When it comes to clinical trials, the conversation surrounding increased globalization of medical progress is multifaceted and complex.
Flora Southey, a reporter for Outsourcing-Pharma.com, recently wrote about how the China Food and Drug Administration recently approved new policies to standardize regulations for trials in China run by international pharmaceutical companies.
The news is exciting because it gets the global community closer to something we want: shorter approval timelines, which means getting safe, well-tested treatments on the market and in the hands of patients faster.
But regulating a global clinical trials industry is tricky, from a safety standpoint as well as an ethical and an economic one.
As Garth Tierney and Dr. Silvia Zieher explain in Pharmaceutical Outsourcing, globalization means, well, outsourcing. Much like the outsourcing of factory-made products, pharmaceutical companies are motivated to outsource clinical trials to places where running them is less expensive due to the relative wealth of the nation and populations that are more willing to take part in clinical trials in those countries.
This strategy is becoming increasingly popular. In an article for goBalto, reporter Craig Morgan notes that the number of clinical trials in developing countries has been growing at a study 8-percent rate for more than two decades. That said, 61 percent of clinical trials are still held in America.
Globalization is also a matter of international communication: What’s learned by scientists in one country can benefit the advancement of medicine in countries worldwide — hence all the enthusiasm for China’s new, somewhat more permissive regulations. Now, every country can benefit from trials run in China.
But those benefits only spread if there is genuine transparency in these trials. If scientists, citizens and lawmakers are instead kept in the dark, few people will benefit from those trials.
So far, globalization has promoted transparency in clinical trials, and that’s a good thing. Here’s how our industry can maintain that course.
Different Countries, Standardized Regulations
Globalization is making clinical trials more transparent by motivating the European Union, the U.S. National Institute of Health, the U.S. Departments of Health and Human Services and China’s FDA to implement some new regulations. These regulations mandate better documentation of adherence to ethical guidelines (like informed consent of patients) and reporting of all trial outcomes, even null or negative ones.
These laws have been enacted and continue to be updated and enforced due to pressure between countries, all of which benefit from accurate information, and from watchdog groups like Wemos, which is a leader in human rights.
Sara Reardon, writing for Nature, reports that the NIH is particularly invested in making sure that disappointing trial results — that is, experiments that show that a treatment doesn’t do what was hoped it would do — are as quickly and widely reported as successful trials.
Historically, this has been a problem.
Ed Miesta, writing for Clinical Leader, explains that without federal mandates, it’s difficult to achieve complete transparency regarding null results because reporting those results doesn’t benefit the academic careers of clinical investigators. Scientists advance in academia by winning grants and presenting at conferences, and conference spots and grants are only given to groups whose work seems potentially promising and beneficial. So, there’s incentive to either hide null results or, far more often, simply abandon trials when it becomes clear the treatment isn’t going to work.
Globalization changes this dynamic.
With collaboration between countries, it becomes more vital to standardize regulations and gather and maintain all the data in order to reduce redundancy and ensure accuracy of results. With increased pressure from federal governments to meet these new standards, the pressures that incentivize unscrupulous behavior from some researchers disappears.
Which Companies Are Succeeding?
Some pharma companies are already ahead of the curve when it comes to transparency, and others are struggling to meet the new international standards.
Stephanie Baum, writing for MedCity News, talks about the Good Pharma Scorecard, which is a third-party ranking system designed by Bioethics International. Bioethics International was created by Jennifer Miller, a bioethicist at NYU, to address growing concerns about opacity of clinical trials held abroad, as well as ethical issues surrounding patient consent in countries where overall population health is low.
The Good Pharma Scorecard ranks companies based on how transparent and ethical their trials were that year, as well as how easy it is for members of the public to access trial data. The results from 2017: Johnson & Johnson / Janssen and Sanofi Genzyme tied for first place with a 100 percent transparency score.
Miller hopes that the scorecard will incentivize companies to meet best practices, as transparent companies will come to be seen as more trustworthy and will earn more funding.
Over at TheScientist, Diana Kwon writes that since the Good Pharma Scorecard was implemented in 2014, most companies’ scores have been improving from year to year.
But not every company is doing well with meeting the new standards.
The EU legally mandated more open reporting of negative or null clinical trial results in 2014, writes Ben Hirschler. The new regulations also require the publication of data on safety and side effects of medications found in clinical trials, a pressing concern for the public after the medication Vioxx was found to be unsafe after it had already gone to market.
Unfortunately, AbbVie is now involved in a legal battle related to its drug Humira over compliance to the regulations. They’re trying to redact information the EU wants to mandate as public, and argue in favor of exceptions in certain cases.
Another company struggling to make the mark is Valeant Pharmaceuticals. In The Motley Fool, Alex Dumortier writes that Valeant’s lack of transparency regarding its relationship to specialty pharmacy Philidor RX Services, which accounted for 5.9 percent of Valeant’s revenue in 2015, led to a breakdown of trust in the company and a subsequent loss in the value of the stock.
It’s this same lack of transparency that led to a damagingly low Good Pharma ranking in 2017: Valeant earned just a 50 percent transparency score on that scorecard.
Who Holds Clinical Trial Directors Accountable on a Global Stage?
There are five key groups dedicated to holding clinical trial directors accountable:
1. The United States National Institute of Health
The National Institute of Health both funds a majority of clinical trials with human subjects worldwide and also sets regulations. In his blog, Dr. Michael Lauer, the Deputy Director of Extramural Research, explains how the NIH is working to hold clinical trial directors accountable, as well as how granting works.
2. The European Medicine Agency
The European Medicine Agency is the group responsible for setting up the portals that clinical trial directors in Europe can use to upload their trial results to an EU database. The EMA is also responsible for supervising and assessing this information. They emphasize wanting to avoid unnecessarily duplicating trials due to data going unreported. EMA Scientific Administrator Laura Pioppo explains how newly implemented EMA regulations are moving Europe toward these goals.
3. Wemos and Other Human Rights Groups
Wemos in the Netherlands is a non-profit human rights group working to make sure that vulnerable people, who are more likely to participate in clinical trials in developing nations, are retaining their rights to consent and medical treatment. As an advocacy group, they promote increased transparency not only of the results of trials, but of the conditions of patients within those trials. By recording patient testimony, they’re able to present firsthand information about conditions to governments and regulating bodies to hold directors accountable.
An HPV-drug trial in India was halted when an advocacy group discovered that the girls in the trial did not give informed consent. Following the news, Shah Alam Khan reports the Indian government will develop and implement tighter regulations regarding transparency, both to trial subjects and the public, similar to those created by the NIH and the EMA.
4. Quintiles and Other For-Profit Pharmaceutical Services Companies
Quintiles’ Infosario One app allows “key stakeholders in the drug development process [to] conveniently access site start-up, recruitment and compliance information as well as status updates on data queries and project milestones,” Christiane Truelove writes at PharmaLive. Since the app is more useful the more data it has, Quintiles incentivizes directors to upload information frequently by rewarding collaboration among groups through the app’s design.
Though the company is only able to reward compliance and make it easier, rather than punish non-compliance, it’s still a factor in motivating directors to stay accountable.
STAT was founded by John Henry, publisher of The Boston Globe, as a publication dedicated to in-depth health reporting from all angles: local news, government policies, scientific and technological breakthroughs, and pharmaceutical company ambitions. Their investment in transparency has provoked real change in the past four years.
Recently, STAT launched an investigation and revealed that many research facilities in the United States are failing to report findings to the NIH or reporting them over two years late, in violation of the regulations. According to STAT writer Charles Piller, many hospitals, including New York City hospital, filed reports only after learning the investigation was underway. The NIH director is committed to following up more assertively, and perhaps punitively, with facilities that are late with their reports or have lost the information, thanks to STAT revealing the breadth of the problem.
Will the Future Being Greater Transparency?
As globalized trials expand, there’s reason to be optimistic that there will be more transparency rather than less. Joe Archer, the Associate Director of Trial Disclosure Services at MMS Holdings Inc, tells Ed Miesta that the prevalence of technology designed to makes reporting easier will push facilities and directors to report data on time and in compliance with regulations.
Melissa Fassbender reports in Outsourcing-Pharma.com that the FDA launched a new pilot program in January 2018 to improve the transparency of clinical trials in general, and make trial information about nine drugs approved this year easily available to the public. The pilot program, called TrialScope, will seek public feedback about how easy or difficult the information is to use.
If TrialScope is successful, it bodes well for the future. But, even if the feedback is mostly critical, the FDA can still learn from the program and continue to move toward these goals.
Moe Alsumidae at Applied Clinical Trials says patient centricity is moving to the forefront of clinical trials conversation in 2018. Some sponsors are running and expanding initiatives to communicate directly with subjects via specific technology portals. Facilities are also encouraging patients to drive the studies’ designs, as becoming collaborators makes patients more compliant with treatment regimens. Since patients are the most vocal supporters of transparency, patient-centric studies are inevitably more transparent.
Mark Vermette at MedCity News agrees that patient-centric trials are the future. In addition, facilities in all countries are feeling the pressure to adhere not only to the regulations in their country, but to European and American regulations, as well, so their work might be valuable across the board.
However, the technology to do this efficiently needs time to mature. Once that happens, though, Vermette predicts that transparency won’t be a goal but an industry norm.
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