You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Canada's Decision To Make Public More Clinical Trial Data Puts Pressure On FDA

Enlarge this image toggle caption Teerapat Seedafong/EyeEm/Getty Images Teerapat Seedafong/EyeEm/Getty Images

Last March, Canada's department of health changed the way it handles the huge amount of data that companies submit when seeking approval for a new drug, biological treatment, or medical device — or a new use for an existing one. For the first time, Health Canada is making large chunks of this information publicly available after it approves or rejects applications.

Within 120 days of a decision, Health Canada will post clinical study reports on a new government online portal, starting with drugs that contain novel active ingredients and adding devices and other drugs over a four-year phase-in period. These company-generated documents, often running more than 1,000 pages, summarize the methods, goals, and results of clinical trials, which test the safety and efficacy of promising medical interventions. The reports play an important role in helping regulators make their decisions, along with other information, such as raw data about individual patients in clinical trials.

So far, Health Canada has posted reports for four newly approved drugs — one to treat plaque psoriasis in adults, two to treat two different types of skin cancer, and the fourth for advanced hormone-related breast cancer — and is preparing to release reports for another 13 drugs and three medical devices approved or rejected since March.

Canada's move follows a similar policy enacted four years ago by the European Medicines Agency of the European Union. The U.S. Food and Drug Administration, on the other hand, continues to treat this information as confidential to companies and rarely makes it public.

The argument for more transparency

Transparency advocates say clinical study reports need to be made public in order to understand how regulators make decisions and to independently assess the safety and efficacy of a drug or device. They also say the reports provide medical societies with more thorough data to establish guidelines for a treatment's use, and to determine whether articles about clinical trials published in medical journals — a key source of information for clinicians and medical societies — are accurate.

"Sometimes regulators miss things that have been hidden in those clinical study reports," says Matthew Herder, director of the Health Law Institute at Dalhousie University in Nova Scotia. "Regulators often face resource constraints, they have deadlines, other priorities."

Last year, for example, Canadian researchers used a clinical study report and other previously non-public information from a clinical trial to call into question the efficacy of Diclectin (known as Diclegis in the United States), a commonly prescribed drug to treat nausea and vomiting in pregnancy. The team had requested the information from Health Canada under an older policy, which required researchers to sign a confidentiality agreement and keep the underlying data secret when they published their results. (It "had a chilling effect," Herder says of the now-discontinued policy, and not many researchers made requests.)

Duchesnay, the Quebec-based manufacturer of Diclectin, defended the drug, and the Canadian and American professional societies of obstetricians and gynecologists continue to recommend it. Yet the new analysis gave pause to the College of Family Physicians of Canada, which had previously published two articles recommending Diclectin's use in its medical journal, Canadian Family Physician. The organization took the unusual step in January of publishing a correction, which criticized the independence and accuracy of the two earlier articles. And, citing the new research, it advised physicians to use caution when interpreting recommendations for the drug's use.

Herder and other lawyers and independent researchers who want to see greater transparency in medical research are urging the FDA to follow the example of Canada and the E.U., but without success thus far. To date, the European program, which has been in effect since 2016, has posted clinical study reports for 132 medicinal products whose applications were submitted after January 2015.

Canadian and European regulators lead the way

It is important to have multiple regulators making the data public, says Peter Doshi, an associate editor at the BMJ, an international medical journal, and an associate professor of pharmaceutical health services research at the University of Maryland School of Pharmacy. As it stands now, "If FDA approves first, which often it does, we won't know anything until Health Canada or the EMA makes a decision," says Doshi. "And not every drug, device, biologic out there is going to be approved by these other regulators or even submitted to these other markets."

In addition, redundancy lessens the impact if one regulator changes policy. The EMA, for example, earlier this year moved its operations from London to Amsterdam because of Britain's anticipated exit from the European Union. Clinical data publication "was one of the activities suspended until we are more settled in Amsterdam," says Anne-Sophie Henry-Eude, head of documents access and clinical data publication. No date has yet been announced for its resumption.

Sandy Walsh, a spokesperson for the FDA, says the agency does not have the same freedom as Canadian and European regulators to release clinical study reports. "U.S. laws on disclosure of trade secret, confidential commercial information, and personal privacy information differ from those governing EMA and Health Canada's disclosure of clinical study reports," she wrote in an email.

Some legal experts argue the FDA has more flexibility than it acknowledges. Federal agencies are "entitled to substantial deference" in determining "what constitutes confidential commercial information," Amy Kapczynski, a Yale law professor and a co-director of the university's Collaboration for Research Integrity and Transparency, in The Journal of Law, Medicine & Ethics.

Why drugmakers balk

In response to an interview request sent to the Pharmaceutical Research and Manufacturers of America, Megan Van Etten, the trade group's senior director for public affairs, emailed a statement expressing concern from the industry that Health Canada's new regulations "could discourage investment in biomedical research by revealing confidential commercial information."

Joseph Ross, an associate professor of medicine and public health at Yale University and a co-director, along with Kapczynski and others, of CRIT, maintains that clinical study reports contain little information that companies need to keep secret, and that any such information could be redacted before release. A 2015 report by the Institute of Medicine, now known as the National Academy of Medicine, also called for the FDA to release redacted clinical study reports.

That is the strategy of Health Canada, which discusses possible redactions with the manufacturer. "Health Canada retains the final decision on what information is redacted and published," Geoffroy Legault-Thivierge, a spokesperson, wrote in an email.

So does the EMA, which goes through a similar negotiating process with manufacturers. "We often are in disagreement but at least there is a dialogue," says Henry-Eude. The EMA might agree to redact manufacturing details, for example.

Journal reports often underplay harms, emphasize benefits

Researchers who independently re-evaluate drugs say the reports are critical because the data they need is not readily available in medical journal articles. One analysis showed that only about half of clinical trials examined were written up in journals in a timely fashion and a third went unpublished. And when articles are published, they contain much less data than the reports, says Tom Jefferson, an epidemiologist based in Rome who works with Cochrane, an international collaboration of researchers who conduct and publish reviews of the scientific evidence for medical treatments.

In addition, "journal articles emphasize benefits and underplay or, in some cases, even ignore harms" that can be found in the clinical study report data, says Jefferson. An analysis by experts at the Institute for Quality and Efficiency in Health Care in Cologne, Germany, found "considerable" bias in how patient outcomes were reported in journal articles and other publicly available sources. Public access to clinical study reports can shine a light on such discrepancies.

The FDA has flirted in the past with releasing clinical study reports to the public. In January 2018, it launched a pilot program to post portions of reports for up to nine recently approved drugs if the drug companies would agree.

"We're committed to enhancing transparency about the work we do at the FDA," commissioner Scott Gottlieb, who resigned in March, said at the time.

But only Janssen Biotech, a subsidiary of Johnson & Johnson, volunteered, and its prostate cancer drug Erleada is the lone entry. In June, the FDA announced it is considering shifting its focus from the pilot program to another designed to better communicate the analyses of FDA experts who review drug applications, which the agency has been making public for approved medicinal products since 2012.

But these analyses by FDA reviewers are no substitute for the actual clinical study reports, says Doshi. The reviews reflect "an FDA scientist's take on the sponsor's application," he said. "Without the clinical study report, somebody like me is largely deprived of looking at the underlying data and developing my own take."

Independent researchers like those who took a hard look at Diclectin also want access to clinical study reports connected to regulatory decisions made before the European and Canadian portals were opened.

Since 2010, the EMA has been providing researchers and others with access to clinical study reports for such legacy drugs upon request, while Health Canada is even more transparent, posting requested clinical study reports for drugs and devices approved or rejected before March to its new online portal for anyone to see. So far, 12 information packages are available for older drugs and devices and 11 more requests are being processed.

The FDA has, on occasion, provided reports in response to a Freedom of Information Act request, but researchers seeking this information typically invest "a tremendous amount of time and effort," says Ross. For example, a Yale Law School clinic sued the FDA on behalf of two public health advocacy groups after the agency said it could take years to respond to their FOIA request for clinical trial data for two hepatitis C drugs. In 2017, it won the case and the groups received the data, which they are currently evaluating.

The FDA does not keep track of how many clinical study reports it has released through FOIA, says Walsh. But Doshi and others say such releases are rare, and usually a result of lawsuits or the threat of legal action. In 2011, Doshi requested clinical study reports for Tamiflu, an antiviral medication used to treat the flu. "Eight years later, I think those requests are still alive," he says now. "I don't remember getting a denial. They just sit."

Outside researchers can appeal to companies directly for access to clinical study reports. At least 24 of PhRMA's 35-member companies have signed on to its six-year-old principles for "responsible clinical trial data sharing," committing to the release of synopses of clinical study reports for approved medicines and to considering requests for data and the full reports from "qualified" medical and scientific researchers who submit research proposals.

But researchers are concerned they won't be granted access if companies are not comfortable or sympathetic to their proposals, says Herder. And the companies control the amount of redaction.

The British-based pharmaceutical company GlaxoSmithKline (GSK) has gone further than most in providing public access to its data. In 2013, the company began posting clinical study reports through its own online portal, Clinical Study Register, which is open to the public. "We have published over 2,500 clinical study reports and nearly 6,000 summaries of results — both positive and negative — from our trials on Clinical Study Register," Andrew Freeman, director and head of medical policy, said in an emailed statement. "GSK is leading the industry in transparency."

Even so, GSK controls the level of redaction, says Jefferson of Cochrane, who tried to use clinical study reports posted on the company's portal for a systematic review of HPV vaccines. "Important aspects, for instance the narratives of serious adverse events — those are all blocked out. Big black boxes," he says. "So they are of moderate use."

Meanwhile, many researchers do not realize that Health Canada and the EMA are making clinical study reports available. An online survey of 160 researchers around the world who conduct systematic reviews found that 133 "had never considered accessing regulatory data" and 117 of those 133 "were not aware (or were unsure) of where to access such material." They continue to rely on the limited data in journal articles and other published literature, says Herder of Dalhousie University.

"Transparency is wonderful in theory but unless people actually do the work of getting data and independently analyzing it, transparency is window dressing," he says.

Barbara Mantel is a New York-based reporter who writes about health care and other social issues.

This story was produced by Undark, a nonprofit, editorially independent digital magazine exploring the intersection of science and society.