Where Is the Scientific Data Hiding?

ByMaryanne Demasi, Ph.D.March 2, 2020

Most of what we understand about the safety and harms of different medicines emerges from published drug trials in the peer-reviewed literature, which is often unduly influenced by industry funding, selective reporting, and a lack of data transparency.

The situation has seriously challenged the trustworthiness of clinical trials published in medical journals, leading some researchers to the “inescapable conclusion … that what we see, even in the most highly regarded peer-reviewed journals, cannot be trusted at face value.”

Ultimately, the buck stops with our drug regulators. They are our last line of defense before medicines enter the marketplace. They exist to assess the evidence base and serve as authoritative arbitrators of the safety and effectiveness of medications.

When a drug company wishes to license a new medicine, it sends drug regulators a dossier of clinical trial data. The dossier includes documents called clinical study reports (CSRs), which contain exhaustive details about the medicine’s performance in drug trials. The regulators then undertake a meticulous examination of the evidence to judge whether the benefits of the drug outweigh its harms.

The stakes are high. Billions of people taking medications rely on drug regulators to keep the public safe. But drug regulators are increasingly under-staffed and lack adequate resources. As a result, public trust in these agencies has waned following scandals such as those surrounding Vioxx and Tamiflu.

One important lesson has been that public access to CSRs can expose major discrepancies between the information submitted to the drug regulator and what the public sees in medical journals. This public access allows independent researchers to correct misinformation about drugs that are widely prescribed in the marketplace.

Statins are an example of a widely prescribed public health drug, taken by millions of people to lower their cholesterol. They have been the subject of a long and bitter dispute among researchers about whether the benefits outweigh the harms in healthy, asymptomatic people (i.e., for primary prevention).

The feud, dubbed the “Statin Wars,” has played out publicly in the media and in the scientific literature, with much of the angst centered on the secrecy of trial data. A group of researchers at Oxford University called the CTT Collaboration closely guards the individual patient data and has denied access to independent researchers.

Remarkably, drug regulators that have licensed statins for primary prevention and presumably hold the evidence to support those licenses have remained silent in the debate.

Why don’t drug regulators just cough up the evidence and settle the debate?

The U.S. Food and Drug Administration (FDA) is sitting on the largest trove of clinical trial data in the world and will not share the data (including CSRs) with the public or independent researchers because it is considered commercially confidential under the Trade Secrets Act (18 U.S.C 1905).  Those who have successfully obtained CSRs usually have taken legal action against the FDA.

In contrast, halfway across the globe, the European Medicines Agency (EMA) began allowing public access to its data archives in 2011. Unfortunately, though, statins were not approved by EMA (only combination formulas).

Instead of finding a central archive at the EMA, we discovered each nation had its own drug regulator. We ended up approaching all 32 countries in the European Union and the European Economic Area to find out which statins they licensed and whether they still held the clinical trial data.

We published our findings in BMJ Evidence-Based Medicine. Three out of 32 countries did not respond despite multiple attempts over several months. Seven countries did not respond in a satisfactory way (due to lack of time, resources, or staff), and 22 responded in full.

Navigating the fragmented system was complex and time consuming, but perhaps the most troubling discovery was that countries that had licensed statins did not actually have clinical trial data in their possession.

For example, atorvastatin (Lipitor) was licensed in 20 countries, but only 12 countries claimed to hold clinical trial evidence relating to its registration. Similarly, rosuvastatin (Crestor) was approved in 22 countries, but only 12 stated they held the trial data.

Are some EU nations licensing statins without examining the evidence? Or if they have examined it, why isn’t the evidence in their archives? And how are independent researchers supposed to access this evidence if it doesn’t exist in the archives? All these questions are part of ongoing research.

Drug regulators are responsible for monitoring the safety of medicines post-approval. Therefore, they should also publicly articulate their position on the statin controversy and make the evidence underlying the choice to license statins in primary prevention available to third parties for independent scrutiny.

Our research has highlighted a major problem. There is no easily accessible archive containing information about the licensing of statins nor a central location for holding the trial data. The transparency of this trial data is vital to making informed decisions about medicines and potentially answering important clinical questions.

If the trial data was made accessible in searchable format with a curated and dedicated web-based resource, it would dispense with the need for protracted freedom of information requests and allow access to what should have always been publicly available.

It is imperative that drug agencies such as the FDA follow the lead of Europe (EMA), and more recently, Canada (Health Canada), and begin the process of publicly releasing crucial scientific evidence about the harms of medications.

As my co-authors have previously stated, “Less bureaucracy and secrecy and more sunlight is needed if regulation is to regain its lost reputation and fulfill its public health mission.”

Additional Reading

Dr. Maryanne Demasi is a well-known investigative journalist whose work on scientific documentaries has been praised by the National Press Club of Australia for exhibiting “excellence in health journalism.”

Demasi earned a Ph.D. in rheumatology from the University of Adelaide in 2004. She currently works as a researcher for the Nordic Cochrane Centre.

Comments on Where Is the Scientific Data Hiding?


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robert meister
March 8th, 2020 at 9:44 am
Commented on: Where Is the Scientific Data Hiding?

Great work Maryanne!

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Emily Kaplan
March 3rd, 2020 at 3:49 am
Commented on: Where Is the Scientific Data Hiding?

This set a dangerous precedent. Why is FDA able to hide behind Trade Secrets for statins but not other drugs? I assume FOIA isn’t helpful here, but what about a wrongful death suit or a malpractice suit? So many people take statins it seems the public’s need to know is paramount.

It occurred to me:

“If a trade secret holder fails to maintain secrecy or if the information is independently discovered, becomes released or otherwise becomes generally known, protection as a trade secret is lost. “ https://www.uspto.gov/ip-policy/trade-secret-policy All you need is a leaker and the trade secret status is gone.

I’ve done some work looking at WTO agreements and thought there might be a way into the data via TRIPS.

Internationally, the rules seem to hold except in cases where the public good overrides the competitive advantage. Given how many people take statins this seems like a reasonable argument. Because the US is member at the WTO they/we are obligated by these standards.

Article 39 of the TRIPS Agreement paragraph three:

This section mandates an obligation to protect data submitted for regulatory review aka drug approval or drug marketing, with a few exceptions:

“Members, when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products which utilize new chemical entities, the submission of undisclosed test or other data, the origination of which involves a considerable effort, shall protect such data against unfair commercial use. In addition, Members shall protect such data against disclosure, except where necessary to protect the public, or unless steps are taken to ensure that the data are protected against unfair commercial use.

While this provision applies to clinical trial data as lex specialis, the obligation should be interpreted in conjunction with 10bis of Paris Convention (“10bis PC”), which states:

(3) The following in particular shall be prohibited:

(i) all acts of such a nature as to create confusion by any means whatever with the establishment, the goods, or the industrial or commercial activities, of a competitor;

(ii) ...

(iii) indications or allegations the use of which in the course of trade is liable to mislead the public as to the nature, the manufacturing process, the characteristics, the suitability for their purpose, or the quantity, of the goods.

You’ve probably already read this, but thought I’d post it here in case you haven’t: https://scholarship.kentlaw.iit.edu/cgi/viewcontent.cgi?article=1149&context=ckjip

Keep up the great work!!! Transparency with this is essential.

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