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[Ben Hollinbeck]

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Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

To determine whether the improvement over available therapy is substantial is a matter of judgment and depends on both the magnitude of the treatment effect, which could include duration of the effect, and the importance of the observed clinical outcome. In general, the preliminary clinical evidence should show a clear advantage over available therapy.

For purposes of Breakthrough Therapy designation, clinically significant endpoint generally refers to an endpoint that measures an effect on irreversible morbidity or mortality (IMM) or on symptoms that represent serious consequences of the disease. A clinically significant endpoint can also refer to findings that suggest an effect on IMM or serious symptoms, including:

Breakthrough Therapy designation is requested by the drug company. If a sponsor has not requested breakthrough therapy designation, FDA may suggest that the sponsor consider submitting a request if: (1) after reviewing submitted data and information (including preliminary clinical evidence), the Agency thinks the drug development program may meet the criteria for Breakthrough Therapy designation and (2) the remaining drug development program can benefit from the designation.

Ideally, a Breakthrough Therapy designation request should be received by FDA no later than the end-of-phase-2 meetings if any of the features of the designation are to be obtained. Because the primary intent of Breakthrough Therapy designation is to develop evidence needed to support approval as efficiently as possible, FDA does not anticipate that Breakthrough Therapy designation requests will be made after the submission of an original BLA or NDA or a supplement. FDA will respond to Breakthrough Therapy designation requests within sixty days of receipt of the request.

The findings in this report are subject to at least two limitations. First, the number of reported COVID-19 vaccine breakthrough cases is likely a substantial undercount of all SARS-CoV-2 infections among fully vaccinated persons. The national surveillance system relies on passive and voluntary reporting, and data might not be complete or representative. Many persons with vaccine breakthrough infections, especially those who are asymptomatic or who experience mild illness, might not seek testing. Second, SARS-CoV-2 sequence data are available for only a small proportion of the reported cases.

Beginning May 1, 2021, CDC transitioned from monitoring all reported COVID-19 vaccine breakthrough infections to investigating only those among patients who are hospitalized or die, thereby focusing on the cases of highest clinical and public health significance. CDC will continue to lead studies in multiple U.S. sites to evaluate vaccine effectiveness and collect information on all COVID-19 vaccine breakthrough infections regardless of clinical status. Additional information and resources to help public health departments and laboratories investigate and report COVID-19 vaccine breakthrough cases are available at -19/health-departments/breakthrough-cases.html.

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Rapid advancements in battery technology are poised to accelerate the pace of the global energy transition and play a major role in addressing the climate crisis. With more than $1.4 billion invested in battery technologies in the first half of 2019 alone, massive investments in battery manufacturing and steady advances in technology have set in motion a seismic shift in how we will organize energy systems as early as 2030.

The report illustrates how diversifying applications will create opportunities for new battery chemistries to compete with Li-ion, including: solid state batteries, such as rechargeable zinc alkaline, Li-metal, and Li-sulfur that will help electrify heavier mobility applications; low-cost and long-duration batteries, such as zinc-based, flow, and high-temperature technologies that will be well suited to provide grid balancing in a high-renewable and EV future; and high-power batteries, which are well positioned to enable high penetration and fast charging of EVs.

As the battery market continues to grow, battery technology will contribute to the replacement of natural gas plants and gain a foothold in other new market segments, including heavy trucking and short-range aviation. With this transition, legacy infrastructure across the fossil fuel value chain risks becoming stranded, including gas pipelines and internal combustion engine manufacturing plants. Already, battery cost declines are contributing to cancellations of planned natural gas power generation.

It is clear that breakthrough battery technologies will play a central role in our energy system sooner than previously thought possible, creating diverse opportunities for value creation and capture in the transition to a clean energy economy. But capturing the vast potential requires a holistic approach from public and private sectors alike. Collaborative, systems-based strategies to developing battery-enabled markets will provide an opportunity to hasten the rapid and economic transition to resilient, clean, and affordable energy systems.

The Institute for Healthcare Improvement developed the Breakthrough Series to help health care organizations make "breakthrough" improvements in quality while reducing costs. The driving vision behind the Breakthrough Series is this: sound science exists on the basis of which the costs and outcomes of current health care practices can be greatly improved, but much of this science lies fallow and unused in daily work. There is a gap between what we know and what we do.

The Breakthrough Series is designed to help organizations close that gap by creating a structure in which interested organizations can easily learn from each other and from recognized experts in topic areas where they want to make improvements. The Collaborative methodology has proven methods to spread outstanding improvements across a system. Initially developed with a focus on improvements in health care, the Breakthrough Series model and its "All Teach, All Learn" philosophy is also applicable in non-health care settings.

A Breakthrough Series Collaborative is a short-term (6- to 15-month) learning system that brings together a large number of teams from hospitals or clinics to seek improvement in a focused topic area. Since 1995, IHI has sponsored over 50 such Collaborative projects on several dozen topics involving over 2,000 teams from 1,000 health care organizations. Collaboratives range in size from 12 to 160 organizational teams. Each team typically sends three of its members to attend Learning Sessions (three face-to-face meetings over the course of the Collaborative), with additional members working on improvements in the local organization.

Teams in such Collaboratives have achieved dramatic results, including reducing waiting times by 50 percent, reducing worker absenteeism by 25 percent, reducing ICU costs by 25 percent, and reducing hospitalizations for patients with congestive heart failure by 50 percent. In addition, IHI has trained thousands of people in the Breakthrough Series methodology, thus spawning hundreds of Collaborative initiatives throughout the health care world, sponsored by organizations other than IHI.

Kelly Rowland and Sara Bareilles get to know five artists competing for $100,000 and a shot at a career breakthrough. Blaze, Johnna, Melanie, Mitch, and Sasha introduce themselves with a cover song that best represents who they are - as individuals, and as artists.

Not only was I sick, but I'd brought the virus home and exposed my 67-year-old father and extended family during my first trip back to the East Coast since the start of the pandemic. It was just the scenario I had tried to avoid for a year and a half. And it definitely was not the summer vacation I had anticipated.

Where did I get it? Who knows. Like so many Americans, I had loosened up with wearing masks and social distancing after getting fully vaccinated. We had flown across the country, seen friends, stayed at a hotel, eaten indoors and, yes, even went to a long-delayed wedding with other vaccinated people.

I ended up in quarantine at my father's house. Two rapid antigen tests (taken a day apart) came back negative, but I could tell I was starting to feel sick. After my second negative test, the nurse leveled with me. "Don't hang your hat on this," she said of the results. Sure enough, a few days later the results of a PCR test for the coronavirus (this one sent to a lab) confirmed what had become obvious by then.

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