Improved adaptive trial designs for dose escalation in oncology trials: exploring alternatives to the conventional 3+3 design.

3+3 Design Example

Despite the widespread use of conventional 3+3 designs, new adaptive trial design methods may offer better operating characteristics. For example, the accelerated titration and modified continual reassessment designs allow for smaller cohort sizes and more flexible enrolment decisions.

These designs also provide additional information about pharmacokinetic interpatient variability. However, these methods can lead to accrual of patients to dose levels below the recommended dose for phase II trials.

Dose escalation

Dose escalation is the process by which a clinical trial increases the dose of a drug or vaccine. Typically, three patients are enrolled into a given dose cohort, and if no dose-limiting toxicities are observed, the trial proceeds to enroll additional patients.

Once the MTD is identified, the trial can be stopped when specified stopping criteria are met. These criteria include: a defined number of subjects treated at a certain dose level; the width of the Bayesian credible interval for the MTD at a particular dose level; or the estimated probability that the next patient will not experience DLT at the current dose level.

The 3+3 design is the most popular phase 1 design and is widely used in oncology trials. However, it is not without its problems. It exposes a large number of patients to subtherapeutic doses, and it does not provide a reliable estimate of the MTD (Hansen et al., 2014). Alternatives to the conventional 3+3 design, such as accelerated titration and continuous reassessment, have been proposed.

Dose-limiting toxicities

Many phase I clinical trials use the traditional 3+3 design, but it may not be optimal for every trial. In addition to being a memoryless design, it may not allow for adequate titration of doses that are below the probability of severe toxicity threshold. Other design methods have been developed, such as the accelerated titration designs and the pharmacologically guided dose escalation (PGDE) method. The latter uses a prespecified plasma drug exposure and a patient’s pharmacokinetic data to determine the next dose level.

The PGDE method is computationally simpler than the 3+3 design and can be used to titrate drugs without measuring their blood levels. However, it requires the patient to attend the site and provide pharmacokinetic information in real time, which can be difficult for some patients. This has led to concerns that the PGDE design is not ethically appropriate. However, simulations have shown that it performs well when compared to other model-based designs.


The traditional 3+3 design is the most common dose-finding method used in oncology clinical trials. Its popularity is due to its simple implementation and relative safety. However, there are several drawbacks to this tried-and-true design method. For example, a large proportion of patients are exposed to low (potentially subtherapeutic) doses and few are treated at or near the recommended phase 2 dose. Moreover, the 3+3 design lacks a strong statistical foundation and results in lower precision. Despite these disadvantages, many oncologists continue to use the 3+3 design because it is easy to implement and clinically friendly.

To avoid this problem, researchers can apply a model-based design. These designs are based on the assumption that the dose-toxicity curve remains flat and that the time to a DLT is constant. However, these models require more assumptions than a 3+3 design and can take longer to complete. These models have also been shown to outperform the 3+3 design in terms of safety and reliability.


The traditional 3+3 design is the prevailing dose-finding method for phase I oncology trials. This rule-based design does not require modeling of the dose-toxicity curve and is relatively simple to implement. In addition, the accrual of three patients per dose level provides information about pharmacokinetic interpatient variability. However, the use of this trial design has some significant drawbacks. For example, it leads to a large proportion of patients being treated at low (ie, potentially subtherapeutic) doses while few receive the recommended phase II dose.

The use of the 3 + 3 design has been questioned due to its poor statistical properties, its lack of flexibility to target alternate DLT rates and its limited duration of observation. As a result, the conventional approach often selects a dose that can be unacceptably toxic when it is studied in larger groups of patients. Alternative trial designs are needed to identify the optimal dose for cancer vaccines. These include the interval i3+3 and mTPI-2 designs.

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Unlocking Digital Playgrounds: 메이저놀이터 Explained

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Discover the World of Dutch Design at Our Outlet

Dutch Design Moubels

Dutch Design is a world-class label that stands for both design classics and new innovative creations. Its heritage goes back to the works of De Stijl architects Gerrit Rietveld and Mart Stam as well as Marcel Wanders’ Knotted Chair from 1996.

Dutch Design is characterised by its minimalistic eenvoud and innovative ontwerpen. Come and discover the creations of Dutch designers at our outlet!


Dutch design is world famous and characterized by its minimalist, experimental, innovative and non-conventional approach with a touch of humor. It also emphasises functionality and practicality. Dutch design is also renowned for its high quality and a keen eye for detail, which is why dutch design meubels are often made locally, in the Netherlands.

Whether you’re looking for a classic wooden bank or modern metal cabinet, at Mobiel Interieur you’ll find the perfect match. Our experts are always on hand to support you and inspire you in your search for the perfect Dutch design piece for your home. We offer a wide selection of beautiful and functional Dutch design banks, cabinets, tables, stools and more from well-known brands such as Studio Mieke Meijer, Tom Frencken, Walewijn Grondman, Klaas Kuiken and Jasmin Djerzic. Discover the full collection of our Dutch designers here.


Dutch Design is a style of interior design that is characterized by simplicity and comfort. It uses natural materials, neutral tones, and plenty of plants to create a space that feels warm and inviting. This style also emphasizes minimalism and focuses on blending traditional elements with contemporary pieces to create a unique look.

In this year’s Dutch Design Week, many designers focused on sustainability and social responsibility. Solar designer Marjan van Aubel, for example, used her Sunne solar lights in an atmospheric installation that demonstrated the different cycles of daytime.

Are you interested in adding Dutch Design to your home? Check out our collection of Dutch Design furniture online or visit our showroom in Zevenaar. Our team will be happy to help you find the perfect piece for your home. Our showroom is open 7 days a week, and you can always contact us if you have any questions. We pride ourselves on our vast knowledge of the market and our extensive experience in interior design.


Whether you’re looking for Dutch Design meubels for your woonkamer, slaapkamer of keuken, Gimmi has the perfect collection for you. In our online shop you’ll find a bijzondere selectie of design meubels from bekende en talentvolle Nederlandse ontwerpen en merken. In our showrooms in Zeist, Keulen en Milaan, hebben wij een bijzondere selectie van collecties met duurzame hekelen.

Onze webshop en showrooms zijn exclusief voor Dutch Design. Koop je in de online shop of kom langs in onze showroom van 4.000m2!

Als liefhebbers en expertes in het gebied van meubelontwerp en productie in Nederland hebben we veel meer plezier aan het verkrijgen van het natuurlijke, vrijgevochte kwaliteit en heerlijk comfort. We producen de meubels op uw wijngevangen met natuurlijke en duurzame kunstmatige materielen, waarbij we vele voor het aanwezigheid en heerlijke comfort het huis voelen. Het resultaat is een mooie, hoogwaardige en heerlijke interieur met subliem comfort.


Dutch Design is famous for its eenvoud, out of the box ontwerpen. Especially in this year, the Dutch designers are focussing on a shake-up of existing systems and hierarchies. They want to make us think about what we are consuming and where the future of our planet is going.

We are proud to be a member of this movement and support its values. In our showroom you will find a broad selection of designers who are working on a changing world with innovative, functional and elegant design. From the strakke design kast van Studio Mieke Meijer, to the functional but playful ontwerpen of Tom Frencken. Or choose for the stoelen of Walewijn Grondman, Klaas Kuiken or Jasmin Djerzic in combination with voor de kleurrijke humoristische woonaccessoires van Foekje Fleur.

Do you want to add a touch of Dutch Design to your interior? Then come and visit our showroom in Andijk. We will be happy to advise you!

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The Ultimate Design Event in Northern Europe

Dutch Design Week Tickets

Dutch Design Week (DDW) is Northern Europe’s largest design event and emphasises innovation and experimentation. Over nine days more than 2,600 designers present their work and ideas at locations throughout the city of Eindhoven. This includes exhibitions, lectures, prize ceremonies, networking events and debates.

With a DDW ticket you can access all locations free of charge. A DDW Pro Ticket includes additional discounts and perks.

Ticket price

Dutch Design Week is a nine-day event that takes place in October each year. It features exhibitions, studio visits, workshops and seminars at venues throughout the city of Eindhoven in the Netherlands. It is one of Europe’s largest design events and attracts thousands of visitors each year. The expositions are organized around a theme, and many of them are accessible to anyone.

The People’s Pavilion, for example, is free and is a great spot to visit with kids. It is located in the Strijp-S area and features innovative projects from designers around the world. Some are incredibly instagrammable, such as the “We Know How You Feel” installation that uses lasers and biosensors to show your emotions.

The DDW Music program is also a highlight of the festival. It features live concerts at various locations throughout the city. DDW also partners with venues like pop venue Effenaar and classical music venue Muziekgebouw Frits Philips to host concerts during the week.

Ticket types

DDW is the largest design event in Northern Europe, connecting designers from all over the world. It features exhibitions, lectures, prize ceremonies, networking events, and debates. Each year, thousands of visitors visit Eindhoven to experience the designs on offer. IDE’s projects are featured at many of the in-person and online events, including Design United’s Up Close and Personal week and CLICKNL’s DRIVE Festival.

A DDW ticket gives you full nine-day access to all locations and areas. It also includes the DDW Design Rides. You can plan your route based on one of the programme lines or opt for a guided tour.

You can buy tickets for individual locations / expo’s such as Kazerne (EUR 5), Dutch Invertuals (EUR 5), New Order of Fashion Lab (EUR 2,50) or Philips Museum (EUR 11). DDW Pro Tickets are available for companies. These include a wristband for everyone who works in your organisation and a numbering system to help you find your location.

Ticket discounts

Dutch Design Week is a nine-day event featuring exhibitions and events at more than 120 locations in Eindhoven. The festival is an important platform for new designers and a showcase of Dutch design. In addition to the in-person events, DDW also hosts a range of online projects and initiatives. This year, TU Delft is represented in multiple online and in-person events, including Design United’s Up Close and Personal and the DRIVE Festival.

Many e-commerce websites offer discounts to military members as a way of showing appreciation for their service. These discounts can range from markdowns to free shipping. However, the specifics of these offers can vary from site to site, so it is best to check out each website’s individual terms and conditions.

Customers can save on delivery costs by signing up for an e-commerce website’s newsletter. This will usually provide them with a list of available promotions and deals. In addition, they may receive exclusive discounts and special offers that aren’t available to the general public.

Ticket information

Dutch Design Week (DDW) is one of the biggest design events in Northern Europe, attracting designers and enthusiasts from around the world. The event showcases innovation in a variety of design disciplines, including industrial design, fashion, and architecture. It also offers a glimpse into the Netherlands’ rich cultural heritage and progressive mindset.

During DDW, over 2,500 designers showcase their work in more than 110 locations across the city. This includes exhibitions, lectures, prize ceremonies, networking events, and festivities. The event also promotes interdisciplinary dialogue between designers and other professionals.

Although the majority of DDW venues are free, some require tickets or reservations. The official DDW website lists all ticketing information, including how to buy and use them. You can also purchase a special DDW Pro Ticket for 170 euros, which gives you discounts on talks and access to locations that are closed to the public. For example, you can visit the Klokgebouw, Microlab Hall, Design Academy Eindhoven Graduation Show, and Thing Nothing at Van Abbemuseum.

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Revolutionizing Gaming with Evolution Powerball Relay

Embracing the Evolution Powerball Relay in Gaming

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The Evolution of Powerball Broadcasting: Unveiling the Phenomenon

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The Diversity and Innovation of Dutch Design

What Is Dutch Design?

Designers from the Netherlands are becoming increasingly well-known abroad. When the design world hears the name Dutch Design, they may picture the innovative furniture pieces of designers like Droog or Mooi or the avant-garde designs by Richard Hutten and Marcel Wanders.

Others might think of Gerrit Rietveld’s Red Blue Chair or the experimental graphic designs by Wim Crouwel. Yet, the true face of dutch design is much more varied than this.

De Stijl

A synthesis of various influences, Dutch design has become an internationally recognized phenomenon. Rather than eliminating, it chooses to selectively add elements, creating a curated space that is uniquely suited to the people living in it.

The De Stijl movement, founded by Piet Mondrian and Theo Van Doesburg in 1917, was an art and design movement based on strict ideals of horizontal and vertical geometry and primary colors. Their work was influenced by Neoplatonic philosophy and ideas developed by mathematician Dr. M.H.J. Schoenmaekers, who claimed that “yellow radiates, blue recedes and red floats.”

The De Stijl artists believed that the world was becoming more and more industrialized, and that art should reflect the simplest, most universal aspects of nature. After the horrors of the first world war, they hoped to create a utopian vision of the future based on pure abstraction and universal harmony. However, this utopian ideal was never fully realized as Mondrian broke away from the group in 1923 when Van Doesburg introduced diagonal elements to his work, a concept that Mondrian viewed as artistic heresy.

Marcel Wanders

During the 17th century, the Netherlands achieved unprecedented economic and cultural success. The enduring impact of this period can be seen in the art of Rembrandt and Vermeer. Similarly, the work of designers such as Bovenkamp, Galvanitas, Hala, Fristho, and Raak have become synonymous with Dutch design.

Marcel Wanders, the first designer to use staged photography in his poster work and credited with the revival of De Stijl, has since founded several design companies including Moooi where he serves as creative director and co-owner. His designs have won numerous awards and are displayed in museums worldwide including the Museum of Modern Art in New York and San Francisco, the Stedelijk Museum in Amsterdam, the Van Abbemuseum in Eindhoven and the Central Museum in Utrecht.

The legacy of these and other influential Dutch designers can still be seen, albeit in a mutated form, in the work of today’s younger generation of homegrown creatives. One such is Lex Pott, who combines traditional materials and techniques with contemporary technology to create entirely new products such as his Transience mirrors that manipulate the natural process of oxidation.

Richard Hutten

Known for his conceptually innovative yet playful designs, Rotterdam based designer Richard Hutten graduated from the Design Academy Eindhoven in 1991 and started his own studio shortly after. He has since become one of the leading international figures in his field, and is represented in over 40 museums worldwide.

Hutten is a key exponent of the Dutch ‘Droog Design’ movement, which has changed the world of furniture since its beginnings in 1993. His work is characterized by the idea of playfulness and a reference to Homo Ludens or ‘Playing Man’.

Another modern Dutch designer is Lex Pott, who manipulates natural processes to create new products. His Transience mirrors, for example, use the natural oxidation process of glass to create bold geometric patterns. The result is a reflection of the changing environment in which we live, and illustrates the way in which designers are working to adapt their products to this. The result is a unique collection that is both functional and artistic.

Studio Wieki Somers

It’s easy to see how these innovators left a lasting impression on modernism, and their legacy can still be seen in the work of contemporary Dutch designers. Some are taking their inspiration even further.

For example, Studio Wieki Somers’ Merry-Go-Round Coat Rack combines the practicality of a coat rack with artistic flair and a sense of wonder. The outermost rings take their colour palette from the sun, while the inner ones are synchronised with the moon’s phases.

Another example is Lex Pott’s Transience Mirrors, which use natural processes like oxidation to create a series of bold geometrical patterns that reveal the aging process of the mirrored glass. Meanwhile, Studio Moniker applies a similar philosophy to information design. They use graphic design to turn complex fields of data into visually intelligible form. They also design books, atlases and other forms of documentation. These designers are reimagining the role of design, and their work is gaining both informal and formal international acclaim.

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Unleash the Excitement of Live Football Broadcasts

Discover the Thrills of 축구중계

If you’re a sports fan or a football aficionado, you may have heard of an exciting practice known as . But what exactly is this, and why is it becoming incredibly popular among sports enthusiasts?

What is 축구중계?

Essentially, 축구중계 is a Korean term that refers to football broadcasts. This refers to the practice of transmitting soccer games live, either on television, radio, or the internet. Whether you are a hardcore soccer fan or a casual viewer, the excitement that brings is hard to match.

Why is 축구중계 Popular?

The rise in popularity of 축구중계 can be attributed to the ubiquity of the internet. With the world becoming increasingly digital, more people can now access live football games from the comfort of their homes. Additionally, the international appeal of soccer makes 축구중계 a thrilling experience for fans around the globe.

The Benefits of 축구중계

One significant advantage of 축구중계 is its convenience. You don’t have to physically be in a stadium to enjoy a thrilling football match. All you need is a reliable internet connection and a device to watch, and you’re good to go. Plus, with 축구중계, you can get real-time updates and commentary, making the viewing experience even more exciting.

Navigating the World of 축구중계

Though 축구중계 is an incredible experience, it can be overwhelming, especially if you’re new to it. It’s essential to find reliable sources for live broadcasts, stay updated with match schedules, and understand the game basics to fully enjoy the experience.


In conclusion, 축구중계 is a fantastic way for football fans to enjoy the game, regardless of geographical or physical restrictions. Convenience, real-time updates, and the sheer excitement of live games make 축구중계 a must-try for every football fan out there.

Frequently Asked Questions

1. What does 축구중계 mean?
– 축구중계 is a Korean term that refers to football or soccer broadcast.

2. How can I watch 축구중계?
– You can watch 축구중계 on various platforms like television, online streaming sites, or radio broadcasts.

3. Why is 축구중계 popular?
– The popularity of 축구중계 can be attributed to the convenience it offers. Fans can enjoy football games without leaving their homes.

4. Do I need any special equipment to watch 축구중계?
– All you need to watch 축구중계 is a reliable internet connection and a device such as a smartphone, computer, or TV.

5. Can I watch international football games through 축구중계?
– Yes, most 축구중계 platforms provide access to both local and international football games.