Analysis of Clinical Trial Length – Nature Drug Discovery

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How can we explain the duration of clinical trials?

A recent Nature Drug Discovery article written by L. Pregelj & her colleagues from the University of Queensland (Australia) found a solution with a multiple-regression model partially explaining the variation in clinical trial length. The controlling factors included trial primary purpose, end point classification, trial size, therapeutic class, geographic location, type of sponsoring organization.

Sample characteristics: trials started between 2005 and 2009, registered at ClinicalTrial.gov by February 2013. Total number of trials analyzed: 14’319 (Phase I, II or III)

A first view on the trials shows that:

– the numbers of individual trials registered each year rose;

– the length of these trials initially decreased across all phases.

But more details are needed to have better view of the real factors impacting the duration of clinical trials.

The authors built a model to assess whether the changes in clinical trial length depend on trial design specificities (primary purpose, phase, size, allocation,…), therapeutic class (anti-infectives, cancer drugs, cardiovascular medicines, CNS products, metabolics,…), geographic location, type of sponsoring organization (Government vs. Industry) or a combination of some of these factors

The results:

– overall mean length (unweighted): 21.6 months.

2 key factors influencing clinical trial length: type of sponsoring organization and therapeutic class. The trend for length is flat for the pharma industry meaning greater experience and knowledge enabled the companies to build efficiencies but further improvements will be difficult to achieve with standard trial design. The trend is decreasing for US Federal sponsored trials suggesting that best practices began to diffuse beyond the industry itself.

– despite the fact that the stage of the trial (Phase I, II or III) was not one of the two major factors contribution to the length of a clinical trial, the influence of this factor increased significantly in the recent years.

These results are surprising somehow as you would anticipate to have the stage of the trial as a major contributor to its length but the therapeutic class and the sponsor are far more important.

Nature Drug Discovery Article (Subscription required)

Nature Drug Discovery Supplementary Material

More resources:

Better Clinical Trial Designs Could Lower Development Costs And Yield More New Drugs – 2014- Forbes

Understanding Clinical Trials – 2013- An overview provided by Roche

An Overview of Bayesian Adaptive Clinical Trial Design – 2012 – Berry Consultants

Adaptive design clinical trials: Methodology, challenges and prospect – 2010 – Indian Journal of Pharmacology

 

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How to determine R&D’s productivity – McKinsey

Test tubesMcKinsey experts led by Eric Hannon, worked on a unique formula to help innovative companies value the productivity of R&D activities

They explained the issues in trying to estimate the performance of R&D. Some ratios like R&D in % of sales as well as the % of new products launched over the last two years can be used but unfortunately they are not capturing the reality.

They worked on this challenge, designed a unique formula and tested it in real corporate life.

The approach

R&D outcomes = multiplying a project’s total gross contribution by its rate of maturation and then dividing the result by the project’s R&D cost.

The advantages

1. A single metric

2. Goal to measure what R&D contributes within the sphere of what R&D can actually influence

3. By measuring productivity both at the project level and across the entire R&D organization (through simple aggregation), it endeavors to speak to the whole company

The ratio & its key components

McKinseyRDRatio

Total gross contribution is the product’s economic value to customers. It is best calculated, I think, with a NPV.

Achieved product maturity is how close it is to verifying and validating its technical and commercial requirements. The implication is that companies must be able to assess, in real time, how close their R&D projects are to full maturity (simply looks at critical dimensions (such as cost, functionality, and quality) during each of the quality gates a project passes through in its development).

For pharma companies, I think that the numerator of the formula could be the rNPV for a specific project (or the aggregation for all the projects of the company). Have a look at my lectures on valuation if you would like to find out more about rNPV.

Consumed R&D costs are easy to find.

Management impact

This formula will help the management in several fields:

1. Setting direction

2. Improving teams

3. Making objective décisions

4. Driving change

McKinsey Article

Other resources:

Is R&D earning its investment? – 2010 – Deloitte

Measuring the return from pharmaceutical innovation – 2014 – Deloitte

How to create value for drugs? Comparative effectiveness and improved patient consideration – Office of Health Economics

microscopeFuture expectations for new drugs – 3 new papers written by the experts from OHE

A series of three articles exploring future expectations for new drugs of evidence of relative effectiveness in Europe and comparative effectiveness in the USA in 2020 have been published in the Journal of Comparative Effectiveness Research.

In a value-based and outcomes-based health care environment, there is a mandatory requirement for pharmaceutical companies to demonstrate the value of their products not vs. placebo but vs. the current standard of care.

Key questions must be answered:

Market Access

Source: Bridgehead Oncology Workshop, London 2012.

As mentioned in our page on Strategy & Vision, an increasing focus and trend toward value-based healthcare initiated by M. E. Porter will really make a difference for our health systems. We will stop paying for me-too products and pay only for value-added products that will bring real outcomes for all the stakeholders.

We will also probably be much more patient-centric in the future and use patient value to better select relevant projects as described by Stuart Dollow in his recent blog post on Prioritising Projects by Predicting Patient Value. Considering the patient as a partner and valuing his/her opinion to target precisely his/her needs as well as the clinical requirements will push the pharmaceutical industry toward more value generation because of the integration of the related stakeholders in the development process.

OHE Article (where you can access all the articles and working papers) – To download working papers you have to register (it’s free).

Direct Access to the Articles

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How Big Pharma GlaxoSmithKline is managing its R&D Collaborations – Xconomy

SanDiego

Being close to scientific innovators is key

Cambridge and San Diego are two main centers for innovation in life sciences, according to GlaxoSmithKline. Actually the big pharma established a “first-of-its-kind collaboration” with San Diego’s Avalon Ventures in 2013; lastly it has opened a small office in San Diego to manage its R&D partnerships and to prospect for more deals on the West Coast. GSK also set up a similar outpost in 2014 in Kendall Square, the Cambridge, MA, neighborhood that has become the pharmaceutical industry’s East Coast hub and is close to Harvard, MIT, and the Broad Institute.

Xconomy article

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Finding success in failing early – Life Sci VC

Fast fail is the best advice for any biotech company

Entrepreneurship

This blog post comes from one of my favorite blog about life sciences. Killing early unsuccessful projects is necessary to ensure a better long-term vision for the whole company. Observations and lessons: 1. Think about the end at the beginning; 2. Team spirit with truth-seeking mentality; 3. Sooner rather than later; 4. Listen to the market.

Life Sci VC Blog post

New ‘Molecule-Making Machine’ Could Speed The Development Of Life-Saving Drugs – Huffington Post

3-D printing at a molecular level could lead to advances in drug development but not only…

A very interesting discovery made by Dr. Martin D. Burke, a professor of chemistry at the University of Illinois at Urbana–Champaign. Why is it a revolution?

The traditional way of synthesizing small molecules requires a step-by-step series of chemical reactions–a process that is time-consuming and which requires enormous expertise. The new printer simplifies the molecule-making process and makes it accessible to non-chemists.

Read the article

A Faster Way to Try Many Drugs on Many Cancers – NYT

A new way to give hope to patients

doctor_physician_surgeryCancers often tend to be fueled by changes in genes, or mutations, that make cells grow and spread to other parts of the body. There are now an increasing number of drugs that block mutations in cancer genes and can halt a tumor’s growth.

While such an approach has worked in a few isolated cases, those cases cannot reveal whether other patients with the same mutation would have a similar experience.

Now, medical facilities are starting coordinated efforts to find answers. And this spring, a federally funded national program will start to screen tumors in thousands of patients to see which might be attacked by any of at least a dozen new drugs. Those whose tumors have mutations that can be attacked will be given the drugs. The studies of this new method, called basket studies because they lump together different kinds of cancer, are revolutionary, much smaller than the usual studies, and without control groups of patients who for comparison’s sake receive standard treatment.

The NYT article

Training on trials: Patients taught the language of drug development – Nature Medicine

The European Patients’Academy on Therapeutic Innovation (EUPATI) provides information and resources to patients

PatientThe European Patients’ Academy on Therapeutic Innovation (EUPATI), a consortium of 30 organizations from around Europe dedicated to providing information and resources on the medical research and development process to people affected by disease. The expert training course is designed to teach patients—current and former—or family members of patients all about the clinical trial process, from preclinical research and development all the way through the clinical trial and approval pipelines. The hope is that trainees will go on to become actively involved in the clinical research and development process—whether it’s by working with pharmaceutical companies or serving on regulatory agencies’ committees—or to serve as resources for other patients confronted with similar problems.

The Nature Medicine Article

Treat infections with artificial viruses – The Economist

Very interesting article on bacteriophages

LambdaPhageViruses that will attack bacteria. Renewing interest in phages could probably help tackle resistant bacteria. It is not new but has been forgotten for a long time… Some Western researchers are believing in phages, hoping, with modern methods, to turn them into tailored treatments for infection.

Read the article in The Economist    More on Phages    More on the company Synthetic Genomics

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Antibiotic Resistance Could Kill Us All: Here’s How To Stop It – Fast Company

BlisteredPillsThe war between new drugs and mutated bacteria – who will win in the future?

Antibiotics have saved countless lives in the last 80 years, but they’re not as effective as they once were. We use too many of them, and so bacteria are developing resistance more quickly than we can come up with new drugs. Why are we using too many of them? Because they are too cheap. We even use antibiotics to make cattle grow faster… The price of the new antibiotics should be much higher to discourage their use in farms and protect human health.

Fast Company Article

Cancer Immunotherapy Companies: Looking Forward and Looking Back – Xconomy

Cancer immunotherapy successes and failures with very good examples: Dendreon and Juno Therapeutics

packs_of_pillsWhat scientific, legal, and business challenges does the immunotherapy companies face? Stewart Lyman looks at some of them: intellectual property concerns, technology issues, huge manufacturing costs, pressures on pricing and reimbursement, obsolescence and limited patient populations. Find out more

AstraZeneca Launches USD 40m Early-Stage Anti-Infectives R&D Unit – GEN News

AstraZeneca will spin-off its anti-infectives R&D unit

test-214185_1280AstraZeneca will spend USD 40 million to create a new stand-alone subsidiary focused on early-stage research and development of small molecule anti-infectives. AstraZeneca is one of the big Pharma, together with Roche, that is focusing on the development of new solutions for drug-resistant bacteria. Read more

How to Develop New Antibiotics – New York Times

Why is it key to rethink antibiotics development?

EHEC Outbreak Claims 11 LivesHere’s a very compelling article written by about it.

THE bacteria are winning. Every year, according to the Centers for Disease Control and Prevention, at least two million people are infected with bacteria that can’t be wiped out with antibiotics, and as a result, 23,000 people die. Direct health care costs from these illnesses are estimated to be as high as $20 billion annually. Read more