NHS Dorset clinical commissioning group: leadership award runner-up

Clinical leads from Dorset CCG. The Great Leaders programme has helped family doctors to speak authoritatively about their work and priorities. Photograph: Dorset CCG/Columbia Photography

The Great Leaders programme developed for GPs in Dorset has given them the confidence they need to take on their new role as NHS commissioners, with responsibility for a £900m budget and a 766,000 patient population.

The scheme, which involves 40-50 GPs who have lead roles in the county-wide clinical commissioning group (CCG), has also made family doctors more "media savvy", so that they can speak authoritatively and clearly about the work they are doing and their priorities.

Since the programme was launched in June last year, the GPs involved in it have increased their public profile. They were behind an awareness campaign concerning when the public should use the new 111 out-of-hours telephone advice line and they also launched The Big Ask public consultation exercise seeking patients' views about local services.

GPs also organised two large public meetings to invite comments about the CCG's strategy.

On the commissioning front, the GPs were instrumental in introducing new dementia services following negotiations with their local authority health and wellbeing boards. They have also lad on commissioning services that help avoid emergency hospital admissions, as well as others such as targeting chronic obstructive pulmonary disease services in the over-75s and establishing a community-based pain management service.

The CCG's director of engagement and development, Charles Summers, says the list of achievements illustrates the success of the programme, as the GPs have moved from taking responsibility for the care of their own practice list to having responsibility for a county-wide population.

Having confident GP commissioners has also changed the focus of conversations with providers for the better. "It's now about 'how can your contract support me and my patients?', often in the past those conversations have been financially lead," says Summers.

This article is published by Guardian Professional. Join the Healthcare Professionals Network to receive regular emails and exclusive offers.

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Alnylam Pharmaceuticals' CEO Discusses ALN-TTRsc Phase I Clinical Data (Transcript)

Executives

Cynthia Clayton - Vice President, Investor Relations and Corporate Communications

John Maraganore - Chief Executive Officer and Director

Barry Greene - President and Chief Operating Officer

Akshay Vaishnaw - Senior Vice President and Chief Medical Officer

Analysts

Geoff Meacham - JPMorgan

Alethia Young - Deutsche Bank

Marko Kozul - Leerink Swann

Alan Carr - Needham & Company

Ted Tenthoff - Piper Jaffray

Stephen Willey - Stifel

Alnylam Pharmaceuticals, Inc. (ALNY) ALN-TTRsc Phase I Clinical Data Conference Call September 23, 2013 8:00 AM ET

Operator

Welcome to the Alnylam Pharmaceuticals conference call to discuss interim clinical results from their ALN-TTRsc Phase I trial. (Operator Instructions) I would now like to turn the call over to the company.

Cynthia Clayton

Good morning, everyone. I am Cynthia Clayton, Vice President of Investor Relations and Corporate Communications at Alnylam. On the call with me today are John Maraganore, our Chief Executive Officer; Barry Greene, President and Chief Operating Officer; and Akshay Vaishnaw, Executive Vice President and Chief Medical Officer.

For those of you participating via conference call, the slides we have made available via webcast can also be accessed by going to the Investors page of our website, www.alnylam.com.

During today's call, as outlined on Slide 2, John will provide some context on our ALN-TTRsc clinical results and what they mean for the program Alnylam and for the RNAi field. Akshay, who is on the call remotely, will then review the results of the ALN-TTRsc clinical study. Barry will review our upcoming milestones, and we will then turn the call over to you for your questions.

Before we begin, and as you can see on Slide 3, I'd like to remind you that this call will contain remarks containing Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent quarterly Report on file with the SEC.

In addition, any forward-looking statements represent our views only as of the date of this recording, and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements.

I will now turn the call over to John.

John Maraganore

Thanks, Cynthia. Welcome, everyone, and thanks for joining us this morning. As you can imagine, we are very excited to share with you these positive clinical data from our ALN-TTR subcu Phase I study.

These human data are the first to be presented for our proprietary GalNAc-siRNA conjugate delivery platform, which enables subcutaneous dosing of RNAi therapeutics with a wide therapeutic index. These new clinical results clearly establish human translation for RNAi therapeutics that utilizes delivery platform.

Moreover, we believe these new results demonstrate an unmatched level of efficacy for RNA therapeutics with a consistent approximately 90% target gene knockdown via subcu dose administration, in addition to a very promising safety profile. More specifically to our TTR amyloidosis program, we believe these results establish a new benchmark for consistent and sustained TTR knockdown of approximately 90% for RNA therapeutics in development for ATTR.

Because of results like these, our GalNAc-siRNA conjugate delivery platform has now become our primary approach for execution on our Alnylam 5x15 product strategy and in addition to our TTR cardiomyopathy program, it is the platform we're using in our programs in hemophilia, porphyria, complement-mediated diseases, hypercholesterolemia, beta-thalassemia and alpha-1-antitrypsin deficiency, amongst others programs that are yet to be disclosed.

As a result, these data are very meaningful, not only for the continued advancement of ALN-TTRsc, but also for the continued execution on our entire Alnylam 5x15 product strategy. Through this strategy, we believe that we are building a compelling opportunity for shareholder value creation with a modular and reproducible approach for development and ultimately commercialization of innovative medicines for genetically defined disease.

We are in the midst of very exciting times at Alnylam with a steady flow of free clinical and clinical data. And these new results reflect the strong potential of RNAi therapeutics to become a whole new class of innovative medicines.

I'll now turn the call over to Akshay, for a more detailed review of the data. Akshay?

Akshay Vaishnaw

Thanks, John. As you just heard, these new ALN-TTRsc results represent a major milestone in our ATTR program as well as our entire pipeline of RNAi therapeutics. We believe this level of consistent TTR knockdown is exceptional and unmatched. And we now aim to advance ALN-TTRsc in future clinical studies with the goal of achieving approximately 90% TTR knockdown to maximize clinical efficacy.

As most of you are aware, our ATTR program is our lead 5x15 program. ATTR is a devastating, often fatal, hereditary orphan disease caused by mutations in TTR gene afflicting approximately 50,000 people worldwide.

There are two clinical presentations of ATTR. These include familial amyloidotic polyneuropathy or FAP, which affects approximately 10,000 people globally; and familial amyloidotic cardiomyopathy or FAC, which affects at least 40,000 people worldwide. Of course many patients also show evidence of mixed nerve and heart involvement.

New therapies are clearly needed for the treatment of ATTR, and we believe that our mechanism of action, silencing of the disease causing TTR gene leading to knockdown of the circulating pathogenic TTR protein has the potential to generate a profound therapeutic impact.

Now let me walk you through our ALN-TTRsc Phase I study and the results we have generated to date. As you can see over Slide 10, the Phase I trial is being conducted in the U.K. as a randomized, double-blind, placebo-controlled, single and multi-dose, dose-escalation study, enrolling up to 40 healthy volunteer subjects. The primary objective of the study is to evaluate the safety and tolerability of single and multiple doses of subcutaneously administered ALN-TTRsc.

Secondary objective include assessment of clinical activity of the drug as measured by serum TTR levels. In an initial single-ascending dose phase of the study, subjects receive subcutaneous doses of placebo or ALN-TTRsc from 1.25 mg to 10 mg/kg. In the multiple-ascending dose phase of the study, subjects receive 10 subcutaneous doses of placebo or ALN-TTRsc from 2.5 mg to 10 mg/kg.

As you can see on the Slide 11, interim data from the 28 subjects enrolled and analyzed in this study to date, showed that single and multiple dose administration of ALN-TTRsc resulted in rapid, dose-dependent, consistent and durable knockdown of serum TTR levels.

In the multi-dose cohorts, there was a statistically significant knockdown of serum TTR at all doses tested as compared to placebo. At a dose of 5 mg/kg, ALN-TTRsc administration resulted in up to 93.3% knockdown of serum TTR and a mean TTR knockdown of 87.5% at nadir. At a dose of 10 mg/kg, ALN-TTRsc led to up to 94% knockdown of serum TTR and a mean TTR knockdown of 92.4% at nadir.

By all accounts, this is an exceptional and unmatched level of TTR knockdown. Notably, during the period of dose administration, TTR levels are essentially clamped down showing a very consistent effect during dosing. In addition, we are very pleased to see a very rapid onset of action, with nadir achieved at about day 50, and then a very durable effect after cessation of drug with recovery to baseline levels at several weeks after.

And on the inside of Slide 11, analysis of TTR knockdown in humans as compared to non-human primates shows there's a highly correlated effect between the two species on a milligram per kilogram basis. Importantly, as John said, we believe these results unambiguously confirm human translation for our GalNAc-siRNA conjugate platform.

Now, our Phase I study is ongoing and we're currently enrolling subjects in additional cohorts to explore the activity of ALN-TTRsc administered weekly at a dose of 7.5 mg/kg as well as administration of ALN-TTRsc on once every two week dosing schedule. We'll use these additional data to finalize our dose and dose regimen selection for the start of our Phase II later this year with the start of our Phase III plan for next year, but we expect to be proceeding with either a 5 mg/kg or 7.5 mg/kg weekly or once a week two-week dosing regimen.

Setting up safety in this study, as reported to date, single and multiple doses of ALN-TTRsc were found to be generally safe and well tolerated. There were no significant or serious adverse events associated with the drug at doses through 10 mg/kg.

As detailed on Slide 12, all adverse events would be mild or moderate in severity. Injection site reactions were observed in the minority of subjects, including those receiving placebo. These are reported as being clinically mild and consist of transient erythema associated in minority of cases with edema or pain.

In all cases, these reactions were self-limiting and results completely typically within two hours of onset. Importantly there were no study discontinuations, flu-like symptoms or changes in cytokine, CRP, liver function test or kidney function or hematologic parameters.

In aggregate, these new data support our conviction that ALN-TTR has the potential to be an important therapeutic for the treatment of familial amyloidotic cardiomyopathy, a disease for which there are no approved therapies. Clearly, the ability of RNAi therapeutic to achieve a consistent approximately 90% knockdown of serum TTR sets a new benchmark that I believe has the potential to translate into meaningful clinical benefit for patients.

With these results in hand, we are well-positioned for continued execution on this program, which includes the initiation of a pilot Phase II study in FAC patients by the end of this year, and assuming positive results start of a pivotal Phase III trial with ALN-TTRsc by the end of 2014.

And with that, I'd like to turn the call over to Barry. Barry?

Barry Greene

Thanks, Akshay, and good morning, everyone. As you've heard we are demonstrating with robust human clinical data that the RNAi pathway can be harnessed to create high-impact innovative medicines. These new data point out our GalNAc-siRNA conjugate delivery platform as our primary approach for execution on our Alnylam 5x15 product strategy.

As a result, these data are very meaningful, not only for the continued advancement for ALN-TTRsc, but also for the continued execution of our entire Alnylam 5x15 product strategy. And while we have made tremendous progress since the start of the year, we still have some very exciting preclinical and clinical data presentations and milestones coming out of the rest to the year, as you can see on Slide 16.

As Akshay mentioned, we remain on track to start a Phase II study with ALN-TTRsc in cardiomyopathy patients later this year and are planning to start a Phase III trial in 2014. Now, with regard to our TTR02 program, we expect to present further data from our Phase II trial at the International Symposium on FAP in Brazil in November. These data will include full TTR knockdown data for about 30 ATTR patients.

For patients enrolled in Phase II study, we aim to begin an open-label extension study as well in the coming weeks. This study will include clinical data that will begin to readout in 2014.

Finally, we plan to initiative a Phase III pivotal trial for ALN-TTR02 in polyneuropathy patients by the end of the year. Without a doubt, this continues an exciting transition for Alnylam, as we enter advanced stages of our clinical development with our lead program.

Now, turning to our ALN-AT3 program for hemophilia, we've also made tremendous progress and are on track to file an IND for this program in the fourth quarter of this year and a Phase I start in early 2014. With our ALN-AS1 porphyria program we expect to identify a final development candidate for the program by late 2013 and to advance into clinic in 2014.

We also plan to nominate a development candidate for our ALN-CC5 program for complement-mediated diseases by the end of this year. For ALN-CC5, we'll provide clinical timeline guidance at the beginning of next year, but you can expect us to move this program forward quickly. And we plan to end the year with greater than $320 million cash.

Finally, with a number of scientific meetings from now to the end of the year, where our scientists will be presenting new data from essentially all of our 5x15 programs. In summary, I think it's clear that we are executing on our goal of advancing RNAi therapeutics with a potential to become an entirely new class of innovative, high-impact medicines for patients in need.

With that, I'd like to turn the call back over to the operator for your questions. Ellie, we'll take questions now.

Question-and-Answer Session

Operator

(Operator Instructions) Our first question comes from Geoff Meacham of JPMorgan.

Geoff Meacham - JPMorgan

I had a few questions. I knew you guys hadn't reported ISRs with the IV formulation, at least I don't remember that, but you have that here. Do you think that for subcu, this is the administration itself or is it some mechanism for the GalNAc delivery or is this problematic at all when you guys look at taking subcu into Phase III down the road? And I have one follow-up.

John Maraganore

Geoff, as you know, just about every subcutaneously-delivered drug has injection site reactions as a reported AE that true with HUMIRA, it's true with insulin, it's true with low-molecular-weight heparin. So it is very much a common phenomenon with subcutaneously-delivered drugs.

With an intravenous infusion of course, there you don't typically have these type of reactions, because you go to a hospital, you get an intravenous catheter administered. So it's a very different type of procedure. None of these injections site reactions that we're seeing are in any way, shape or form limiting, in terms of how we think about that. And the drug will be forward. Akshay, do you want to comment any further on that.

Akshay Vaishnaw

Yes, and I think couple of things over that is that as we described these reactions are very transient, lasting a couple of hours and this consist generally of redness. And importantly no one discontinued, no one was bothered by them, no. Action needed to be taken. And so they are very much, as John is saying, in keeping with other subcu drugs, which have been very successful. And in an indication like this we see nothing but green lights with these great data that we have to knockdown up to almost 94%.

Geoff Meacham - JPMorgan

And then the follow-up is for ATCR. From you guys, epidemiology work, are the mutations at the, let's say the less or more severe spectrum of disease that you can use to inform the entry criteria, when you guys look to start your pivotal later on this year?

John Maraganore

Yes, that's a great question. Akshay, do you want to handle that?

Akshay Vaishnaw

Geoff, just repeat that. I didn't quite get the angle on your question. Are the mutations less or more severe?

Geoff Meacham - JPMorgan

At the spectrum that you can somehow narrow the population or inform your entry criteria for the pivotal study.

Akshay Vaishnaw

I mean the genotype/phenotype relationships are pretty well understood, Geoff. And so we are fortunate to have a loss of literature and through our network of KOLs that we work within the FAC space. The kind of lion's share of FAC in the U.S. is taken out by this mutation V122I, which is dominant in the African-American population. And then there is T60A, and then there are about four others that are associated with FAC. So there's about half-a-dozen mutations that are well described, and we'll inform the design of our Phase III study.

John Maraganore

And Geoff, I'll just add, that in the Phase II that we're about to start, we'll look at a range of different genotypes in that study. It's not going to be restricted to any given genotype. So that will give us some experience across different genotypes prior to starting Phase III.

Operator

Our next question comes from Alethia Young of Deutsche Bank.

Alethia Young - Deutsche Bank

Just a question on like, in the open-label extension study, are you guys planning on communicating like different points with FDA about your progress there or is there any opportunity for breakthrough or faster pathway to approval?

John Maraganore

Alethia, that's a great question. We'll obviously keep the close touch with the FDA if there are compelling clinical data, we certainly will consider it. We'll go to the FDA and talking about our breakthrough, but we have to see how the data merge. Clearly that study is going to start very soon. There will be clinical endpoint data that we read out.

Theoretically, we'll going to give you some more guidance on that when we start that study. But there will be frequent, let me not use the word frequent, there will be periodic reviews of data that come out of that and obviously that's going to help our overall accrual efforts. In our TTR02 Phase III effort, it will obviously been meaningful for physicians to also see how that's progressing. And we'll certainly look at those data in the context of our interactions with the FDA. Akshay, anything you do you want to add to that.

Akshay Vaishnaw

No, no, I think that's exactly right. That's exactly right. We are excited to get the study going and we start to getting paid.

Alethia Young - Deutsche Bank

I hope you don't mind, just one follow-up. The three doses for the next three cohorts, can you just tell me what they are again, please?

John Maraganore

You mean the additional cohorts in the phase, the current Phase I.

Alethia Young - Deutsche Bank

Yes.

John Maraganore

So we are looking at a couple of things really. One, is we wanted to explore 7.5 mg/kg dose in that which is intermediate between the 5 and 10. And anything that we want to explore is in every other week dosing regimens. If you look at our data in our presentation from the multi-dose kinetics, you will see that the levels are very suppressed, and they seem after dosing has stop to be quite durable and it does open up the question of whether or not we can also explore once every two week dosing subcutaneously with our drug.

So we want to explore that in these additional cohorts. And I believe the additional cohort that's there is just a bulk of numbers in the overall population, so it's sort of in the same context of what's right there. Akshay, anything to add to that.

Akshay Vaishnaw

No, no, I think that's right. These initial interim data given there is a lot of guidance on different doses of regimen we'll explore. And I think it will be exciting to do that over the next couple of months.

Operator

Our next question comes from Marko Kozul of Leerink Swann.

Marko Kozul - Leerink Swann

I'd also like to echo my congratulations on your continued progress. My first question has to do with efficacy of GalNAc as a delivery platform. Can you give us a preview of where you might be headed in terms of further improvements and refinements? I think in this current Phase I TTR subcu multi-dose experience, you dosed up to 10 mg/kg.

And back in 2012 at OTS and on Slide 5, I think of your presentation this morning you appear to be achieving meaningful knockdown in the 2 to 3 mg/kg range for AT3 and PCS in pre-clinical models. So can you give us a preview of further improvements on where you might be headed?

John Maraganore

Yes. Thanks, Marko, that's a great question. The ALN-TTR subcu is the first GalNAc conjugate that we took into development. And obviously, we've now seen some very exciting and impressive results. But as all things in science, with a vibrant research group like we have here, there are constant improvements that we're making in these platforms and if that -- the benefit of that has been accrued in programs like our PCSK-9 program and our AT3 program as highlighted on Slide 5 of the conference call deck.

And you can clearly see that we're achieving ED80 type knockdown at doses around 1 milligram per kilogram. So it's about a tenfold, almost a tenfold, maybe a little bit less than a tenfold improvement compared to ALN-TTRsc. So we expect with AT3, which is about to start our clinical testing. We expect to be seeing 80% knockdown levels and doses that are in the 0.5 to 0.75 mg/kg level, which is really quite impressive. And we would expect to see similar type of effects with other GalNAc conjugates in the future.

So just exciting progress in general, and obviously the other thing, Marko, I will say is when we look at non-human primate data now with our GalNAc conjugates like we presented ISTH for our antithrombin program. We now know that that's one-to-one correlation in humans, based on the data you've seen today. So it's very exciting to able to have the confidence around that translation. And we just expect that to continue.

Marko Kozul - Leerink Swann

And just a quick second question that has to do with safety, which appears pretty clean in the poster and slides this morning. When you have final results from this Phase I study, what additional safety info will we have?

John Maraganore

Marko, we'll just have additional patients to look at and obviously look at that in the totality of the existing data sets. But I think also we'll soon be patients with this drug. And we'll soon be generating additional data, both efficacy and safety in patient populations and you will be seeing some of those data next year.

Operator

Our next question comes from Alan Carr of Needham & Company.

Alan Carr - Needham & Company

One of them, can you give us an update on -- any update on regulatory discussions around the upcoming Phase III trial? And then also, I guess a bigger picture question around the safety database here, how many patients have you been in with IV and subcutaneous across each of these some different platforms? And then the third one to follow-up on a previous question, it looks like you're doing, if you got three more cohorts, is it 7.5 every week? And then the other two are 5 and 7.5 every other week?

John Maraganore

Let me answer the first one or the last one first, which is its 7.5 mg/kg in two cohorts weekly and then there is an additional cohort of 7.5 mg/kg every other week, is the current lineup of what we're doing into Phase I. And again those data, we'll likely present those data or report on those data some time next year.

But as it relates to the first question on the regulatory discussions for TTR02, I can tell you that they are extremely well. We're pleased with the feedback we've gotten thus far. We don't foresee any issue from where we stand today, in terms of how we will proceed with the protocol and stay tuned on final details of the design, when we're going to report on them. But I think that we're quite pleased with those discussions. Akshay, anything to add on that point.

Akshay Vaishnaw

No, I think that's exactly right.

John Maraganore

And then you're challenging me now on the second question to sort of actuarially come together with numbers for you. So let me give you top-of-mind numbers. Our TTRO2 Phase I study was around 19 patients as I recall the number and our TTRO2 Phase II study that's going to be presented -- the final results will be presented in November, is about 30 patients. Our TTR subcu Phase I study that we presented today is 28 subjects. And obviously by the end of the additional cohorts it will be an additional -- Akshay help me out here.

Akshay Vaishnaw

No, I was just going to jump in, John. When we did R&D Day in July and added up the numbers, then at that point we had about 175 patients and the subject exposed in a various systemic deliveries human studies that we've done, so from our liver cancer program, TTRO1, TTRO2, PCS and others. And so John was giving you individual numbers from some of those studies, but at that number will soon to approach to 100.

We've given over 500 doses of intravenous Lipid nanoparticle based drug over two years of dosing. And in this current TTRsc study we'll of course top-out at around 40 individual exposed. So we're getting to a significant database and as we progressively shared the safety and efficacy information, obviously we're excited about the profile emerging for our drugs, both IV and LMP from a safety and efficacy viewpoint.

Operator

Our next question comes from Ted Tenthoff of Piper Jaffray

Ted Tenthoff - Piper Jaffray

So I guess my question sort of gets back to sort of a higher level, and I love the fact that you have the optionality around the IV and subcu and are now entering into FAC as well. But maybe tell us a little bit about how you see the future treatment of FAP. And obviously this is going to be data-driven, but is this a disease where maybe less-severe patients will be treated with subcu or maybe patients will be on-boarded first with IV to get disease under control? With this really impressive subcu data, are we even going to need an IV dose? I mean I know this is probably a little bit early to be looking into the crystal ball, but how do you foresee ultimately treating this disease, which is probably more heterogeneous than most people realize?

John Maraganore

It's a great question. Barry you want to handle it.

Barry Greene

Ted thanks for the question and the crystal ball into the future. It's fun to think about the issue of having two commercially available drugs for these patients. And as you know, our plan is develop ALN-TTR02 for FAP and ALN-TTRsc for the cardiomyopathy patients, FAC.

As we think about due to two commercial products available for all ATTR programs, it's likely in the future that we will generate data that allows these products to be used in the future interchangeably. With good data that allows us to educate the physician population to the appropriate use perfect dose and frequency of the drugs.

From a pharmacoeconomic perspective the diseases allow the kind of orphan pricings that you expect, so it won't be any economic incentive to change paces from one to the other, it really will be what's best for a patient. And as you fully appreciate in the world of orphan diseases, once we have and are benefiting the patient with the treatment of our drugs, we want to keep them on our therapies for the rest of their lives.

John Maraganore

And just to add to that, Ted, I suspect that in the future some patients will have to continue receiving drugs intravenous infusion. Like to go to the hospitals, with their physician to receive drug, and then other patients will say, well, I like the concept of having a at-home subcu option, and that's what I'd like to do going forward. And so I think we're going to create optionality here for patients in the future. And obviously, most importantly have what really is the best-in-class program, and best-in-class therapies available for these patients.

Ted Tenthoff - Piper Jaffray

I think there's a lot to learn, but I think you guys are making great progress, so really exciting.

Operator

Our final question comes from Stephen Willey of Stifel.

Stephen Willey - Stifel

I may have missed this, but just to confirm, the 7.5 mg/kg dose that you are planning to use in these next couple of cohorts, that's a single subcu injection, correct?

John Maraganore

Correct.

Stephen Willey - Stifel

And I know you also looked at retinal binding in vitamin A. Just any color around that? Is that consistent with what we have seen?

John Maraganore

Just totally beautifully consistent with what we've reported before. There is just a one beautiful correlation between [ph] RVT and vitamin A knocks down with TTR knockdown as well. So Steve, let me just also provide one clarification point. So we are doing 7.5 mg/kg weekly, okay. But we do, because of volume of administration we are using two injections to achieve that dose.

Stephen Willey - Stifel

And the volume, it's associated with each injection?

John Maraganore

It's roughly 1.5 ml for each injection of that dose. And so at 5 mg/kg, it could be done as a single 2 ml injection in that case.

Operator

And with no further questions, I would like to turn the conference back over to John, for any closing remarks.

John Maraganore

Well, thanks everyone for joining us this morning. We're obviously very excited about the new data and the potential for the continued execution of this platform in our Alnylam 5x15 strategy. And we look forward to sharing more updates and there will be more updates with you in the weeks and months to come. So thank you very much. Bye, bye now.

Operator

Ladies and gentlemen, this does concludes today's conference. You may now disconnect and have a wonderful day.

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NeoStem: Understanding Research And Its Implications To Clinical Trials

On September 11, a report published in the European Heart Journal Advance Access essentially validated the workings of NeoStem's (NBS) Phase II AMR-001, or at least the approach that NeoStem is using. The report flew somewhat under-the-radar, because a few days later, a negative article on Seeking Alpha questioned AMR-001, and caused NeoStem's stock to fall drastically. As a result, I reached out to NeoStem's Chief Medical Officer and CD34+ cell specialist Dr. Douglas Losordo who clarified the controversy quite nicely and completely tore down the author's argument in this Instablog post.

However, the report in European Heart Journal was quite important to NeoStem, yet no one seemed to notice. One reason is likely because these research reports are written in a way that very few retail investors (or analysts) can understand. Therefore, once more, I reached out to the company, hoping that this seemingly positive research report can be summarized for investors to understand. Hence, here is a short Q&A with the company's PCT segment's CMO Dr. Andrew Pecora, and his take on the report.

Note: I have added a few notes (in bold) for clarification and for important points.

Nichols

How do the results of this study compare with other related studies that have released either final or interim data? From a size, safety, and efficacy point of view.

Dr. Pecora

Pretty much the same. All studies have shown that if an adequate number of CD34 cells are administered (either isolated or admixed with marrow) during the window phase after inflammation has subsided (days 5-12 post acute myocardial infarction (AMI) there is a consistent finding of increased LVEF, preservation of heart muscle function and less adverse remodeling. One study also showed significantly fewer clinical events. (Essentially, Dr. Pecora is saying that when trials are done correctly, and the threshold dose is used, the outcome is consistent, which also goes hand-in-hand with NeoStem's goal in its Phase II trial)

Nichols

Can you elaborate on the significance of this statement within the research report?

"There was no difference in LVEF improvement between patients treated with cell infusion ,7 days from primary PCI compared with =7 days (1.46%, 95% CI: 0.41 to 2.51 vs. 2.69%, 95% CI: 1.80 to 3.58, P 1/4 0.08). Furthermore, we found no difference in LVEF improvement comparing patients with number of injected mono- nuclear BMC of ,108 compared with = 108 (2.80%, 95% CI: 0.79 to 4.80 vs. 0.58%, 95% CI: 20.44 to 1.59, P 1/4 0.05), Table 2. Studies, using MRI as LV function assessment had a smaller treatment effect in LVEF when compared with non-MRI studies (0.16% 95% CI: 20.88 to 1.20 vs. 4.67%, 95% CI: 3.69 to 5.66, P, 0.001)."

Dr. Pecora

This is a meta-analysis so data of this kind will not pick up small differences and probably cannot be used to conclude this fine a point. In regard to the days post PCI we know there is no difference in effect if cells are given day 5 vs. day 8 but there is no effect if given day 3 so one would need to know how the actual day of delivery is weighted in the cut they did (the day administered is very important to outcome). There is no good correlation between the number of mononuclear cells infused which is irrelevant and the number of CD 34 cells which are a constituent of the mononuclear cells and the cells that cause the effect. In addition further confounding this analysis is that the more mononuclear cells infused the more cells there are to get in the way of the CD34 cells. MRI has less variability than standard echo and what is important is not effect size (i.e. how much the LVEF goes up) it is the percentage of patients that do not have a drop in LVEF that matters. What matters is preservation of heart muscle function (preservation of heart muscle function was shown, and is the goal of NeoStem's Phase II study).

Nichols

Can you expand on the importance of the trial size and impact it has on being able to analyze subgroup data?

Dr. Pecora

It is more than adequate for the general effect assessment and conclusion that bone marrow derived cells administered after an AMI via the coronary artery preserve heart muscle function and prevent adverse remodeling

Nichols

From an investor's perspective, what do you feel is the single most important take away from this report?

Dr. Pecora

In regard to AMR-001, in our study we are administering a much greater number of CD34 cells than prior studies and not admixed with mononuclear cells. In our study we have limited entry to patients with persistent cardiac dysfunction (LVEF <48% on day 4), which would indicate that most of our patients fall into the <40% category in this analysis (because the LVEF is taken before day 4 in these studies and tends to improve by day 4). Thus if an effect is observed in most studies used for this meta analysis than our study should result in a similar effect at minimum and could be greater because we are giving a greater number of potent cells to a sicker population.

Final Thoughts

Now, hopefully Dr. Pecora's response made this study easier to follow/understand. Unfortunately, retail investors tend not to pay attention to reports such as this, and only show interest at the end of Phase III trials when a study either "met" or "did not meet" primary and secondary endpoints. However, reports such as this can give you, as an investor, a better idea of future success, or a lack thereof. Then, you aren't as likely to respond to the daily volatility that is created with such stocks, and will feel better about your investment.

Disclosure: I am long NBS. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article. (More...)

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Big Pharma Companies will meet at the Geriatric Safe Medicines Summit to discuss performing clinical trials in older people, 16-17 September, London

Main Category: Conferences
Article Date: 19 Aug 2013 - 8:00 PDT Current ratings for:
Big Pharma Companies will meet at the Geriatric Safe Medicines Summit to discuss performing clinical trials in older people, 16-17 September, London

Patients over the age of 65 are prescribed the majority of prescription drugs used in the UK but are significantly under-represented in clinical trials. Statistics show that although over 65's carry 60% of the disease burden they are only represented at a rate of 32% in phase I-III Clinical Trials. Why do clinical trial recruitment designs neglect this patient population? 

Challenges which include co-morbidities, polypharmacy drug-drug interactions, adherence formulation challenges are just some of the difficulties faced when performing clinical trials in this population, not to mention the problems of delivery.

SMi's inaugural Geriatrics Safe Medicines Summit, taking place on the 16th-17th of September 2013 in London, will look to tackle these issues and will address Benefit-risk in this patient population and how clinical trials could be better designed to facilitate the participation of the elderly in clinical trials.

According to Nina Lee Barnett, Consultant pharmacist, Northwick Park Hospital who is speaking on day one "I am really looking forward to participating in this meeting. It is great to see a programme which includes internationally renowned contributors from a wide variety of backgrounds, all delivering sessions which support safer use of medicines in older people. This meeting is an opportunity to foster collaboration on research projects which include older people and to break down barriers preventing studies in this age demographic."

Through a novel range of case studies attendees will discover new market gaps, market strategies and focus on EMA geriatric medicines strategy and how modelling and simulation along with new patient reporting systems support clinical trials in older people.

Keynote speakers include Solange Rohou, Director Regulatory Affairs, AstraZeneca who will be presenting on: What has been done since the revision of the ICH E7 guideline? The Companies' view and Barbro Westerholm, Member of Swedish Parliament, who will speak on: Patient perspectives on healthy ageing.

Event highlights include:

Discover the benefits of performing clinical trials in older people Identify the key challenges and considerations when conducting clinical trials in older people Address reasons for clinical trial retention difficulties Discuss how modelling and simulation along with new patient reporting systems support clinical trials in older people Explore new market gaps and discover new market strategy Focus on the EMA geriatric medicines strategy

For the full conference programme and further information please visit:? http://www.smi-online.co.uk/goto/geriatricsummit55.asp

Alternatively contact Jonathan Collins on +44 (0)20 7827 6734 or email: jcollins@smi-online.co.uk

Sponsorship opportunities are available for this event, please contact Alia Malick on +44(0) 20 7827 6168.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our conferences section for the latest news on this subject.

About SMi Group

Established since 1993, the SMi Group is a global event-production company that specializes in Business-to-Business Conferences, Workshops, Masterclasses and online Communities. We create and deliver events in the Defence, Security, Energy, Utilities, Finance and Pharmaceutical industries.

We pride ourselves on having access to the world’s most forward thinking opinion leaders and visionaries, allowing us to bring our communities together to Learn, Engage, Share and Network. We hold events in over 30 major cities throughout the world including London, Paris and Singapore and to date have welcomed over 200,000 participants from 80 countries. For more information, please visit http://www.smi-online.co.uk

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Ethical issues are often not addressed in national clinical practice guidelines for dementia

Main Category: Alzheimer's / Dementia
Article Date: 13 Aug 2013 - 14:00 PDT Current ratings for:
Ethical issues are often not addressed in national clinical practice guidelines for dementia

Twelve national dementia clinical practice guidelines included only half of 31 ethical issues the authors had identified as important in patient care, finds a study by Daniel Strech, of Hannover Medical School, Hannover, Germany, and colleagues, published in this week's issue of PLOS Medicine.

The authors identified current national clinical practice guidelines for dementia care published in English or German. They had previously systematically reviewed ethical issues in dementia care and they used thematic text analysis to assess whether and how the ethical issues were addressed in the guidelines. In the 12 national practice guidelines identified, an average of 49.5% of the 31 ethical issues were addressed (range, 22% to 77%). National guidelines differed substantially with respect to which ethical issues were represented, whether ethical recommendations were included, whether justifications or citations were provided to support recommendations, and to what extent the ethical issues were explained.

The clinical practice guidelines were published by a central governmental institution in 6 countries (Australia, France, Malaysia, New Zealand, Singapore, United Kingdom), by a medical association in 4 countries (Canada, Germany, Scotland, United States of America), one by a statutory health insurance body (Austria), and by an expert panel in one country (Switzerland). The authors state, "All guidelines explicitly acknowledged the involvement of experts from different specialties (most often from psychiatry, neurology, gerontology, and family medicine)."

Four (13%) ethical issues were not addressed in at least 11 out of 12 CPGs: "Adequate consideration of existing advance directives in medical decision making.", "Usage of GPS and other monitoring techniques ", "Covert medication" and "Dealing with suicidality."

The authors conclude, "Ethical issues and how to deal with them are important for guidelines to address, for the medical profession to understand how to approach care of patients with dementia, and for patients, their relatives, and the general public, all of whom might seek information and advice in national guidelines."

Furthermore, although clinical practice guidelines are "meant to improve standards of clinical competence and professionalism by referring explicitly to evidence-based information on benefits and harms", the authors state that clinical practice guideline development manuals worldwide fail to address how to include disease-specific ethical issues.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our alzheimer's / dementia section for the latest news on this subject.

This work has been funded by the German Research Foundation (DFG) through the research project Ethics Guide (STR 1070/2-1). The article processing charge was funded by means of the DFG-Project ‘‘Open Access Publishing’’ by the German Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Inclusion of Ethical Issues in Dementia Guidelines: A Thematic Text Analysis

PLoS Med 10(8): e1001498. doi:10.1371/journal.pmed.1001498

Knüppel H, Mertz M, Schmidhuber M, Neitzke G, Strech D (2013)

PLOS Medicine

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Low Risk Ankle Rule clinical trial

Main Category: Bones / Orthopedics
Also Included In: Radiology / Nuclear Medicine;  Pediatrics / Children's Health
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
Low Risk Ankle Rule clinical trial

Radiography is widely used in diagnosing ankle injuries, with 85%-95% in pediatric injuries, although only 12% of these show fractures.

"Radiography is unnecessary for most children's ankle injuries, and these high rates of radiography needlessly expose children to radiation and are a questionable use of resources," writes Dr. Kathy Boutis, a pediatric emergency department physician at the Hospital for Sick Children (SickKids) and the University of Toronto, with coauthors.

The Low Risk Ankle Rule is highly accurate at identifying fractures and can potentially reduce the need for radiography by 60%. It states that if a child with an ankle injury has a low-risk examination, ankle radiography may not be necessary to further exclude a high-risk ankle injury. If a subset of minor lateral ankle fractures is missed, evidence shows that these are exceptionally stable and low risk for any future issues and can be treated like an ankle sprain. Reducing radiography can lower exposure to low levels of radiation, contain costs and speed up treatment.

Researchers implemented the Low Risk Ankle Rule in 6 Canadian emergency departments to determine whether it reduced the use of radiography in children. The study involved 2151 patients (1055 at intervention and 1096 at control sites) between the ages of 3 and 16 years who presented at an emergency department with a nonpenetrating ankle injury. By applying the rule, the use of ankle radiography was reduced by about 22%. This reduction was consistent in different emergency departments and is similar to the Ottawa Ankle Rule used with adults.

"The implementation of the Low Risk Ankle Rule led to a significant decrease in imaging, associated increase in clinically important fractures being missed or decrease in patient or physician satisfaction," write the authors. "The ankle rule has potential broad applicability to emergency departments throughout most of the developed world, and widespread implementation of this rule could safely lead to reduction of unnecessary radiography in this radiosensitive population and a more efficient use of health care resources."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Effect of the Low Risk Ankle Rule on the frequency of radiography in children with ankle injuries

Kathy Boutis, Paul Grootendorst, Andrew Willan, Amy C. Plint, Paul Babyn, Robert J. Brison, Arun Sayal, Melissa Parker, Natalie Mamen, Suzanne Schuh, Jeremy Grimshaw, David Johnson, Unni Narayanan. CMAJ August 12, 2013 First published August 12, 2013, doi: 10.1503/cmaj.122050

Canadian Medical Association Journal

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Seeking a clinical test for breast cancer

Main Category: Breast Cancer
Also Included In: Pregnancy / Obstetrics
Article Date: 14 Aug 2013 - 1:00 PDT
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Seeking a clinical test for breast cancer

An international scientific collaborative led by the Harvard Stem Cell Institute's Kornelia Polyak, MD, PhD, has discovered why women who give birth in their early twenties are less likely to eventually develop breast cancer than women who don't, triggering a search for a way to confer this protective state on all women.

The researchers now are in the process of testing p27, a mammary gland progenitor marker, in the tissue of thousands of women collected over a 20-year period - women whose histories have been followed extremely closely - to see if it is an accurate breast cancer predictor in a large population of women. If the hypothesis is confirmed, likely within a few months, Polyak says the commercial development of a clinical test for breast cancer risk would follow.

In a paper just published in the journal Cell Stem Cell, the researchers describe how a full-term pregnancy in a woman's early twenties reduces the relative number and proliferative capacity of mammary gland progenitors - cells that have the ability to divide into milk-producing cells - making them less likely to acquire mutations that lead to cancer.

By comparing numerous breast tissue samples, the scientists found that women at high risk for breast cancer, such as those who inherit a mutated BRCA1 or BRCA2 gene, have higher-than-average numbers of mammary gland progenitors. In general, women who carried a child to full term had the lowest populations of mammary gland progenitors, even when compared to cancer-free women who had never been pregnant. In addition, in woman who gave birth relatively early, but later still developed breast cancer, the number of mammary gland progenitors were again observed to be higher than average.

"The reason we are excited about this research is that we can use a progenitor cell census to determine who's at particularly high risk for breast cancer," said Polyak, a Harvard Stem Cell Institute Principal Faculty member and Harvard Medical School professor at the Dana-Farber Cancer Institute. "We could use this strategy to decrease cancer risk because we know what regulates the proliferation of these cells and we could deplete them from the breast."

Research shows that two trends are contributing to an increase in the number of breast cancer diagnoses - a rise in obesity and the ever-increasing number of women postponing child bearing. The scientists' long-range goal is to develop a protective treatment that would mimic the protective effects of early child bearing.

The research, which took five years to complete, began with conversations between Polyak and John Hopkins University School of Medicine Professor Saraswati Sukumar, PhD. The two scientists formed collaborations with clinicians at cancer centers that see large numbers of high-risk women in order to obtain breast tissue samples. They also worked with genomics experts and bioinformaticians to analyze gene expression in different breast cell types. At times, Polyak and Sukumar had trouble convincing others to help with the study, which is unique in the breast cancer field for its focus on risk prediction and prevention.

"In general people who study cancer always want to focus on treating the cancer but in reality, preventing cancer can have the biggest impact on cancer-associated morbidity and mortality," Polyak said. "I think the mentality has to change because breast cancer affects so many women, and even though many of them are not dying of breast cancer, there's a significant personal and societal burden."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject.

Members of Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Beth-Israel Deaconess Medical Center, Harvard Medical School, Harvard School of Public Health, John Hopkins University School of Medicine, Coimbra University Hospital, Thomson Reuters Healthcare & Science, NICTA Victoria Research Laboratory, University of Melbourne, University of Oslo, Baker IDI Heart & Diabetes Institute, Baylor-Charles A. Sammons Cancer Center, St. Vincent’s Institute, USC Norris Comprehensive Cancer Center, UCSF Helen Diller Family Comprehensive Cancer Center, and Peter MacCallum Cancer Centre contributed to this research.

The main supporter of this research was the Avon Foundation, with additional contributions by the National Cancer Institute, the Susan G. Komen Foundation, the Terri Brodeur Foundation, the US Army Congressionally Directed Medical Research Program, the Victorian Breast Cancer Research Consortium, the St. Vincent’s Hospital Melbourne Research Endowment Fund, the Victorian Government’s OIS Program, the Programme for Advanced Medical Education, and the Cellex Foundation.

Harvard University

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Adaptimmune announces opening of Phase I/IIa clinical trial in ovarian cancer

Main Category: Clinical Trials / Drug Trials
Also Included In: Ovarian Cancer
Article Date: 29 Jul 2013 - 2:00 PDT Current ratings for:
Adaptimmune announces opening of Phase I/IIa clinical trial in ovarian cancer

Adaptimmune has announced that it has opened a Phase I/IIa, multiple-site, two-cohort, open-label clinical trial in ovarian cancer at Roswell Park Cancer Institute (RPCI) in Buffalo, N.Y., and City of Hope (COH) in Duarte, Calif.

Researchers will investigate the safety, bioactivity and effectiveness of treating patients with their own T cells after genetically engineering the cells to enhance their anti-tumor properties.

"T cells are the foot soldiers of the human immune system, attacking invaders like bacteria, viruses and cancer," says Kunle Odunsi, MD, PhD, Director of RPCI's Center for Immunotherapy and the study chair. "We believe that by modifying the T cells so that they express a high-affinity receptor for a protein that is a known cancer/testis (CT) antigen, we can fully exploit their ability as cancer killers."

During the trial, T cell receptors (TCRs) that have been developed using Adaptimmune's unique TCR enhancement technology will be deployed to target two CT antigens, NYESO-1 and LAGE-1. They will be transferred to the patients' T cells in a process for autologous T cell manufacturing developed by Carl June, MD, and Bruce Levine, PhD, at the Perelman School of Medicine at the University of Pennsylvania, Pa., and then licensed to Adaptimmune. Manufacturing will be performed centrally by Progenitor Cell Therapy in Allendale, N.J.

Adaptimmune is the regulatory sponsor, owns the core T cell receptor technology, and is funding the study. Dr. Odunsi is the lead clinical investigator at RPCI and protocol Chair. Mihaela Cristea, MD, associate clinical professor, Medical Oncology, is the lead clinical investigator at City of Hope.

The study is opening on the heels of promising clinical data emerging in sarcoma and myeloma studies, where the same engineered T cell product is under investigation. Interim data from these studies was presented at the American Association for Cancer Research Annual Meeting in March and American Society for Cell and Gene Therapy Annual Meeting in May of this year.

Ovarian carcinoma is the fourth-most-common cancer in women, accounting for approximately 22,000 new cases and 15,000 deaths per year in the United States. With standard therapy, long-term response rates are low, and the five-year survival rate for advanced ovarian cancer is only 30%. The clinical trial focuses on this unmet medical need and will include patients who are resistant to chemotherapy and/or have received more than two lines of chemotherapy for their ovarian cancer.

Infusion of the CT antigen-specific T cells will occur following a brief treatment with relatively high dose of "lymphodepleting" chemotherapy to prepare the patient's immune system for the gene-modified T cells. Previous clinical trials for different cancer indications have demonstrated that the lymphodepleting chemotherapy procedure is safe and promotes reconstitution of the immune system with the gene-modified T cells.

Dr. Odunsi is also the Chair of Gynecologic Oncology at RPCI and has been studying NY-ESO-1 vaccines in immunotherapy clinical trials for ovarian cancer patients since 2002. "NY-ESO is a very promising tumour antigen that I have worked with for years under the umbrella of the Cancer Vaccine Collaborative (CVC) Program of the Cancer Research Institute and the Ludwig Institute for Cancer Research," says Dr. Odunsi. "This technology basically allows us to genetically engineer a powerful T cell response in patients against the NY-ESO-1 antigen, which is very exciting."

Stephen J. Forman, MD, director of the T Cell Therapeutics Research Laboratory at City of Hope, initially brought the Adaptimmune technology to City of Hope due to his long-standing interest in adoptive and engineered T cell therapy for cancer. "The evaluation of this therapy in both hematologic and solid tumors will help us to understand the function of the engineered T cells in different tumor settings," says Dr. Forman, chair of the Department of Hematology & Hematopoietic Cell Transplantation and holder of the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. "I'm very enthusiastic to have this study join our programs at City of Hope, and to be able to offer our patients these novel and promising therapies."

A myeloma study using this technology is also planned at the site.

A total of six patients will be enrolled in the ovarian trial. Only patients capable of responding to the therapy - those with the correct tissue marker (HLA-A*0201) and whose tumor expresses NY-ESO-1 and/or Lage-1 - will be enrolled. Enrollment is expected to complete within six to nine months. If data are promising, the study may be extended to include more patients.

"We are enormously pleased to be working with world leaders in immunotherapy for cancer," says James Noble, CEO of Adaptimmune. "Ovarian cancer is an important clinical indication with which to evaluate our CT antigen specific TCRs because of the dismal prognosis of current standard care for advanced ovarian cancer, so the effects of the T cell immunotherapy can be rapidly assessed."

Additional study details and contact information for patients interested in finding out more about participation can be found at clincialtrials.gov, under trial identifier number NCT01567891.

Both City of Hope and Roswell Park Cancer Institute are National Cancer Institute-designated Comprehensive Cancer Centers.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our clinical trials / drug trials section for the latest news on this subject.

Clinical trial: Autologous T Cells Expressing Enhanced TCRs Specific for NYESO-1/LAGE in Patients With Ovarian Cancer

Dr. Kunle Odunsi, Dr. Cristea and Dr. Forman have no financial interest or other relationship with Adaptimmune Ltd, apart from their scientific collaboration in conducting laboratory experiments and planning human clinical trials.

Adaptimmune

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Fullest clinical report of Saudi MERS cases to date points to important differences with SARS

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Flu / Cold / SARS
Article Date: 26 Jul 2013 - 2:00 PDT Current ratings for:
Fullest clinical report of Saudi MERS cases to date points to important differences with SARS

Saudi and UK scientists provide the most detailed picture yet of the clinical and laboratory characteristics of Middle East Respiratory Syndrome (MERS) coronavirus, revealing a wide range of clinical symptoms and an extremely high death rate among patients with co-existing medical conditions.

The new research, published in The Lancet Infectious Diseases, also reveals some important differences with severe acute respiratory syndrome (SARS).

MERS emerged a year ago in Saudi Arabia and almost all those infected have been reported there, or have been linked to people who contracted the virus there.

The new analysis, the largest case series to date, includes 47 cases (46 adults, 1 child) of confirmed MERS infections from Saudi Arabia between Sept 1, 2012, and June 15, 2013.

By combining clinical records, laboratory results, and imaging findings with demographic data, the authors noted a trend of older patients, more men, and patients with underlying medical conditions who succumb to the disease.

As with SARS, MERS infections presented with a wide spectrum of symptoms. Most patients admitted to hospital exhibited fever (98%), chills/rigors (87%), cough (83%), shortness of breath (72%), and muscle pain (32%). A quarter of patients also experienced gastrointestinal symptoms, including diarrhoea and vomiting.

However, in contrast to SARS, the majority of cases (96%) occurred in people with underlying chronic medical conditions including diabetes (68%), high blood pressure (34%), chronic heart disease (28%), and chronic renal disease (49%).

"Despite sharing some clinical similarities with SARS (eg, fever, cough, incubation period), there are also some important differences such as the rapid progression to respiratory failure, up to 5 days earlier than SARS"*, explains Professor Ziad Memish, the Deputy Minister for Public Health from the Kingdom of Saudi Arabia, who led the research.

"In contrast to SARS, which was much more infectious especially in healthcare settings and affected the healthier and the younger age group, MERS appears to be more deadly with 60% of patients with co-existing chronic illnesses dying, compared with the 1-2% toll of SARS. Although this high mortality rate with MERS is probably spurious due to the fact that we are only picking up severe cases and missing a significant number of milder or asymptomatic cases, so far there is little to indicate that MERS will follow a similar path to SARS."*

According to co-author Professor Ali Zumla from University College London, "The recent identification of milder or asymptomatic cases of MERS in health care workers, children, and family members of contacts of MERS cases indicates that we are only reporting the tip of the iceberg of severe cases and there is a spectrum of milder clinical disease which requires urgent definition. Ultimately the key will be to identify the source of MERS infection, predisposing factors for susceptibility to infection, and the predictive factors for poor outcome. Meanwhile infection control measures within hospitals seem to work."*

Writing in a linked Comment, Professor Christian Drosten from the University of Bonn Medical Centre in Germany points to the urgent need for accurate diagnostic tests to help focus control efforts and minimise the risk of spread to others, "To ascertain relevant data for MERS epidemiology, we need to develop serological assays using samples from well defined groups of patients, such as described here. Population-based antibody testing could establish the extent of MERS-CoV infection, instead of only seeing the tip of the iceberg represented by cases admitted, such as those summarised in this important paper."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject.

*Quotes direct from authors and cannot be found in text of Article.

The Lancet

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Discussion roundup: Clinical commissioning groups

The debate explored whether GPs are able to balance their workloads with new managerial duties. Photograph: Martin Godwin for the Guardian

Mark Wilkinson, chief officer, NHS Barnsley CCG: "We have to look at how we can fully utilise the CSU. I'm challenging my team to explore CSU options rather than simply recreating our own in-house capacity."

Phil Mettam, chief officer, NHS Bassetlaw CCG: "We have developed a way of working where staff have supported autonomy, clinicians are predominantly involved in service conversations (not governance), and everyone is encouraged to be pragmatic and flexible."

Jonathan Sheffield, chief executive, the National Institute for Health Research Clinical Research Network: "In some parts of the country, barriers to research have really been broken down by the determination of CCG's to make sure excess treatment costs related to research are being covered. But in other areas, because the guidance has yet to be revised by the National Commissioning Board, there has been some rejection of requests for excess treatment costs. We also have some instances of new qualified providers being unsure, and even sometimes unwilling, to support research in their clinical area."

Mark Wilkinson: "I'm not sure the actual barriers have changed as a consequence of reconfiguration. What I suspect has happened, although this will be highly variable across the country, is that attention (at least in the transition from PCTs to CCGs) has been focused elsewhere on setup, building new relationships, bedding in new governance arrangements etc."

Chris Naylor, fellow, King's Fund: "I think there's a general spirit of wanting to support learning and sharing of best practice – the barrier, though, is time, which for most people working in CCGs over the last year has been in very short supply."

Jonathon Fagge, chief executive, NHS Norwich CCG: "Last year we commissioned Equal Lives to develop a co-production model for us. The first project will be community mental health services. Equal Lives will recruit and support a community involvement panel of service users and community representatives. We will jointly develop the service description, manage a wider public consultation, co-produce the service specification, and then involve the panel in bid evaluation."

Mark Wilkinson: "At Barnsley CCG we are determined to become an example for patient and public engagement. Quite how we move from aspiration to delivery requires quite a shift. And I do think this is an area where CCGs could do with some help."

Jonathan Sheffield: "The NIHR Mental Health Research Network team have strong links to patient groups and we involve patients in the design of questions to be answered through research, as well as specifically using patients to review protocols prior to implementation of studies."

Victoria Bleazard, associate director of policy, research and campaigns, Rethink Mental Illness: "We often hear of people being consulted by local authorities and different bits of the NHS at the same time on pretty much the same questions. Some models are being developed to try and join up engagement across agencies so that there are more resources to do it better and properly understand local need."

Phil Mettam: "We try and engage on a themed basis ... We hold an annual Big Health day where we invite people with a learning disability and their carers to tell us what they think about how the NHS, LA, and voluntary sector is supporting them and looking after them."

Robert McGough, partner in DAC Beachcroft's health commercial team: "There are a variety of approaches to member engagement as the governance structures have been set up in varying ways – some have more centralised structures with more control in the governing bodies, others delegate to localities to get local practice engagement."

Jonathon Fagge: "Provided CCGs focus on improvement rather than assurance I believe we can be a catalyst for improvement in the quality of primary care, and maintain good relationships with our members."

Chris Naylor: "One concern I've heard raised is about NHS England having limited capacity to perform performance management responsibilities. Some CCGs seem to be anxious that they will be sucked into that role in spite of their intentions to strike a supportive relationship with members."

Michael Scott, chair of the NHS Confederation's Community Health Services Forum: "Our early experience as a provider is that we find that there could be stronger links, ie what we are asked contractually to deliver by the CCG can be at odds with individual practice priorities and vice versa."

Chris Naylor: "The financial environment is obviously a big challenge. To that I'd add the challenge of engaging local GPs and demonstrating to them that CCGs can bring about improvements for GPs and their patients."

Robert McGough: "I would add the challenge of understanding their "inheritance" from the PCT – what the legacy contractual and structural issues are, what has actually transferred to the CCG, and what else may be delegated from NHS England, as well as how they engage with effective commissioning support services."

Richard Vautrey, deputy chair of the British Medical Association GP committee: "Many CCGs are still trying to get the right staff in place. All are faced with working out the right relationship between them and the new bodies working with them, particularly the area team of NHS England, local authorities and CSUs."

Jonathon Fagge: "Overall I feel very optimistic about how CCGs have coped with the challenges so far, and are geared for the future. The CCG leaders I meet are ambitious for their organisations, clinically engaged and patient-focused, and ambitious to create a legacy of genuine improvements in healthcare."

Jonathan Sheffield: "The introduction of CCG's offers a real opportunity for clinical involvement in the development and delivery of research. The opportunity to make ground breaking improvements in clinical healthcare is through research and any healthcare provider needs to have an approach to research that ensures that the best, most modern, treatments are made available to patients."

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How clinical commissioning groups are handling new responsibilities

CCGs are here to commission health services and work with patients and practices to ensure they understand local services and their quality. Photograph: Alamy

One hundred days have now passed since 1 April and the official birth of clinical commissioning groups (CCGs). As a GP and CCG chair it has been one of the most exciting, frustrating and meaningful periods of my career.

For most CCGs, delegated authority from primary care trust clusters, and therefore responsibility, had been in place for some time before April. However the process of authorisation and establishing organisations undoubtedly became a necessary distraction, with process and structure the focus.

Authorisation was essential to ensure we build robust, patient-focused organisations capable of fulfilling our statutory duties. CCGs were the only part of the new system to have been through this process, despite the number of new structures in the commissioning system. Since authorisation it has been good to get back to what we are here to do — commissioning health services and working with patients and practices to ensure we understand local services and their quality.

Bassetlaw CCG is a comparatively small CCG, with 12 practices and 112,000 patients in north Nottinghamshire. We have the same issues as many of our neighbours – high mortality and morbidity levels, areas of significant deprivation, obesity and substance misuse. We have a two-tier local authority system and we are members of Nottinghamshire health and wellbeing board. However, 90% of our patients use acute health services based in northern England – in South Yorkshire (including Bassetlaw hospital as part of Doncaster and Bassetlaw hospitals foundation trust).

Much of our time, therefore, is spent developing partnerships. Many of the commissioning organisations we work with are new, including NHS England, public health teams and the health and wellbeing board. Practices and providers are important as pre-existing parts of the system, and have been essential in understanding our local health services and outcomes. We have built transparent relationships with our providers, openly discussing services, capacity and performance. We meet neighbouring CCGs regularly to discuss commissioning on a regional level such as cardiology services and networks.

Quality assurance forms a significant part of our role. Performance indicators and targets are a key part of this, but we have also reviewed issues raised by member practices and patients. Service development has been one of our most important work streams. It is essential that we seek continuous improvement in services for patients, and not simply monitor what we already have. GPs work closely with managers to improve pathways and we have successfully commissioned new musculoskeletal, dermatology, cardiac rehabilitation and community paediatric pathways for local patients.

As a CCG we have a strong sense of responsibility for our local population. Patient engagement is central to this. We have well established practice patient groups and groups within the CCG, and this role is led by our new lay member who has worked hard to ensure we have a new, meaningful approach. We have developed a series of summits with patients, carers and providers including extremely successful dementia and learning disability events.

We have a number of commissioning priorities as a CCG. Some, such as developing integration of services and pathways, have been enhanced by the development of an integrated care board chaired by the local authority. Some have arisen due to performance issues, such as A&E performance. We have worked closely with practices, visit A&E weekly and have commissioned increased capacity within the department and acute medical services with significant results. Targets are now being met and we have services with better access to senior staff over seven days and diagnostics.

There are significant challenges. Being allowed access to patient information is essential if we are to improve outcomes and commission effectively. Running cost, set at £25 per patient, is a blunt tool that does not take into account organisational size and fixed costs, or local health needs. CCGs, particularly those such as Bassetlaw, who have natural communities but are relatively small, are extremely lean organisations where clinical and managerial time is limited and we have learned to work as an efficient, effective team. It is essential that this is valued when we have assurance meetings and that reporting upwards does not distract us from our role.

We operate as just one part of a complex commissioning system. We need to ensure we are active partners alongside public health, regulators and NHS England, and that our clinical involvement and patient engagement lead to better outcomes.

After 100 days I'm optimistic. Clinical commissioning is delivering. The NHS needs it to succeed.

Dr Steve Kell is chair of Bassetlaw CCG and co-chair of NHS Clinical Commissioners Leadership Group

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Clinical Research A Second Career for Health and Science Professionals

Who will you reasonably anticipate finding signed up for clinical research courses? Whether in Toronto or Tokyo, japan, wherever you're, the reply is prone to incorporate a number of scholars who originate from health or sciences.

Actually, one recent paid survey recognized "clinical research connect" being an ideal second career for individuals 50 and also over. How can this be this kind of attractive career option for individuals this age group? You will find a lot of reasons.

1. Highly developed feeling of responsibility

The graduates of clinical research training safeguard the security in our food and drug supply. They have to blend legal understanding with laboratory know-how good recording abilities with higher business abilities. In some instances, they might be responsible for a whole team. They might be exposed for an audit. They have to have the ability to contact co-workers, clients and government authorities. They require the motivation to remain current on developments within their area.

2. Among the marketplaces for clinical research training is companies

A good reason that clinical research courses abound is the fact that there's a requirement on their behalf, which demand originates from companies who would like well-trained employees. By signing up their employees in related programs, companies make sure that employees have sufficient learning such clinical cornerstones as:

- pharmacology

- biopharmaceuticals

- medical products

- biotech

- pathology

- anatomy

- physiology

- calculating costs

- allocating assets

- development methods

- guidelines

- developing items

So, if you're already utilized by a pharmaceutical firm or food producer, you might want to make use of the connections that you have to segue right into a second career within the laboratory.

3. Competitive salary

Like a experienced professional, a clinical research connect can get to create a good earnings, around $80,000 annually, by a few estimations. This really is great news at any stage of existence, but even more in order the retirement years draw closer, when you wish to make certain you have enough money to last before the finish of the existence.

4. Interest in affiliates

Should you lookup jobs for graduates of on job boards, everyone will likely show exactly the same factor: posts in abundance. Obviously the amount of posts which come in searching is dependent available on the market (both generally and in your area) however it may be beneficial to start looking when for brand new openings.

Intrigued? If you're already employed, discover in case your employer offers any re-training programs. Otherwise, look in your area for clinical research courses. Most major metropolitan areas should offer them. Have fun with starting your next career!

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