Latest Drugwonks' Blog
Here we go again. Thomas J. Moore and Curt D. Furberg (in a new JAMA article) accuse the FDA of compromising safety for speed.
As usual, Janet Woodcock places the matter in the appropriate perspective. "I'd like to stress that where there are unmet medical needs, the public has told us they are willing to accept greater risks," Dr. Woodcock said. "The cancer community in particular says we haven't used accelerated approvals enough."
Here’s the truth -- there is no such thing as a "safe" drug. It's the patient who must understand the risks required to achieve the benefit. That’s why the patient voice must be heard during all phases of the regulatory review process.
The Observational Medical Outcomes Partnership (OMOP), a public-private research project aimed at evaluating and validating methods of using observational health care databases for active drug safety surveillance, is considering closer collaboration with FDA’s Mini Sentinel and the Patient-Centered Outcomes Research Institute.
The OMOP executive board proposes working with Mini Sentinel and PCORI in a tentative three-year plan posted recently on the project’s website for public comment.
The OMOP board proposes to “coordinate OMOP’s research with the research and practice of others in the fields of risk and effectiveness identification and interpretation.”
Mini Sentinel is a pilot project for FDA’s Sentinel Initiative, which is envisioned as a national post-market safety surveillance program drawing from a network of medical claims data and electronic health records.
PCORI was established by the Affordable Care Act to sponsor outcomes research, including comparative effectiveness research, for drugs and other medical treatments.
OMOP’s other proposed activities include developing a framework for incorporating observational data and stakeholder perspectives into decision making, as well as methods to enable active surveillance and risk identification for newly marketed medical products.
The problem is that, after this important joint action, we're still hungry for more.
The China State Food and Drug Administration (SFDA) has joined forces with the FDA to shut down 18 Chinese-language web sites selling illegal drugs.
According to China Daily's report on Tuesday, the Sino-U.S. collaboration was launched in June this year and targeted Web sites in the U.S. advertising counterfeit drugs and health food. The 18 sites take down were run and hosted by Chinese speakers and aimed for Chinese consumers including Chinese Americans around the world, said Christopher Hickey, director of the U.S. FDA's China office.
"We welcome and appreciate the role played by the China State Food and Drug Administration to initiate the campaign and hope to continue combined efforts in the global fight against counterfeit drugs," he added.
The Sino-US collaborations was also part of a national clampdown on fake and illegal drugs within mainland China, said SFDA spokesperson Wang Lianglan in the report.
The operation saw police seizing 205 million tablets designed to look like branded drugs for treating male impotence, hypertension, diabetes and cancer, it noted. Wang added the SFDA will step up operations in the rest of the year with other law enforcement agencies and government departments to curb counterfeit medicince.
The next phase will see them enhance inspection of clinical trial for drugs made in China and meant for export to the United States, Hickey said.
For all the talk about a predictable and appropriate FDA pathway for biosimilars, where’s the thinking about what happens after approval?
Since patient safety and product efficacy will be a justifiable cause of angst to wary physicians, how will biosimilars be detailed? And who will do the detailing? Will biosimilar manufacturers need to develop patient assistance programs? What about REMS issues (both IP and implementation)?
Can you say, “authorized biosimilars?”
(And what will Congress and the FTC have to say about that?)
I am an EMR geek who isn’t so thrilled with the direction of EMR. So what, I have been asked, would make EMR something that is really meaningful? What would be the things that would truly help, and not just make more hoops for me to jump through? A lot of this is not in the hands of the gods of meaningful use, but in the realm of the demons of reimbursement, but I will give it a try anyhow.
Read his list here.
The bad news is that solanezumab (Eli Lilly’s experimental Alzheimer's treatment) failed to meet its primary endpoints in two late-stage clinical trials in patients with mild to moderate levels of the disease. The good news is that investigators saw positive signs in some analyses of the studies.
According to Lilly, after combining the results from the total of 2,050 participants in both trials, it found statistically significant signs that the drug slowed memory loss in some patients, many with mild cases.
"We're encouraged by the signals we see here," said David Ricks, president of Lilly Bio-Medicines. He said the solanezumab findings validated the company's heavy investment in Alzheimer's treatments. Lilly plans to discuss the findings with regulators before determining how to proceed with the drug.
Happy talk or hopeful hypothesis? Generally, combining the data from the two trials—aren't considered conclusive but are used to generate hypotheses that require further study and validation.
Importantly, the results from the pooled solanezumab data are to the first from any late-stage Alzheimer’s studies to suggest a benefit from an anti-beta amyloid compound.
Full data from the studies, based on an independent analysis by an academic national research consortium called the Alzheimer's Disease Cooperative Study, will be presented in October at scientific conferences in Boston and Monte Carlo, the company said.
As the Wall Street journal reports, “Much will depend on how regulators interpret the data. Usually the U.S. Food and Drug Administration makes decisions based on how experimental therapies perform in meeting the primary goals of pivotal trials.”
The Journal continues, “In the case of solanezumab, the FDA will have to weigh the potentially limited cognitive benefits against the lack of effective treatments, experts said. The agency could ask Lilly to do additional studies exploring further whether solanezumab does indeed slow down Alzheimer's progression in certain patients.”
True – but an even more important issue is understanding – and rewarding – incremental innovation. “Limited cognitive benefits” is in the eyes of the beholder, but the impact is anything but limited when it comes to our nation’s healthcare wallet.
As the prevalence impact of Alzheimer’s grows, so does the cost to the nation.
One in eight people age 65 and older (13 percent) has Alzheimer’s disease. Nearly half of people age 85 and older (45 percent) have Alzheimer’s disease. Of those with Alzheimer’s disease, an estimated four percent are under age 65, six percent are 65 to 74, 44 percent are 75 to 84, and 46 percent are 85 or older.
If Alzheimer’s Disease was a tradable stock, the demographics of the Baby Boom generation would make it a “must buy.”
The direct and indirect costs of Alzheimer’s and other dementias amount to more than $148 billion annually, which is more than the annual sales of any retailer in the world excluding Wal-Mart.
Is there value in slowing the progression of Alzheimer’s Disease? Certainly.
According to a study in Health Affairs (“Alzheimer's disease care: costs and potential savings”), monthly savings of $2,029 in formal services are possible if disease progression can be slowed. Annual institutional cost savings of $9,132 also are achievable if alternative residential settings are used.
Sometimes the biggest success stories rest on the foundations of failure. The solanezumab trials may have missed their primary endpoints – but they have succeeded in advancing our knowledge of Alzheimer’s Disease and provided a possible new and innovative option for patient’s (and family members) of this draconian disease.
Alas, solanezumab will not be the magic bullet that eradicates Alzheimer’s Disease from our lexicon of suffering – but it may yet be an important addition to our pharmacological armamentarium.
As FDA and then CMS decide on the value of solanezumab, it’s important to remember that innovation is slow. As any medical scientist will tell you, there are few "Eureka!" moments in health research. Progress comes step-by-step, one incremental innovation at a time.
Harvard University health economist (and Obama healthcare advisor) David Cutler has noted: "Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost."
The battle for the heart and soul of 21st century health care is the battle over innovation. And nothing short of victory is acceptable.
To borrow an over-used adjective from the world of global climate change -- we must protect "sustainable" innovation.
The Pink Sheet reports that “An international group of regulators and drug companies have agreed in principle to a framework that sets out eight steps for assessing a drug’s benefits and risks and could set the stage for a global approach to evaluating drugs.”
The framework will not result in uniform decisions across countries, but rather will provide a structure for the benefit-risk assessment process as a number of efforts are underway to make the exercise more methodical and to develop systematic ways for regulators and sponsors to present, communicate and discuss drug data.
Methodologies to reach decisions may vary, but “if everybody follows those same basic eight steps, … any new method that you come up with to develop or to assess benefit-risk should be internationally acceptable because they follow these general eight-step principles,” Lawrence Liberti, executive director of the Centre for Innovation in Regulatory Science, explained in an interview.
The Eight-Step Benefit-Risk Assessment Framework can be found here.
A task force of representatives from eight regulatory agencies and six international pharmaceutical companies, organized by CIRS through its Unified Methodologies for Benefit-Risk Assessment initiative, endorsed the framework following a June 21-22 workshop held in Washington, D.C., to discuss global harmonization of the benefit-risk assessment process. FDA Senior Advisor Murray Lumpkin and GlaxoSmithKline Inc. Senior VP-Global Clinical Safety and Pharmacovigilance Frank Rockhold co-chaired the workshop of regulators, academics and industry representatives.
The CIRS-mediated effort is separate from the International Conference on Harmonization, a long-standing initiative to coordinate regulatory standards between the U.S., Europe and Japan. FDA recently put ICH periodic benefit-risk evaluation standards into draft guidance for post-market safety reporting
While the eight steps coming out of the CIRS effort create structure, the methodology for benefit-risk decision-making will not be uniform soon, if ever. A common lexicon should be developed, according to a synopsis of the meeting, which was not open to the public. But agencies vary in their weighting of benefit-risk parameters and there are regional differences in regulatory and cultural viewpoints, making uniformity difficult.
With general agreement on the framework, stakeholders now can focus their attention on developing those methodologies. “Time should be allowed for pragmatic methodological approaches to be developed, including adequate timing for feedback on best practices to emerge,” the synopsis says.
Four agencies that make up the Consortium on Benefit-Risk Assessment – Swissmedic, Health Canada, Singapore’s Health Sciences Authority and Australia’s Therapeutic Goods Administration – pilot-tested the methodology using information from applications for a drug they previously approved.
The BRAT process was pilot-tested by 13 companies during various stages of drug development. A case study of its application to evaluate Johnson & Johnson/Bayer HealthCare AG’s rivaroxaban found that such methodology can add rigor and transparency to decision-making and is easily used in regulatory settings, such as advisory committee meetings, according to the workshop synopsis.
FDA is field testing its benefit-risk framework with six products. With the FDA approach, reviewers list evidence/uncertainties and conclusions/reasons for five decision factors in a grid format and then analyze the implications. The factors are severity of condition, unmet medical need, clinical benefit, risk and risk management.
(FDA committed to a structured benefit-risk assessment framework for the drug review process as part of PFUFA V.)
Among FDA initiatives in this area is a basic roadmap to be used by patient groups interested in development of patient-reported outcome measures in a specific disease area.
The European Medicines Agency has a benefit-risk assessment methodology that it considers a simple qualitative tool. PrOACT-URL identifies the problem, determines the objective, considers the alternatives and their consequences (presented in tabular form) and makes tradeoffs through swing-weighting of the events. Sensitivity analysis determines the level of uncertainty.
On the developer’s side of the table, Diana Hughes, a vice president in Pfizer Inc.’s primary care business unit, suggested industry form a consortium with the mission of gaining a perspective on unmet medical need and patient experience. Companies should continue collaborating with advocacy groups and develop patient educational programs to elicit information on the most relevant aspects of a disease and advance a common approach to valuing and weighting benefit and risk, she said.
Workshop participants concluded that rules of engagement must be set to avoid any misperceptions of conflict-of-interest during interactions with patients, and that such interactions are consistent, scheduled and balanced. Patients would benefit from education on the inherent nature of uncertainty in benefit-risk decisions, according to the workshop.
If you’re among the 21% of American adults who have tattoos, you might be surprised to learn that there’s no law or regulation that requires tattoo inks to be sterile. The FDA, which has oversight over the inks, treats them like cosmetics and says only that ink manufacturers must use ingredients that have received pre-market approval.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
