distributing a misleading medical journal article that misreported that a clinical trial of Paxil demonstrated efficacy in the treatment of depression in patients under age 18, when the study failed to demonstrate efficacy.”5 Forest Laboratories paid $313 million to resolve criminal and civil liabilities for misuse of their drugs6 and another $164 million for criminal violations.7 

Complaints and Solutions  

The authors make a good case for complaints about the trials that include the companies: 

• employing ghostwriters and token authors for papers written,  

• changing trial protocols and altering trial results,  

• engaging in publication planning with ghostwritten articles and gratuitous authors, and  

• coaching sales staff to encourage off-label use.  

Since these events occurred in the early 2000s, some of these issues, notably ghostwriting, have been partially addressed; however, many issues remain. The authors proposed solutions, but we wondered how much these would cost and how they could be implemented. Nonetheless, more money from independent sources for trials, better study design, and more effective tracking would be welcome. 

The authors present suggestions for mitigating the problems in Chapter 8, and these are also highlighted elsewhere.7 These include: 

• Freeing regulators from drug company financing, 

• Taxing pharmaceutical companies to facilitate public funding of independent trials, and 

• Anonymized individual patient level trials data posted with study protocols on suitably accessible websites so that third parties, could rigorously evaluate the methodology and trial results. 

Jureidini and McHenry also explain other problems that include discussions about Cochrane Reviews, restrictions on pharmaceutical marketing, and suggestions about government investigations, litigation, and punitive damages. These measures would go a long way to rectifying the current situation. 

Quibbles 

We all liked the book but had a few complaints. Kendra Hyland said, ”The book was an informative and eye-opening insight into how pharmaceutical companies manipulate clinical trials and the results to promote drug sales. While the book needed some editing and was redundant at times, it was worth the read.”  

I also liked the book but also found multiple editing deficiencies that included 2 reversed figures (5.1 and 5.2), out of order tables, and a few missing and erroneous references. Perhaps this reflects the decision to use a small independent publisher. The book had been accepted by mainstream publishers but the authors decided to use an independent publisher to avoid any possible conflict of interest with the pharmaceutical industry and to reduce costs. One wonders if the editing might have been better with a larger publisher. I read an Australian copy obtained via interlibrary loan that employed an odd typeface that was glaring and hard on the eyes. 

We found the book a little hard to follow, particularly because the appendices refer to different trials, include letters to editors, and transcripts from different cases. The authors might have incorporated those in the text for smoother reading. I found it distracting to have to flip back and forth. Readers also felt that the authors generalized broadly. Laura Chapin said, ”At times I felt the authors painted every single person as guilty ‘baddies’ operating maliciously, though I question the reality of so many people taking part intentionally and knowingly. It marked a specific time in history that’s interesting to compare to current writing and publishing practices as I’m familiar with. I found it to be thought provoking read overall. Although I don’t work in the pharmaceutical industry, it encouraged me to view my work in medical devices with a different lens.” 

Next Up 

Our next book club will meet on September 25, 2023, to discuss Man’s 4th Best Hospital by Samuel Shem. It is a novel that revisits the characters from Shem’ House of God (Book Club selection for April 26, 2010) and Mount Misery (book club selection for April 30, 2012). Man’s 4th Best Hospital follows the physicians as new corporate owners seek to improve the hospital’s ranking. The characters were based on actual people and provide an interesting look at how medicine has evolved since that original novel. Readers can get also get an overview of the novel and the controversy surrounding it in a recent discussion in JAMA.8 Join us for the discussion (even if you haven’t read the book!). 

References 

1. Le Noury J, Nardo JM, Healy D, Jureidini J, Raven M, Tufanaru C, Abi-Jaoude E. Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ 2015;351: h4320 Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence – PMC

2. Le Noury J, Nardo JM, Healy D, Jureidini J, Raven M, Tufanaru C, Abi-Jaoude E. Study 329 continuation phase: Safety and efficacy of paroxetine and imipramine in extended treatment of adolescent major depression. Inf J Risk Saf Med 2016;28(3):143-161 Study 329 continuation phase: Safety and efficacy of paroxetine and imipramine in extended treatment of adolescent major depression – PMC

3. Jureidini JN, Amsterdam JD, McHenry LB. The citalopram CIT-MD-18 pediatric depression trial: deconstruction of medical ghostwriting, data mischaracteriszation and academic malfeasance. Int J of Risk Saf Med 2016;28(1):33-43 The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance – IOS Press

4. Jureidini J, McHenry LB. The illusion of evidence based medicine. BMJ 2022;376:o702. doi: 10.1136/bmj.o702

5. Thomas K, Schmidt MS. Glaxo agrees to pay $3 billion in fraud settlement. The New York Times, July 2, 2012 GlaxoSmithKline Agrees to Pay $3 Billion in Fraud Settlement – The New York Times

6. Office of Public Affairs. Department of Justice. Drug Maker Forest Pleads Guilty; to Pay More than $313 Million to Resolve Criminal Charges and False Claims Act Allegations. September 15, 2010. Drug Maker Forest Pleads Guilty; To Pay More Than $313 Million to Resolve Criminal Charges and False Claims Act Allegations | OPA | Department of Justice

7. Office of Public Affairs. Department of Justice. Forest Pharmaceuticals Sentenced to Pay $164 Million for Criminal Violations. March 2, 2011. Forest Pharmaceuticals Sentenced to Pay $164 Million for Criminal Violations | OPA | Department of Justice

8. The House of God at 40: The Characters Speak. Published online July 10. 2019 video 51 min JAMA 2019;322(6):486-487 doi:10.1001/jama.2019.9499 The House of God at 40: The Characters Speak | Humanities | JN Learning | AMA Ed Hub