Pharma Strategy Blog

FDA, social media and patients

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Last month, the FDA held open hearings to debate the topic of social media guidelines for the pharma and biotech industry.  I was following from afar on my iPhone at the NY Chemotherapy meeting, as this was the first such hearing since 1996 and many in the industry were excited that the FDA at ,east appeared to be listening and finally getting social media. 

Several things struck me at once while following the Twitter stream on Fabio Gratton's excellent custom site for the purpose, FDAsm.com:

1. There were a lot of agency people presenting (some argued they had a vested self interest)
2. Not many pharma people were actually presenting (despite griping about the lack of guidelines in this space)
3. Not many patients or patient advocacy groups were involved either.

What was also interesting was that there was plenty of justification for the use of social media, but very little in the way of practical solutions and suggestions that the FDA could consider, thus speeding up the process.

In the past, the FDA have claimed that it is all about the message not the medium, witness sending 14 pharma and biotech companies letters back in April this year for their Google ads with 1 or 2 clicks from the full safety information.  However well intentioned the wrist slap was, it ws later shown to negatively affect public health, as some of the presenters at the meeting clearly showed. 

Rather than look at this incident negatively, I wondered if the respectful and interesting interactions between the FDA DDMAC and industry seen at the hearings could not continue in the same vein on a more frequent basis.  Dialogue and discussion make for much more constructive rather than destructive relationships.

There are several things I'd like to point out about safety and adverse events (AE's):

• They happen, no drug is immune from them, so best not to avoid them
• Have policies and procedures for easily recording and submitting AE's
• The currernt MedWatch reporting system is awful and cumbersome to use
• If there was a better system, more doctors and patients would be more likely to report them
• Social media could be a great tool for improving the MedWatch system, reaching more people, more easily and collating the relevant information

What was particularly poignant about these hearings is that, for me at least, a great chance was missed to put patients front and centre, whether this was in the form of better public health information and education or looking at ways to improve clinical outcomes.

Are patients really out of sight and out of mind?

The FDA will still be collecting comments and suggestions until February 2010, so if you missed the hearings this month, please do take the time and contribute offline.  The link to the FDA is here type in FDA-2009-N-0441 in the search box and it will bring up the dockets for comments.

In the meantime, John Mack of Pharma Marketing News is also running an anonymised survey to gather feedback and further suggestions post meeting and will send the aggregated results to the FDA.  Click here to make your views known!

Things to be thankful for

The day before Thanksgiving, I spent a delightful afternoon here in San Diego with Mary Canady of Conprendia (@comprendia on Twitter). She runs a company specialising in Biotechnology Marketing. The beauty of meeting people like Mary on Twitter is the opportunity the platform offers for impromptu tweetups as you travel the world or even in your local area. Go check her out, she had some cool stuff for bootstrapping your marketing if you're a small company on a tight budget.

While walking around the park, we came across the botany pavillion. I love these little treasures, there's always some stunning flora and fauna to photograph, as the picture in this post shows.

Sometimes, we need to remember that for all the noise we make about healthcare and drug development (in any therapy area), it is ultimately the simple things that matter... a shared experience, a photo, an understanding. Listening goes a long way. Yesterday, while visiting the family of @MrGunn for a truly sumptuous Thanksgiving spread, I received a text message from a client. Not work related, but a short message wishing me a happy Thanksgiving. Very touching.

Years ago, when I was a child stuck in a shockingly grey bleak hospital awaiting surgery to remove a tumour, a dear friends Mum waltzed in and presented me with a huge bright purple flower in a pot. It was truly stunning and that simple gesture brightened up the place for everyone no end.

So this Thanksgiving the purple flowers in the botanical garden reminded me to be thankful to be alive 30 years on.

What are you thankful for?

Commentary on the breast cancer controversy

After the recent furore over the breast cancer guidelines, I've been ignoring the hype and hysteria in the news and quietly waiting for some thoughtful commentary from some breast cancer experts I respect.

This morning I got my wish with an email alert from the New England Journal of Medicine. In it, two well respected breast cancer physicians from rhe Dana Farber Cancer Insitute have summarised their views in an editorial. You can read the whole commentary for free here:

http://content.nejm.org/cgi/content/full/NEJMp0911288?query=TOC

One point in particular struck me. The guidelines apply to those who are low risk, implying those women who are high risk (family history of breast or ovarian cancer, BRCA1 or BRCA2 positive etc), should still continue as before.

Their sensible and well thought out article is worth reading carefully and sharing with others.

A lot of people gave asked me what I'm going to do or would advise as one of those forty something women.

Well, I have a baseline and have been adjudged to be high risk so providing my insurance carrier is agreeable, I'll be continuing with annual mammograms at NY Weill Cornell imaging center. This last point is important. My own experience of mammograms in suburbia was less than satisfactory and I would absolutely advocate going to get any tests at a cancer center where they have the latest technology and the best teschnicians, radiographers and pathologists. It does make a difference, possibly even between an accurate result and a false positive or negative.

Once you reach 40, politely insist on a baseline at your annual physical and get tested for BRCA1 and 2, after all that distinct aunt wasn't aware in time and you don't want to make the same mistake. These mutations drive aggressive breast and ovarian cancers. The most important thing is to get a baseline done, that gives you a comparion from which any changes can be detected early.

Check out the article and let me know what you think in the comments below.

Hitting the blind side

This week I've been reading a fascinating book about Michael Oher's journey to the NFL. The title?

The Blind Side.

And then I had a thought. That's exactly what the cancer cell aims to protect it's blind side from assault.

New developments in cancer (and peobably other therapy) treatments will come when scientists think strategically about attacking the vulnerabilities that either negate that protection or find new create ways to kill the menace.

Chemotherapy was used as blunt tool in the same way Lawrence Taylor was a one man sacking machine for the Giants. As offences evolved, smart defensive teams switched from a 4-3 to a 3-4 and had large, agile and athletic ends rush the passer. Strategy in football is constantly evolving on offence and defence.

What do we need now?

Maybe some creative and subtle gadget plays, such as nanotechnology approaches mentioned in the post on pancreatic cancer.

Or perhaps just thinking strategically out of the box as Gail Roboz did when she asked at the Chemotherapy Foundation, "why can't we keep more people in remission?"

There are many other interesting examples evolving and being tested in company pipelines right now, as the Novartis-Incyte deal shows.

I'll be interested in reporting what new at ASH next week: watch this space for more details!

New developments in pancreatic cancer @AACR

Pancreatic cancer is a devastating disease with a generally poor prognosis, largely because it is usually detected in late stage disease where chemotherapy options generally have a limited effect.  Typically response rates with gemcitabine are around 5%, with advanced patients living around 5-6 months on average.  Erlotinib, an EGFR inhibitor, is also approved in the USA for treatment of the disease, but the therapy only adds approximately two weeks to survival.  Many doublets and triplets have been tried and tested over the last 10 years, with little impact on survival.  It was, therefore, exciting to see some young researchers presenting interesting and novel strategies at AACR this week to try and evade the resistance inherent in the disease.

Recently, Nab-paclitaxel (abraxane) has been granted orphan drug status in pancreatic and melanoma cancers.  The rationale for using Nab-paclitaxel in pancreatic cancer is that it appears to weaken the stroma surrounding the tumour and also synergistically increases the effect of gemcitabine, the standard of care for the treatment of late stage disease when surgery is not an option. 

Anirban Maitra presented a poster which showed how Abraxane targets the tumour stroma, depleting it, thereby reducing the impediment to chemotherapy.  The Nab-paclitaxel works by utilising endogenous albumin pathways via binding of the albumin to secreted proetin acid rich in cysteine or SPARC.  Interestingly, pancreatic cancer is known to overexpress SPARC and therefore offers a target for the drug.

In a Phase I/II trial presented earlier this year at ASCO by Daniel van Hoff, the median PFS with the combination was 6.9 months, and median OS was 10.3 months.  To put this in context, gemcitabine alone usually gives an OS of around 5 months, so adding Abraxane doubled the overall survival, which is a lot in pancreatic cancer.  Dr Maitra's research showed that this doubling of response occurred because there was a 3.5 fold increase in the amount of gemcitabine delivered in the tumour after the depletion of the stromal layer by Nab-paclitaxel.

This research therefore offers a fascinating insight into how other treatments could also be used in combination with Abraxane to potentially improve overall survival in this disease.

Two of the other interesting ideas came from a research group at the Massachusetts General Hospital here in Boston.  The first one, presented by Tayyaba Hassan, took an out of box approach to rethink how to get a drug that has shown some modest efficacy in pancreatic cancer, bevacizumab, inside the cell.  The drug is a VEGF inhibitor that typically acts on VEGF outside or on the ligand on the cell surface.  It has limited efficacy in mopping up the VEGF this way, because getting past the stromal layer, as Dr Maira showed, severely limits drug access. 

Hassan and her group decided to find a way to get the drug inside the cell to see if that would mop up more VEGF and induce a more durable response.  They created a nanotechnology based delivery device to simultaneously deliver the bevacizumab and an FDA approved light activated chemical in the tumour cells in a mouse model.  Photodynamic therapy (PDT) has been shown previously to improve treatment outcomes in pancreatic cancer.  However, in clinical trials where standard chemotherapy was combined with bevacizumab, there was no benefit in survival.  The theory was that perhaps not enough chemotherapy or monoclonal antibody therapy was getting through to mop up the VEGF and induce apoptosis in the pancreatic cells.

The results were highly interesting.

In the mice models, the nanotechnology device (nanocell) successfully delivered bevacizumab to the tumour cells and improved the acute response in the mice compared with those treated with bevacizumab alone.  The combination with PDT was associated with even greater improvements.

The nanocell also delivered enough bevacizumab to cause a 2 fold reduction in metastasis to the lungs, liver and lymph nodes.

Phase I trials are due to begin in humans and the results will be eagerly awaited.  If successful, the nanotechnology concept will offer a new and creative paradigm for delivering cancer drugs to the right place at the right time with greater effectiveness and less toxicity.

Prakash Rai and his colleagues at the MGH also looked at the possibilities with nanotechnology by combining it with photodynamic therapy (PDT) to simultaneously target the EGFR and MET pathway using cetuximab and PHA-665752:

Source: Zheng, Rai and Hasan, AACR Molecular Targets and Cancer Therapeutics Meeting, 2009 #A127

The goal behind the approach was to reduce cross-talk and escape routes for the cancer cell, attacking several pathways at once is one way to do this.  The end result is drug delivered more effectively inside the tumour cell and ultimately, a reduction in the tumour burden.  It will interesting to see if there is a reduction in metastasis and overall survival.

This novel approach could potentially be applied to other drug combinations and tumour types and offers a new targeted method of getting larger amounts of drug inside the cancer cell, where it can do more damage.

Why can't we keep AML patients in remission?

That was the key question posed by Gail Roboz during her improvised talk at the recent Greenspan Chemotherapy Foundation meeting in New York.  She was standing in for Janice Gabrilove who was unfortunately sick, but managed to put together 16 mins of incredible thoughts for where things could head next in the near future with this disease. 

The ideas Dr Roboz expressed gave me a lot of food for thought, so I thought I would try and summarise a brief synopsis.  If you want to hear the presentation and see the slides yourself, I would highly recommend checking out the Chemotherapy Foundation website in the link above.

If we take a look at the response rates in younger AML patients, we see some very high complete responses (CR) or remissions in the 70-80% range, yet 5 year survival is only in the 30% range:

A similar trend exists in the elderly AML group, although the corresponding numbers are a dispiriting 40-50% and 10-20% for complete response and 5 year overall survival respectively.

The answer, according to Dr Roboz, lies in understanding the role of the leukemia stem cells, which are largely quiescent and not killed by conventional chemotherapy.  They persist after treatment and probably most likely to be responsible for or involved in relapse.

Currently, there are no standard post remission therapies in AML.  Options include chemotherapy consolidation and allogeneic stem cell transplantation (SCT).  However, what is surprising is that minimal residual disease (MRD) evaluation and maintenance strategies showing a survival benefit are standard in ALL, but not AML. 

Given the poor results seen with maintenance chemotherapy in AML, Dr Roboz suggested it was time for a change in approach.  She noted that many targeted drugs with good science but do not work alone in active AML could be considered for maintenance therapies in CR, via clinical trials to determine their effectiveness.  These agents include the following:

In conclusion, her recommendations to try new ideas and novel approaches to the treatment of AML looks at ways of keeping the patients who achieve a complete response in remission for longer, thereby impacting the overall survival.  The suggestions for personalised treatment of AML included the following:

Given that this was an impromptu presentation at very short notice, it was very well thought through and delivered.  In fact, I would go so far as to say it was the one presentation that had the most vivid impact on me from the meeting, and there were many good ones over the course of four days.

Sometimes, we learn more and perhaps can see a better vision or approach when when someone articulates the issues and focuses on some new areas for consideration.  I wish more researchers thought strategically like this!

I'm looking forward to seeing some Pharma companies consider the idea of targeted therapies taken as maintenance therapies in patient with AML who have achieved complete remission.  If we can impact the 5 year survival rate for the better, that would be a wonderful thing indeed.

links for 2009-11-20

• FDA Warns of Unapproved and Illegal H1N1 Drug Products Purchased Over the Internet
  The U.S. Food and Drug Administration today warned consumers to use extreme care when purchasing any products over the Internet that claim to diagnose, prevent, treat or cure the H1N1 influenza virus. The warning comes after the FDA recently purchased and analyzed several products represented online as Tamiflu (oseltamivir), which may pose risks to patients.
  (tags: FDA H1N1 virus fake products)
• Possible origins of pancreatic cancer revealed
  MIT cancer biologists have identified a subpopulation of cells that can give rise to pancreatic cancer. They also found that tumors can form in other, more mature pancreatic cell types, but only when they are injured or inflamed, suggesting that pancreatic cancer can arise from different types of cells depending on the circumstances.
  (tags: pancreatic cancer inflammation origins KRAS surgery)

Buzzword bingo at AACR

After typing a short, but thoughtful, piece into the Typepad mobile app on the iPhone, it crashed into the cyber ether before I could send or save it.  Arrrgh!

It's always difficult restarting and retracing steps from scratch because the whole point of the mobile app is that it allows you to capture those sudden brainwaves and quick thoughts so easily.  Maybe next time I'll stick to audio and posting it via Posterous instead.  This made me realise that what we really need is a service that does a transcript of audio for say, a report or blog post, and allows editing before posting.  Boy, would that make my life so much easier! 

Image via CrunchBase

Maybe such an app already exists on the iPhone for capturing 10-15 mins of dictation, but the ones I've tried to date either rely on shorter timescales (Jott and ReQall) or can record 5-10mins, but offer no transcript (AudioBoo, iPhone Voice Memos).  This is something that would be really useful business-wise too.

If you know of something suitable for iPhone transcription, do send me a DM on Twitter (to @MaverickNY) or post a comment below.

Anyway </rant>, the purpose of today's post was originally to look at the topline trends and strategies emerging in oncology research based on 'buzzword bingo' that fun game we all play to lighten the mood while still keeping the essence of something.

Here are some buzzwords that cropped up time and time again this week in Boston at the AACR molecular targets in cancer therapeutics meeting based on almost 60 pages of tightly written notes (or spidery chicken scratch if you prefer):

• Heterogeneous
• Predictive biomarkers
• Prognostic biomarkers
• Molecular vulnerability
• Adaptive resistance
• Anything on PI3K/AKT/MEK/mTOR/RAS/RAS (double points)
• Escape route for cancer cell (triple points)

However, my favourite and probably most used phrase of the meeting was:

• Synthetic Lethality

Turns out that the term is not new, having been first described by Dobzhansky in 1946.  It essentially describes the situation whereby:

"A genetic interaction where the combination of mutations in two or more genes leads to cell death. The implications of synthetic lethal screens have been discussed in the context of drug development as synthetic lethal pairs could be used to selectively kill cancer cells, but leave normal cells relatively unharmed."

Source: Le Meur and Gentleman, 2008

In other words, either gene alone may not have much effect, but both together lead to apoptosis.

One of the most most prominent drug classes associated with synthetic lethality this week was the PARP inhibitors, particularly olaparib, an exciting new agent from KuDos/AstraZeneca that targets BRCA1 and BRCA2 mutations seen in breast and ovarian cancer. 

During one of the poster sessions, I spoke with KuDos' Chief Scientist, Mark O'Connor, who explained the concept of synthetic lethality even more simply.  He suggested thinking of the cancer cell as a table with 4 legs and then suddenly removing one leg (the two gene effect).  The result would be a rather unstable situation with a peculiar vulnerability.  I rather liked that visual metaphor.

Do check out the Pharma Strategy blog over the next few days for updated posts and commentary from AACR around new themes and research on prostate, lung, breast and ovarian cancers.

Related articles by Zemanta

• What's new at AACR on molecular targeting and biomarkers? (pharmastrategyblog.com)
• New drug 'can treat more cancers' (news.bbc.co.uk)

links for 2009-11-18

• Finding Breast Cancer Early: Age 40, Every Year
  We do believe that we should aim to choose 100% of the benefit. We should not forget that the “benefit” in this situation is reducing deaths from breast cancer. A 30% reduction in saving lives is not acceptable. We also recognize that mammograms are not perfect. We realize that women do have to get additional studies for suspicious lesions. We realize that some women have biopsies that do not show breast cancer. We realize that our predictive tests are not perfect, so that we can’t say with certainty which breast cancers are aggressive and require intensive treatment and which would—if left alone—never cause a problem. We realize that we need better screening tools, and that we must work diligently to improve the quality of screening mammography across the country. Until we have something better, what we have to work with to detect breast cancer early is the screening mammogram. Is it imperfect? Yes. Has it saved lives and reduced deaths from breast cancer? Absolutely.
  (tags: breast cancer screening mammography research statistics politics)
• The role of PI3K/PTEN/AKT/mTOR genetic variation in clinical outcomes following chemoradiotherapy for esophageal cancer - The American Journal of Hematology / Oncology (AJHO)
  Key research findings: ● Genetic variation in the core components of the PI3K/ PTEN/AKT/mTOR signaling pathway influences recurrence risk, overall survival, and response to chemoradiotherapy for esophageal cancer patients ● A cumulative effect and higher-order interactions among single nucleotide polymorphisms (SNPs) associated with recurrence risk were identified ● A single SNP in AKT2 — rs892119 — was associated with a poor clinical outcome based on all 3 endpoints
  (tags: PI3K PTEN AKT mtor esophageal cancer)
• Committee Leaders Call for GAO Analysis of Recent Prescription Drug Price Increases
  Leaders of the House Ways and Means and Energy and Commerce Committees sent a letter to the Government Accountability Office (GAO) last night requesting an expedited report on recent trends in prescription drug pricing.
  (tags: Politics pharmaceuticals drugs prices economics)
• "Mammograms and politics: Task force stirs up a tempest: Research, recommendations for breast cancer screening have long been debated"
  Ned Calonge, who chairs the 16-member panel, defended the recommendations and denied that cost or the debate over health-care reform played any role in the decision. "Cost just isn't a consideration when the task force deliberates," said Calonge, who is also the chief medical officer for the Colorado Department of Public Health and Environment. Twelve of the task force members were seated during the Bush administration, and the remaining four were chosen before President George W. Bush left office, he said.
  (tags: breast cancer screening mammography)
• Modeling Different Breast Cancer Screening Strategies
  new study which uses modeling to summarize the benefits and harms of breast cancer screening finds that regular mammography screening for women ages 50 to 74 reduces the risk of dying due to breast cancer, with a smaller benefit for women 40 to 49.
  (tags: breast cancer screening mammography)
• Breast Center Imaging and Administrative Directors Voice Opinion on Mammography Recommendations
  National statistics show that about 18 percent of all breast cancers occur in women aged 40-49, and, at Johns Hopkins, more than one in four breast cancer patients are among this age group. We also know that breast cancers occurring in women under 50 tend to grow faster and more aggressively than in older women and arise in denser tissues, making their early detection more difficult.
  (tags: breast cancer screening mammography)
• Screening for Breast Cancer
  The U.S. Preventive Services Task Force (USPSTF) recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older. Grade: B Recommendation.
  (tags: breast cancer screening mammography)
• Controversy Over Mammograms Echoes Earlier Dispute
  Way back in 1997, a committee of a dozen experts convened by the National Institutes of Health heard testimony, reviewed the scientific literature and mulled what to tell doctors and women in their 40s about screening for breast cancer.

  After weighing the risks and benefits, they concluded:
  [T]he data currently available do not warrant a universal recommendation for mammography for all women in their forties. Each woman should decide for herself whether to undergo mammography.

  
  
  (tags: breast cancer screening mammography)
  
  

What's new at AACR on molecular targeting and biomarkers?

At the AACR molecular targeting meeting in Boston, several key presentations have focused on lessons learned from previous kinase studies and using them to help guide future developments.

Charles Sawyers from MSKCC put together a particularly nice presentation looking at the lessons learned from CML and prostate cancer.  He noted that 75% of CML patients respond to imatinib and attain a complete cytogenetic response, with only a small number, 20% relapsing by 5 years. The question is why and what can be done to change this? 

Firstly, the natural course of the disease predicates that mutations will occur as the cancer finds ways to re-activate BCR-ABL in order for the leukemic cells to survive.  New kinase therapies in development now target not only BCR-ABL, but also the other mutations that evolve with time.  Both dasatinib and nilotinib not only have different conformations than imatinib, but also inhibit most of the other mutations that have been recognised to date.  However, neither targets the T315i mutation, but fortunately other compounds in R&D including AP24534, omacetaxine and others do.

Neil Shah from UCLA also made similar points in his talk and emphasised that as more therapies become available for the treatment of CML, so the ability to personalise therapy for each patient based on their particular mutation analysis now exists by choosing a kinase that is sensitive to the mutations arising. This is especially so in CML with a growing number of drugs available either commercially or through clinical trials.  This is great news for patients, because this cancer was once a death sentence but is now a chronic treatable disease that can be kept under control with targeted therapies.

Hilary Calvert from University College London discussed PARP inhibitors, which target the BRCA1 and BRCA2 mutations and also potentiate the effect of some chemotherapy drugs in vivo such as temozolomide.  He covered a number of these interesting agents in development, including olaparib and AG014699, and how tumour shrinkage occurs but drug resistance ultimately ensues due to intragenic deletion activity of BRCA2.  Despite platinum resistance developing in ovarian cancer, however, responses to olaparib have still been seen, so much work still needs to be done in this area to figure out what resistance mechanisms are in play and what strategies can be used to overcome them.  BRCA1 and BRCA2 mutations occur in both breast and ovarian cancers, so these cancers have been the primary targets for the PARP class of drug initially and represent an interesting new approach.

Kapil Bhalla from the Georgia Cancer Center described a novel new approach in breast cancer that made me stop and think.  The cancer cell is always looking for ways to survive and find alternative escape routes to achieve this despite chemotherapeutic drugs targeting it's death through apoptosis. They forced the cancer cell in the mammary fat pad of mice into autophagy, and then pulled the rug away by adding an autophagy inhibitor.  This was achieved by targeting heat shock response protein with panobinostat combined with an autophagy inhibitor, thus allowing apoptosis to continue instead of being inhibited. 

In this novel approach, Dr Bhalla described it succintly as,

"The panobinostat accentuates stress, causes autophagy and sets up the cell to be eliminated by autophagy inhibitors."

It will be interesting to see how this approach translates into humans and if it works, we may see more autophagy inhibitors developed that are tumour specific.

AACR have launched a series of podcasts from the meeting, including one with Charles Sawyers, which you can find here and download to listen to on your MP3 player or computer.  They make for very interesting listening, especially if you were unable to attend the meeting in person.

The increasing use of social media to recruit patients for clinical trials

In an effort to speed up the time to market, companies have always wanted to recruit clinical trials faster.  Traditional media was the starting point e.g. sending trial information to advocacy groups, advertising on television, radio, posters, bill-boards etc.  Now companies are increasingly looking at how social media can channel patients into clinical trials.  This is an exciting area that is outside of the reach of the current FDA debate on how social media is used for drug promotion.

Various models are now slowly emerging:

1.  Communities of people with similar diseases

Clinical trial information is being provided to websites that engage participants in a disease or therapeutic area. An example of this model is Patients like Me.

Patients like me is an interesting website that allows patients in several therapeutic areas including ALS,  Epilepsy, Fibromyalgia, Chronic Fatigue Syndrome, HIV, MS and Parkinson’s to share information about their treatment and learn from others.  Companies can arrange for emails to be sent to potential subjects with information about ongoing clinical trials in order to generate awareness.  The success of such sites is limited by the number of patients that sign up and the benefits the site offers.

2. Applications that enhance search ability

Web 2.0 applications are emerging that allow patients who are interested in clinical trials to find relevant information.  One useful application using this approach is TrialX, which allows users to search for trials based on the personal health information they store in your Google Health or Microsoft Health Vault account.  The limitation of this is it requires the user to initiate the search, so doesn’t raise awareness of a particular trial and of course, not everyone will be using an iPhone, particularly Moms who tend to be doing most of the health research in a family.

An interesting new website funded by the NIH, and set up by medical researchers at Vanderbilt is Research Match.  The site aims to create a searchable database of those interested in participating as a volunteer in research studies, not just clinical trials.  The site will be used by a consortium of research institutions that obtain NIH funding.  It will be interesting to see how many people sign up for this.

Previously on this blog, we have covered interesting clinical trial health apps available on the iPhone such as Clinicaltrials.gov from the NIH and Healogica, to name two.

3. Use of social media networking sites such as Twitter & Facebook

Major cancer hospitals such as M.D. Anderson, Roswell Park and the Mayo Clinic are leading the way in social media and all have a Twitter account, as do a few contract research organizations running clinical trials on behalf of Pharma companies such as Quintiles, Oncology CRO and others.  Some are just noisy broadcast mediums such as Quintiles with little interaction, whereas others have a professional social media manager such as Lee Aase of the Mayo Clinic, who does an excellent job with communications and patient interaction.  They even have Mayo Radio, and patients can tweet their questions using the hashtag #mayoradio. 

Roswell Park have a nice Facebook page as do MD Anderson, which also embedded their YouTube channel with interviews with leading physicians about clinical trial data and there are many others like this that are springing up.  If you are a cancer patient, then listening to leading national experts such as Dr Maurie Markman talk about ovarian cancer trial results can be very reassuring in this age of the empowered patient.

To date there is relatively limited use of these tools to generate awareness for specific clinical trials, a point also mentioned by an MD Anderson cancer center physician, Dr Anas Younes, on his lymphoma blog. His oncology colleague, Dr Naoto Ueno is also on Twitter and both interact regularly with their followers, and I have found them both to be engaging and helpful, as is Dr Jack West, an oncologist in Seattle, who runs the Grace cancer website site and blogs regularly on clinical trial data and analyses the results in a way that is most helpful for patients and caregivers alike.  It is clear from following them on social media sites that they are all very committed to improved medical education and patient outcomes.

One reason for the relatively limited uptake of social media tools in the hospital setting in general could be that the users of Twitter are not the target audience or the hospital communication staff are not particularly social media savvy.  It is, after all, still a relatively new medium with a seemingly bewildering array of tools at the disposal.  However, many caregivers, friends or family are likely to be using social media in some shape or form, so this should not be a reason for not generating trial awareness.  It would be interesting to do a social media monitoring study to look at clinical trial recruitment and it's overall effectiveness.

One of the other interesting developments is St. Judes Childrens Research Hospital who even have a page dedicated to their social media toolkit, which you can find here.

Other places where you can find out infomation about drugs in development and clinical trials include some really well organised patient groups.  One of my favourites is the Life Raft Group, which supports patients with Gastro-intestinal stromal tumours, a form of soft tissue sarcoma.  They have a website, which includes information on clinical trials, a MySpace page, and a Facebook page, while the GIST support group has a well stocked wiki that is a valuable resource for patients with this condition and also includes a nicely curated section on clinical trials and specialist physicians.

In conclusion, my thoughts are that the use of social media for clinical trial recruitment and patient engagement between patients, with health care professionals and ultimately the Pharma industry will continue to evolve, they have certainly come a long way from the 1990's when bulletin boards and online Yahoo patient forums were just beginning.

Does the clinical benefit of a drug justify it's cost?

The Obama administration provided $1.1 billion for health care comparative effectiveness research in the American Recovery and Reinvestment Act (ARRA).  Following this, the Institute of Medicine (IOM) delivered a report in June with comparative effectiveness research priorities (downloadable file).  However, it remains to be seen how comparative effectiveness will work in the U.S. to control costs and guide payers and providers on the cost/benefit of treatment options. 

There is little being said about comparative effectiveness in the debate on health care reform, which seems to be driven more by emotional sentiments such as these from Senator Baucus:

"There is no denying that our system is broken.  Millions of Americans struggle each day because they do not have the coverage they need. Currently, more than 46 million people are uninsured and therefore risk their health and financial stability every time they get sick."

U.S. physicians currently have little incentive to weigh the cost/benefits of drug, which is why direct to consumer advertising works.  Consumers see a drug advertised on television, resonate with the symptoms being described and go to their doctor who may prescribe it (if appropriate), often with little thought towards weighing the cost against the benefits provided.  That is because unlike the UK model, payment for the drug is up to the patient, and they either pay themselves or have it covered by the pharmacy benefit associated with their health care insurance.  There is little or no direct connection between the prescriber and the payer.

A recent editorial in the New England Journal of Medicine by Schwartz and Woloshin, argues that what is needed is for more of the information that already exists about a drug’s harm and benefits to be shared with physicians.  They use Sepracor’s sleep medicine, eszopiclone (Lunesta) as an example.  The company heavily promoted the drug through TV advertisements, spending $750,000 a day in 2007 and had sales of over $800 million in 2008. 

According to the NEJM article, what is less widely known than the iconic Lunesta moth is that the phase 3 study results on which the FDA based approval showed that Lunesta only led to subjects falling asleep 15 minutes faster (median sleep latency of 30 mins vs. 45 mins with placebo) and sleeping 37 minutes longer (median total sleep time of 6h 22 mins compared to 5h 45 minutes with placebo).  Although the Lunesta results were statistically significant, do the relatively modest clinical benefits justify the cost? 

This question is also increasingly being raised in oncology given the high price of novel agents and targeted therapies.  For example, a course of cetuximab (Erbitux) costs $80,000, yet only prolongs overall survival for patients with non-small cell lung cancer by 1.2 months.  Bevacizumab (Avastin) gained FDA approval for non-small cell lung cancer on the basis of a 2 month increase in overall survival, at a cost of $90,000 for a course of treatment.  A course of treatment with erlotinib (Tarceva) costs $16,000 for the benefit of an increase in overall survival in pancreatic cancer of just 10-12 days on average. 

While I am not saying that those survival increases are not worth the cost to patients to whom it gives hope and a few weeks longer to live, the high cost associated with them does raise hard questions that need to be addressed given that health care resources are not inexhaustible.  Physicians may need to become more involved in these tough cost/benefit decisions with patients, as resources and finances become more scarce all around and both payers and patients begin to wonder at the overall cost benefit being provided.

Of course, we should also remember that according to the Centers for Medicare and Medicaid Services, drug costs only account for approx. 10% of the total health care costs (hat tip, Rich Meyer), with physician and hospital costs taking up a significant portion of the budget, but comparative effectiveness could be applied across the board for in and out patient procedures and administration, not just medicinal products per se.

In the future, will we see the FDA only grant approval for drugs that are cost effective for the clinical benefit they offer much as NICE does in the UK?  At some point drug will have to justify their cost, as will hospitals and doctors for the fees they charge. 

Irrespective of whatever happens with the current bill trundling through the Senate sponsored by Max Baucus, health care reform in the U.S. sadly still has a long way to go.

Baucus, M. (2009). Doctors, Patients, and the Need for Health Care Reform New England Journal of Medicine, 361 (19), 1817-1819 DOI: 10.1056/NEJMp0910001

Sox HC, & Greenfield S (2009). Comparative effectiveness research: a report from the Institute of Medicine. Annals of internal medicine, 151 (3), 203-5 PMID: 19567618

Schwartz, L., & Woloshin, S. (2009). Lost in Transmission - FDA Drug Information That Never Reaches Clinicians New England Journal of Medicine, 361 (18), 1717-1720 DOI: 10.1056/NEJMp0907708

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Building a brand using social media

Here's an interesting and well thought out presentation from my Twitter buddy and fellow marketer, Morgan Brown.

Although he talks succinctly about his experiences building his own personal brand, it could just as easily serve as some useful tips and ideas about a life science or biotech company or a drug produced by a pharma company. After all, we all have to start somewhere and having seen the power of viral communication and PR as well as enlightened cancer patients engagement with the media, these ideas really resonated with me.

Take a quick look at Morgan's ideas and think about how using social tools and social media could apply to brand you, your product or your company:

How to build a personal brand using social media

View more presentations from Morgan Brown.

Image of Mike Huckman

It was particularly amusing to me to read this the week after I accidentally ended up on CNBC's Pharma's Market with Mike Huckman, who kindly invited me to provide a few sound bites on social media in response to the FDA's public hearing this week on the topic in these two short videos (with different soundbites):

You can also find out more about the event on Fabio Gratton's excellent site about the event, which crowdsources lots of great information from attendees (patients, Pharma, agencies and internet companies), presenters and those of us following remotely. 

Another Twitter buddy, Shwen Gwee, posted about the hearing and pointed to the links to the presentations, so if you're in the Pharma and Biotech industry and reading this blog or know of friends who are, these resources are all excellent background for getting started in your social media journey.

The FDA typically take 2-3 years to bring out new guidelines, if the recent one on REMS are anything to go by, so I doubt if we will see anything dramatic post hearing before 2011. 

In the meantime, it will be an interesting space to see how Pharma and Biotech develop new brand strategies, include aspects of social media to learn more about how patients really feel about their conditions and eventually begin to actually engage with consumers in more meaningful ways.  The vacuum at the moment with print but not internet guidelines will likely leave many companies anxiously watching on the sidelines for fear of being rapped on the knuckles by the FDA, as 14 of them were back in April for sponsoring branded Google ads.

After all, the best promoters of your product that you can ever have are not doctors and health care professionals, but happy patients. 

Why? 

Because they spread the word virally about your brand far more effectively and quickly than by any other method.  Of course, if they are unhappy with the medications or company's performance you can be sure that at least 15 other people will heard about that too.  Here's an excellent perspective from ACOR's Gilles Frydman on the same FDA meeting and why he was frustrated with the proceedings.

Branding and social media cuts both ways. 

The moral of the story is develop and and launch better, more effective drugs that really do make a difference to patients.

On the road

Last week was frantically busy with client meetings, CNBC and of course, the NY Chemotherapy Foundation (Greenspan) meeting, so my apologies for the paucity of blogs lately.  I had planned to write about some of the interesting presentations there but sadly, my flash key did not contain the expected saved presentations after receiving it back from the valet service :(.  Hopefully, I'll be able able to get them this week and update you all then.

We're rolling through the oncology conference season at the moment.

Today, I'm off to Boston for the AACR meeting on Molecular Cancer Targets, which promises to be full of genomics, stem cells and biomarkers as well as phase I data on interesting new compounds.

More updates to follow later this week!

Photo source: Flickr, Werner Kunz

links for 2009-11-14

• Knockdown of Chk1, Wee1 and Myt1 by RNA interference [Cancer Biol Ther. 2004]
  The kinases, Chk1, Wee1, and Myt1 are key regulators of the G2 checkpoint, which act directly or indirectly to inhibit Cdc2 activity. Show that RNA interference (RNAi)-mediated downregulation of Wee1 kinase abrogated an Adriamycin trade mark -induced G2 checkpoint in human cervical carcinoma Hela cells that are defective in G1 checkpoint response. Wee1 downregulation sensitized HeLa cells to Adriamycin-induced apoptosis.
  (tags: Wee1 G2 checkpoint Chk1 Myt1 RNAi CDC2)
• Cell cycle regulation by the Wee1 inhibitor PD0166... [BMC Cancer. 2006] - PubMed result
  G2 checkpoint abrogation by PD0166285 was demonstrated to kill cancer cells, there at a toxic highest dose of 0.5 muM in some cell lines for exposure periods of no longer than 6 hours. The deregulated cell cycle progression may have ultimately damaged the cancer cells. Used in mouse melanoma cell line model.
  (tags: Wee1 G2 checkpoint melanoma PD0166285)
• Discovery of gene expression-based pharmacodynamic biomarker for a p53 context-specific anti-tumor drug Wee1 inhibitor
  The inhibition of Wee1 kinase by a selective small molecule inhibitor significantly enhances the anti-tumor efficacy of DNA damaging agents, specifically in p53 negative tumors by abrogating S-G2 checkpoints, while normal cells with wild-type p53 are not severely damaged due to the intact function of the G1 checkpoint mediated by p53. Since the measurement of mRNA expression requires a very small amount of biopsy tissue and is highly quantitative, the development of a pharmacodynamic (PD) biomarker leveraging mRNA expression is eagerly anticipated in order to estimate target engagement of anti-cancer agents.
  (tags: Wee1 MK-1775 biomarkers mRNA p53 G2 checkpoint)
• A phase I and pharmacological study of MK-1775, a Wee1 tyrosine kinase inhibitor, in both monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors -- Schellens et al. 27 (15): 3510 -- ASCO Meetin...
  MK-1775 is a first in class Wee1 inhibitor that is well tolerated and shows promising anti-tumor activity in previously treated pts.
  (tags: Wee1 MK-1775 cancer phase I TKIs)
• Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents — Mol Cancer Ther
  Wee1 is a tyrosine kinase that phosphorylates and inactivates CDC2 and is involved in G2 checkpoint signaling. Reported the discovery of a potent and selective small-molecule inhibitor of Wee1 kinase, MK-1775. This compound inhibits phosphorylation of CDC2 at Tyr15 (CDC2Y15), a direct substrate of Wee1 kinase in cells. The data indicate that Wee1 inhibition provides a new approach for treatment of multiple human malignancies.
  (tags: Wee1 MK-1775 CDC2 G2 checkpoint signalling)