Tuesday, June 21, 2016

Patient-led design is finally coming of age

What patients think does matter. The pharmaceutical industry has made great strides in accepting that. They have even gone as far as understanding how patient views can be taken into account in drug development.

Delegates at the recent industry event in London heard that what doctors think is NOT the same as what patients think. Five years ago, this conference would not have happened. The industry was sure that what doctors think was interchangeable with what patients think: “Why would we want to speak to patients?” was the common refrain.

It’s hard to think of another industry where the views of the user have so recently been ignored. It is partly because the pharmaceutical industry employs a lot of doctors, and doctors have typically held the patrician view that doctor knows best. It’s also because drug development is complicated: designing, planning and implementing complex clinical trials in multiple countries means it can take 10 years to get a drug to market. You have to be sure that doctors want it and that regulators are likely to accept the results when the dossier of evidence is submitted. So it is understandable that drug developers have been averse to adding another variable into the mix by asking the users – that’s the patients – what they want.

It is early days but there are signs of change in pharma land. Like most change, a cultural change has to come first. Helping to drive that change is the quietly-spoken but not to be under-estimated Iris Loew-Friedrich, Chief Medical Officer of UCB. When faced with internal objections from legal or compliance that they can’t produce a straightforward, patient-friendly, informed consent form, she simply says: “I won’t take no for an answer. Show me the path and find a way!” A 20-page, dense legal dossier simply won’t do.

Novartis is taking a top-down approach in tackling what it sees as an industry at breaking point due to inefficiencies. The dream of Novartis CMO and Global Head of Drug Development, Vasant Narasimhan is an entirely paperless study. Overcoming internal resistance to change is key: “Usually you get six to twelve months of complaining. Then people move on to something new to complain about.”

• Amgen is trying more tests at home or with a GP rather than at a trial site

• Pfizer is involving the patient’s GP during the referral process, paying for their time in consulting a patient’s medical records to check if suitable for a particular trial

• Merck has improved trial design thanks to patient advisory boards; the company is also advising patients of trial progress along the way eg how many enrolled so far

• Lilly, a leader in the area of trial education, expects to have lay summaries of trial results by Q1 2017; it also runs CoLabs where a trial simulation is held to see if it works in the real world ahead of a protocol being approved.

There was general consensus at the conference that the industry is very good at being negative about the next two years and terrible at envisaging the next 10 years. 2016 could see a step change.

About the author:

Julie Walters, Raremark, the Founder, is a contributing writer for the Partnerships in Clinical Trials conference who has over 20 years of experience in the digital healthcare sector, including time spent as a news reporter and news editor at Sky News, Reuters TV and Good Morning.

Monday, June 13, 2016

Building a Foundation for Partnerships with Patient Communities

By April Schultz, Content Marketing Writer, Forte Research Systems

In a recent article published on the Forte Clinical Research Blog I define and highlight the importance of community engagement in clinical research. The article describes the need for sites and sponsors to communicate and engage with patient communities and advocacy groups. Such engagement empowers patients to become stakeholders in the industry and forms collaborative partnerships built on mutual respect and trust. These partnerships also aid the industry’s efforts to make trial design and conduct more patient-centric by allowing patients to have more input on the clinical research process. It seems many research organizations see the value in engaging patient communities, but are either unsure how to begin a partnership or are using ineffective community engagement methods. To successfully involve patient communities in the clinical research process, it’s important to develop a solid foundation for your community engagement initiatives. This means determining how your organization will communicate with patient communities and defining their role in the clinical research process.

A Foundation for Community Engagement

While the foundation for your partnership may differ based on the needs of each patient community, you can form the groundwork of your engagement initiative using these five steps as a guide:

1. Set clear goals

Your community engagement efforts should meet the needs of the patients involved. To do this, it’s important to define goals for the partnership and provide a solid guide to achieving those goals. Communication is key to determining what is appropriate and beneficial for both parties. During the initial stages of your partnership, actively discuss the needs and wants of both parties and begin to outline feasible goals for everyone involved. Throughout the course of the partnership, regularly assess these goals and the steps that have been taken to achieve them.

2. Establish expectations for communication and involvement

Partnerships often work best when guidelines for communication and participation are established upfront between all parties. Clearly establish how your partnership with the patient community will function, who will be the main sources of communication and what resources are needed for an effective partnership.

3. Gain a better understanding of the community

Take the time to learn about the attitudes and practices of the patient community you partner with. Make an effort to understand the group’s culture, how they prefer to communicate and other practices or attributes that make the community unique. Knowledge of these characteristics can help foster a stronger and more personalized relationship between you and the patient community and may encourage more responsiveness from the group.

4. Promote transparency

In community engagement, transparency is a two-way street. Patient communities should be encouraged to provide candid, open contributions during discussion and community engagement events. In return, it’s important you keep the patient community updated on clinical trial progress. While regulations certainly limit transparency for some trial information, it’s still possible to provide information on trial outcomes, relevant enrolling studies and other updates on the disease area.

5. Uphold a long-term commitment

To gain the most benefit from partnerships with patient communities, and to build a trusting and open relationship, it’s essential that both parties maintain a long-term commitment to the initiative. Overtime, communication between both parties will continuously improve clinical research as a whole and support patient-centric clinical trials.

Catering to the Individual

As stated above, these principles can and should be flexible based on the needs and qualities of each patient community or advocacy group you partner with. Maintaining a quality partnership and making your clinical trials more patient-centric means adapting your engagement methods to the needs of the individual patient community.

This flexibility is essential to both strengthen your relationship with the patients involved and to help you meet the unique challenges of every patient community. For each community or advocacy group, the type and frequency of communication could differ and the need for sponsor/CRO provided training could vary. For small or new patient communities, administrative staff may be minimal and thus communication via email or digital means may be strained. For global patient communities, it’s important to be wary of the country restrictions on communications with patients and physicians, particularly online and social media content.

When establishing the groundwork for your community engagement efforts, be sure to take into account the unique needs of the group you’re working with and attempt to build a partnership that proves mutually beneficial and convenient.


• https://www.hanc.info/cp/resources/Documents/Recommendations%202014%20FINAL%206-5-14%20rc.pdf

About the author:

April Schultz is the Content Marketing Writer at Forte Research Systems, a developer of clinical research software. In this role, she is responsible for the creation and direction of Forte’s educational materials such as blog articles, eBooks and webinars. She manages Forte’s content calendar, oversees content posted to the Forte Clinical Research Blog and works with presenters to host Forte’s monthly educational webinar series.

Wednesday, June 8, 2016

The Low Tech Approach to Recruitment (and Selling Your Car)

In my last post, social media was questioned for its potential efficacy in aiding recruitment efforts. Though I remain skeptical about the utility of outlets such as Twitter to drive significant improvements to research participation, earlier this week I found myself in an academic medical center with the same raised eyebrow… but this time around social media’s not so long lost cousin: the tear-off sheet.

Imagine the setting – a modern, bright and busy hospital lobby where I am pushing the button for the elevator. Right above the panel button? A tear-off sheet for a study at the hospital around diet. Every time I see a tear off sheet these days, I am either at the library or… the hospital. And what do I think of? The early 1980’s, waiting for food at our town's deli, reading the bulletin board to pass the time – music lessons, babysitting, items for sale.

But I digress… so after arriving up at the dermatology clinic for my son’s appointment on this particular day, we head into the exam room, door closes and… tear-off sheet: Do You Have Psoriasis? And since this sheet had a picture of psoriasis on it, my son was intrigued. What is this, how do you say it, who has this, does it hurt and so forth. Meanwhile, all I could think was… why is there a tear-off sheet, in a doctor’s exam room, where besides a medical professional there is also a computer running a multi-million dollar electronic records system?

Perhaps if my visit was for newly diagnosed psoriasis, I would have asked about the study after staring at the sheet for 20 minutes while I waited for my appointment. Or perhaps the doctor would have torn off the one-by-two inch piece of paper with a phone number on it and told me to call. Even thinking optimistically, it still struck me as so odd to be recruiting for a trial via paper, on a condition that is highly common in a dermatology clinic.

The “tear-off” approach to clinical trial recruiting seems so… transactional… when studies like this continue to show that patient attitudes towards clinical research tend to be at best uninformed (and at worst, fearful). It seems to me the best way to enhance recruitment is through the physician that already has the relationship with the patient – yet I admit that physicians are already pressed for time and balancing other patient demands. I can’t wait to hear what the experts at this fall’s conference have to say about the balance of self-identification for research versus physician engagement – and how technology, low and/or high, fits within.

About the author: Jennifer Crowley is a contributing writer for the Partnerships in Clinical Trials conference. When she is not working as a healthcare marketing and PR professional, Jennifer Crowley is mom to an eight year old son with cancer. His illness has largely driven her interests in patient advocacy, pediatric cancer research and personalized medicine. It's great to learn because knowledge is power!

Wednesday, April 20, 2016

Mobile Health: Exciting Technology for the Right Clinical Trial

By, April Schultz, Content Marketing Writer, Forte Research Systems

Partnerships in Clinical trialsThe clinical research industry is booming with new digital technologies and now, more than ever, the industry has the tools to make trials more patient-centric. In particular, the emergence of wearable and mobile health technologies have the potential to greatly advance patient-centricity in clinical trials through real-time data collection and participant engagement.

However, in order to maintain a truly patient-centric trial design, it’s important to make objective decisions about the use of mobile technology, with a study’s participant population in mind. As exciting as mobile health is, some technologies may impede the patient-centricity of a trial, making participation more difficult for some individuals.

How mobile health technology could revolutionize patient-centricity in clinical trials.

One of the most exciting capabilities of mobile health technology is the real-time data collection feature of some wearable devices and mobile apps. These features make data collection of everyday activities, such as exercise and sleep habits, more continuous and likely more accurate. Mobile apps allow participants to complete surveys in real-time, reducing recall bias. Patients can also self-track health-related items like blood pressure, diet, and more using commercial wearables or FDA-approved medical devices.

These mobile health capabilities could ultimately lead to a decrease in clinic visits or follow-up phone calls for participants, making it easier and more cost effective for people to participate in a clinical trial. It could also increase the scope of a trial by allowing individuals to participate from a greater distance, as travel requirements are reduced. This can lead to a more representative population by making it easier for people from rural areas to be involved in a study.

Participant engagement could also increase through the use of these technologies, as it’s now easier to communicate information and transmit surveys and other trial-related activities. If a participant has a trial-related question, it’s possible for her to check the mobile app and have the answer at her fingertips when needed, either through communication with study staff or in mobile documentation. A survey or activity could be transmitted and completed in real-time using the mobile health app, requiring little effort on the part of the participant. The participant can be continuously engaged with the study and provided the necessary information, making trial participation convenient and potentially more enjoyable.

Why mobile health should not be used for every clinical trial.

As described above, mobile health has a lot of potential in the clinical research space and could make the clinical trial experience much more patient-centric. However, these technologies may not be appropriate tools for every trial. It’s essential to be sure you're using tools that enhance the patient experience and ensure data integrity. For some patient populations, mobile health could prove detrimental. When determining whether mobile health is appropriate for your clinical trial, evaluate and characterize your participant population and their relationship with digital technology. Also take into account the feasibility of a mobile health study and assess whether you have the necessary resources to provide the best participant experience. Answer these key questions when considering mobile health for your study:

What is the age range of my participant population?

While younger generations are very adept with technology, seniors may struggle to use mobile health applications or devices. Using mobile health for an older demographic may require research staff to provide extra training. Such trial design could also inconvenience an older patient population as it may require them to perform atypical tasks and significantly alter the way they function throughout the day.

Do the majority of my participants have smartphones?

The demographics of your participant population, including age, financial status, location, as well as a variety of other factors, could influence whether they have access to a smartphone. If some of your participants don’t have smartphones, will you provide them the necessary technology? This could prove logistically difficult and limit the amount of eligible study participants in your target population.

Will my study use apps that participants already use? (e.g. Fitbit, MapMyRun, MyFitnessPal, other diary applications)

If your study requires you to create a new app, it could be difficult to find the resources and expertise to properly develop this technology. It may also require extra effort to encourage study participants to use the new application. Employing an application that is already widely used could reduce the amount of change required in a participant’s daily behavior, making the trial more convenient.

Is real-time data truly necessary for the benefit of my study?

The potential of mobile health and real-time data is exciting and it’s tempting to take advantage of the technology regardless of whether your study will truly benefit from its use. Critically evaluate whether the costs of using mobile health (such as those listed above) are worth the benefits of real-time data. If the benefits fall short, it may be best to opt-out of mobile health and design a trial better suited to the needs of your study and participants.

While mobile health technology could revolutionize how the clinical research industry conducts clinical trials, patient-centricity relies on the industry’s focus on building a positive participant experience. Regardless of whether mobile health is incorporated into study design, it’s essential to design each trial with the participant’s best interests in mind.

April Schultz, a contributing writer for the Partnerships in Clinical Trials conference
April Schultz is the Content Marketing Writer at Forte Research Systems, a developer of clinical research software. In this role, she is responsible for the creation and direction of Forte’s educational materials such as blog articles, eBooks and webinars. She manages Forte’s content calendar, oversees content posted to the Forte Clinical Research Blog (http://forteresearch.com/news/) and works with presenters to host Forte’s monthly educational webinar series.

Wednesday, April 6, 2016

Clinical Trials and Patient Recruitment: To Tweet or not to Tweet

Patient recruitment for clinical trials on social mediaLast December, this study showing that participation in oncology trials is basically abysmal made national headlines and helped create an interesting news juxtaposition – on one hand, a cancer moonshot is in the works, on the other, less than one in five patients today participates in vital, available research.

Enter Twitter, stage right. In an effort to identify possible novel approaches to improve recruitment results for not just cancer trials but all types of medical research, social media started to garner interest on the heels of those headlines. I personally found this suggestion both interesting and puzzling.

I am a Twitter user – and mother to an 8-year-old son with cancer who is currently enrolled in his third clinical trial (he’s doing great, btw). Prior to reading the Medscape piece, I would have never thought twice about Twitter as a source of vital medical information. For me, Twitter is a way to quickly catch up on current events happening locally, politically and around the pediatric cancer community.

So what is my opinion on Twitter as a trial recruitment source? Meh. First of all, consider who uses Twitter – according to Pew Research Center about 23% of all adult internet users, and a fifth of the entire adult population, uses Twitter. In the US, there are about 65 million Twitter users; usage is highest among urban residents, adults under 50 and people in upper-income brackets. Impressive certainly since the network is only ten years old, but how does its core demographic map to the types of patients that could benefit from a clinical trial?

I am not a scientist nor mathematician so I cannot answer my own question beyond the obvious – a lot of opportunity to reach patients, but what does that really mean because the medium is not the message. There is how to get the right trial opportunity in front of the right patient… and then how to spur action.

The context to social media usage as one experiences medical challenges is extremely nuanced. I belong to a community of cancer moms that will embrace social media for access to support via other families and communal knowledge, and will as quickly put it down when reality – that of others including full heads of hair and easily reached milestones – is emotionally too much.

So clearly I believe social media has a place in disseminating useful information but for Twitter or any social media channel to help with clinical trial recruitment, there is much work to be done. Where to start? How about by re-branding the term which far too many associate with “experimental medicine” or worse yet, “beyond help.” After all, what would you rather sign up for, a trial or an opportunity? If someone were to describe your personality as “clinical,” would that please you? When I tell people that my son is on a clinical trial, I often get a sad face – and yet I wholly credit our decision for his amazing progress.

All this to simply say, it’s fabulous that there is open dialogue about how to expand access to new treatment options for patients that could benefit by way of improved outcomes, less invasive therapies and more manageable side effects. Social media has a role, but it’s no silver bullet, particularly the sound byte laden Twitter. In fact, using Twitter as a lever in trial recruitment sounds like an interesting research study in and of itself to identify the most engaging sources and responsive populations. Hmmm now how to start recruiting?

About the author: When she is not working as a healthcare marketing and PR professional, Jennifer Crowley is mom to an eight year old son with cancer. His illness has largely driven her interests in patient advocacy, pediatric cancer research and personalized medicine. It's great to learn because knowledge is power!

Monday, February 22, 2016

Earn a FREE Pass to Partnerships in Clinical Trials 2016 - Become a Guest Blogger! | Boston, MA

Logo for the IIR's (Informa) Partnerships in Clinical Trials 2016

Partnerships in Clinical Trials 2016
October 5-7, 2016
Boston Convention and Exhibition Center
415 Summer St.
Boston, MA 02210 

Earn a complimentary all-access pass to Partnerships in Clinical Trials 2016 by serving as a Guest Blogger at the event. As a Guest Blogger, you’ll have access to the event’s comprehensive agenda attracting the leaders in clinical trials from around the world, right in Boston, MA in October.

We are looking for an industry expert with interest in the following topics:

• Data Standardization & Strategic Applications for Analytics; 
• Data Transparency;
• Patient Engagement & Recruitment;
• New Engagement Models in Patient/Site Interactions;
• Operational Implication of Risk Sharing Collaborations;
• Efficiencies in Strategic Partnerships;
• Partnering with Payers in Clinical Development 
• Innovative Outsourcing Strategies and Models- Small Biotech's/Small- Mid Sized

• Risk-Based Approaches in Clinical Development 
• Successful Interactions with Regulatory Agencies & Expedited Drug 
• Implementing Disruptive Technologies for Clinical Development  
• Clinical Operations in Global Trials 
• Site Selection in Global Trials
• Patient Recruitment in Global Trials

....and who would like to learn innovative strategies to navigate the transforming clinical landscape.

The premise is to provide PCT 2016 related blog posts (300-500 words), whitepapers, and overall light coverage of the event.

What you get is:

• You'll get a free all-pass to the annual Partnerships in Clinical Trials conference (valued at $2,995);
• Access to an extensive learning activities;
• Exclusive access to a networking community in the industry of your interest!

Apply today by sending your name, title, company, short biography and links to your blog or writing samples, along with a few sentences about why we should choose you to the Guest Blogger for PCT 2016 to Ksenia Newton at knewton@iirusa.com. We will review your submission and contact the chosen Guest Bloggers directly with more details.

We hope to have you join us in Boston!

*Guest Bloggers are responsible for their own travel and lodging. 

Subscribe to our blog or follow us on Twitter:  @PartnershipCROs and #PCTUS16 

Friday, November 27, 2015

Partnerships or Operating Models to Empower Delivery?

Chris Rull, Vice President, Service Provider Management Merck 

Over the past 5+ years, there has been a huge evolution in the strategic partnerships used to bring new therapies through clinical trials. I’ve witnessed this evolution from both sides of the partnership – working both within CROs and most recently within Merck..

One of the key challenges that sponsor companies face is in identifying the partnership characteristics the sponsor organisation needs most and being able to truly define their core and non-core competencies as desired.. Accomplishing this requires internal investment and analysis of organisational strengths and weaknesses. Through this process,  existing core competencies need to be identified along with opportunities to invest in maintaining and growing those competencies.

One of the most under-rated areas of partnership launch is Change Management, despite all the discussion around it.  Both parties need to be willing to invest, change and evolve with the partnership and make use of the expertise and experience that each bring. This of course requires the ability to really digest the cultural DNA and impact the organizational behaviours

Expectation alignment is also crucial - if internal strategy and external provision are not aligned, then no matter how strong the two partners are, challenges will arise.

And this draws back to the real goal of a true clinical development partnership – to bring new therapies to market and return efficiency to all parties. To do this, you have to achieve close alignment. All parties and players have to understand core strategy and the operating model in order to build a successful partnership.

Also essential is creating an environment within the partnership that empowers the functions accountable for the work. And you need a governance structure that is accountable and empowering and does not replace the functions that you are trying to optimize in the new structure.

In my opinion, one of the biggest red herrings is that many sponsors create or introduce strategic partnership as a result of external pressures that are misaligned to the above.  In these instances, regulatory reaction stands in the way of successful partnerships. Most of the regulations that relate to partnerships are self-imposed. Yet, if we spend the time with the regulations, they actually provide a great deal of flexibility to deliver your vision and purpose in a strategic partnership. 

In order to overcome these challenges, we have recently reorganized to deliver better service provider management. As head of this new function, my role is to provide clarity over who owns a relationship and ensure the relationship is managed effectively.

I’ve been a big believer in forums such as PCT-Europe for a long time; they are critically important as they bring people together from across the industry to discuss the issues in a very open and honest manner.

Friday, November 20, 2015

Data, transparency and the new EU regulatory environment

Thursday at the Partnerships in Clinical Trials meeting 2015 saw a panel of experts discussing questions posed by delegates on all manner of topics, such as the concept of "patient centricity" and industry's preparedness for the change, and a very interesting session on the implications of the EU Clinical Trials Regulation.

As I mentioned before, "patient centricity" is at the heart of this year's conference, and it certainly caught a lot of people's attention on Thursday morning. Panellists talked about technology, mobile devices, and new ways of capturing data, and suggested that we have only just begun to scratch the surface here. They painted a future where Google, Apple and the like will be the enablers of such technological advances, with patients monitoring their vital signs at home and conversing with their physicians by video and teleconference, rather than having to visit the clinic. After all, some patients may live a long way from the clinic and find it hard to come in as often as they would like.

But while being a homebird may suit some patients taking part in clinical trials, others will miss the chance to take some time out, the "human touch" of meeting their doctor face to face, the feeling of actually talking to someone properly rather than through an e-medium of some sort.  Probably the end result will be some combination of the two in differing proportions, with technology being seen as an adjunct - if a major one – to the current ways of doing things.

In any case, the patient will take a greater role in clinical trials, whether he or she likes it or not. Patients know best what is going on with themselves, declared Prof Brendan Buckley, CMO at ICON in Ireland. Patients, he said, would act as "data providers, with ownership of the process." "The idea of the patient as sub-investigator will be an important factor in the coming years, allowing us to better handle the very significant increase in data flow that we will have."

But he sounded a note of caution about moving too fast, suggesting that proper partnerships and joined up thinking were a prerequisite for true patient centricity, and this isn't happening now. For example, one CRO gets the data, another one gets the labs, and so on, and this makes it difficult to coordinate the various activities in order to achieve the sought-for patient centricity. What is needed is more partnership between CROs and pharma firms, so that the patient is prioritised. If outsourcing is done piecemeal it will be impossible to pursue this agenda, Buckley noted.

"Don’t get carried away with idealism," he cautioned. "There is a fundamental problem about how outsourcing happens – if the CRO gets the whole deal, and the full service process, there is some chance of advancing that agenda, but mostly outsourcing is technical and goes trial by trial."
It was noted that it's important to ensure that the protocol is well thought out, which apparently does not happen as often as it should. Some sponsors, it was suggested, put far too much into their protocols, and CROs need to make sure they are lean and uncomplicated.

And of course, again, don't forget the patient – or the regulator. The regulator's role is key here: companies are used to working to what regulators require in their guidelines. But in future, the regulators will increasingly want to know this: did you talk to the patients, did you ask them what they really need? And it's not only the regulators that have this in mind - the payers do too. If you have strong patient input, it will make your payer negotiations easier.

Which all goes to show that a joined-up approach to patient involvement, with continuous consultation, collaboration and co-ordination among all the key players, is the  way forward.

One of the afternoon sessions managed to throw some light on the less well-known aspects of the new EU Regulation that will take the European clinical trials scene by storm in a couple of years' time.

The session featured a very interesting presentation by Marine Dehlinger-Kremer of CRO SynteractHCR in Germany, who explained the many far-reaching changes that the Regulation will bring, not least the clinical trials portal and database, a single application to conduct a trial, and a great deal more transparency of trial data. As you may know, the application of the Regulation's provisions has been postponed from a notional mid-2016 to nearer the end of 2017, mainly because of the complexity of testing out the portal and database and undoubtedly a myriad other technical niceties.

Dehlinger-Kremer delved into some of the more technical and procedural changes brought posed by the Regulation, such as greater flexibility of monitoring (light or heavy depending on the nature and aim of trial), and the requirement for the sponsor to evaluate to the extent and nature of monitoring – which she said opens the way to risk based monitoring (RBM).

She also pointed out that failure to abide by the new transparency requirements would incur substantial penalties, although we don’t know yet what kind of sanctions the member states will be able to impose in case of non-compliance.

This was fertile hunting ground for Lawyer Peter Bogaert of Covington and Burling in Brussels, who keeps a very close eye on EU regulatory developments and has been known to represent the odd pharmaceutical company before the Court of Justice of the European Union.

He said that there would be a number of challenges with the implementation of the Regulation. For example, the new concept of a "low intervention trial", which he suggested could inadvertently lead to more off-label use.

A low-intervention trial according to the new legislation is a low-risk trial using an approved drug, for example, and with some administrative simplification with regard to informed consent, monitoring, damages, accountability, and so on. The criteria for such a trial are that you use the drug either in accordance with its approved labelling, or based on published scientific evidence on its safety and efficacy.

But if you apply for low-intervention status, the member state may have to confirm that there is indeed such scientific evidence or some existing treatment protocols that support this use. In this way, it becomes formalised, "which in some way is ratifying off-label use", Bogaert declared.

So, given that some member states are looking at greater off-label use, for example for economic reasons (as is happening in France and Italy with Roche's Avastin in wet AMD), "this will bring another dynamic because you could end up with more off label uses that are considered to be supported by scientific evidence," Bogaert noted. This is a completely separate question from clinical trials, but it could have wide ramifications, he added.

Something that is very germane to clinical trials is the amount of transparency the Regulation will bring to trial data, via the requirement for all studies to be registered and their results reported on the publicly accessible database.

The arguments about the benefits or otherwise of such openness have been well rehearsed. One is the assertion that miscreants might misappropriate the data for their own nefarious ends. The topic surfaced again at the discussion on Thursday, with suggestions that some companies in Latin America had used data released by the EMA to gain approval of their own drugs. Just how this would work is not clear (do you just cross out the originator product's name and insert your own?), but I'm willing to be convinced by some concrete examples.

Another argument leveled against the wider release of trial data is that it could defeat the wider objective of the new Regulation, which is to make the EU more attractive as a site to run clinical trials. Will fear of their data being released wholesale to all and sundry (it won't, or at least there will be safeguards in place to protect truly commercially confidential information) lead companies to flee Europe in droves? That remains to be seen.

What is more likely is that there will be knock-on transparency effects elsewhere. Noting that the EU is the first to ask for this level of transparency, Chiesi Farmaceutici's Antonio Ferrari thought the US and even the emerging markets might soon follow suit. "The US has started with its Sunshine Act, and its next steps will be transparency European style", he declared. Watch this space.

There was at least agreement that the new portal and database could do pharma firms a lot of good, given that it allows a single trial application for the whole of the EU and is also the conduit for inspection reports and trial results; moreover it will have a very nice dedicated workspace where the  member states and applicants can exchange information. 

Bogaert said the Regulation was, generally speaking, an efficient tool for ensuring the EU legislation on clinical trials was as strong as it could be, and that it would address many of the shortcomings of the clinical trials Directive it is replacing.

For those who are interested in the constantly changing EU clinical trial landscape, the hard work of getting the portal and database system up and running is now under way, and user acceptance testing is expected to begin in February 2016. Once that is done the system must be audited to ensure it is fit for purpose, a process that is expected to start around November and last until March 2017. Once the system has been given the all clear, the verdict will be published in the Official Journal, possibly in mid-year, and the whole thing will kick off six months later – ie, around the end of 2017.

It may be two years away, but that's not a long time where a project of this kind is concerned and you'll need to take time to ensure your IT systems and your thinking are up to speed. The advice to pharma companies and CROs? Start getting to know the system now. Many of your competitors already have. 

Thursday, November 19, 2015

This is what it means to be engaged with patients.

If the patients are senior citizens and travel to the trial centers using buses, don't book their appointments at 9.00 a.m. or after 3.00 p.m. Book them between 10.00 and 3.00 when the patients can use their free bus passes, and don’t have to compete with commuters, or put up with bloody, noisy, rude schoolkids.

Don't describe a protocol of monitoring for nasty drug side-effects in a cancer trial as a "wait-and-see" approach: patients with the disease will think that your approach is to “wait and see if they die”.
Don’t insist on a trial design that requires 22 hospital visits to take blood samples or assess lesion progress. Yes, its good to have data, but asking for 20 blood samples is going to give some patients the bleeding needle. Cut down the blood samples and have patients take photographs of their own lesions.

Don’t ask patients to fly across the country to the place where the trial-qualified staff are based: have visiting nurses – also trial-qualified – call in on the patients and do whatever is necessary.

Ask patients what they are really interested in as outcomes from a trial. The life-skills assessments that are routinely part of rheumatoid arthritis trials typically ask whether a particular treatment has helped a patient put on their socks and shoes, or cook a meal or undertake some task like walking across a room. But when you actually ask the patients what they want from an RA drug, they want to know if it will do something about fatigue: their fundamental problem is that they are so tired that they can't get out of bed - so putting on shoes and socks is just irrelevant.

These were just a few of the insights that came from the session "It all about the Patient – becoming more Patient-centric" at Informa's Partnerships in Clinical Trials meeting held in Hamburg. A panel of patient-engagers laid out some of the principles behind the new efforts from those who run and sponsor clinical studies to listen to the 'patient voice'.

It turns out that where it can be measured, patient-centricity can have some really positive effect of practical benefit to the pharma and clinical trial communities.

Replacing "wait-and-see" with the phrase "active monitoring" for a cancer trial approach increased recruitment almost overnight from 40% of target to 70% according to Sue Pavitt, a professor in applied health and translational research at the University of Leeds, UK.

Focusing rheumatoid arthritis trial assessments on fatigue, not dressing, gives patients the idea that the endpoint is relevant to them and aids recruitment, said Julie Hapeshi, a nurse-turned-trial-lead from the UK.

So far this new experiment of actively channelling patient input into clinical trial design is working out. Not only does it feel like it is the right thing to do, the results seem to be providing benefits not only for patients but for pharma, too.

In a lupus study run by AstraZeneca, patient consultation ahead of the trial not only reduced the number of hospital visits necessary for each patient by 25%, it also enabled investigators to get more out of the measurements they were taking on drug response and quality of life. So said Vincenzo Garzya, AZ's Patient-Centricity Excellence Director.

All of which excellent news really begs the question why this outbreak of common sense has only just happened in the in clinical trial community. Why haven't clinical trial organizations and pharmaceutical companies been listening to patients before? Why have companies only just begun to have Chief Patient Officers or Directors of Patient-Centricity Excellence? Why has it only just dawned on this industry that talking to its end-users might be good thing to do.

The answers that came back were revealing.  Panel chair David Wright, Clinical Trial Patient Engagement Technologies Lead at Amgen Global Development Operations (yes, he has a very large business card) said: "I guess we kind of thought we were [engaging with patients]. The fact that weren't only became clear when we started having problems in recruiting patients, and when the outcomes of trials were poor."

Melissa Jean Mottolo, a Roche Patient Recruitment Strategist said that it wasn't clear that regulators would give permission for this sort of contact. "We thought we weren't allowed to do it. Everyone told us that there was no point in going to the FDA because they are going to say 'no'. In fact we went, and they said 'yes'.

She also added that the internet has meant that patients have found it easier to get information on their conditions. "Dr Google has been very useful", as David Wright put it
Lesley Robson, who is Clinical Operations Manager at Cancer Research UK's Centre for Drug Development, thought the explanation lay in a changed attitude among patients: "Patients are getting a voice. What used to happen was they got ill, came in for treatment and took whatever they got and never challenged it. Now they are more confident that they should have a say."

There may be other explanations, too. I have often heard it said at pharma conference that the prescriber or the health insurance or the healthcare system is its customer, not the patient.
And when it comes to clinical trials, clinicians have served as gatekeepers to patients. “Gatekeeper” a polite term: “nanny” or “minder” or “pimp” might serve sometimes.

Those basic truths about the commercial and clinical realities may have penetrated too far in to the culture of the pharmaceutical industry and its suppliers/partners.

Its good to know that that may be changing, even if those waiting for the change have had to be – well – patient.

John Hodgson

John is Data Editor, Pharma at Scrip Intelligence @scripjohn john.hodgson@informa.com

Trudie Lang on the African Ebola trial

Trudie Lang, Professor of Global Health Research at the University of Oxford, UK, was involved in running the clinical trial of the treatment  used in the Ebola outbreak in West Africa. Ian Schofield spoke to Prof Lang after her presentation at the PCT conference, and asked her about the ground-breaking trial, what the experience taught her about our preparedness for future outbreaks, and what more the industry could do.

How did you first get involved in the Ebola  trial?

I was working on the drug trial – we ran a trial platform from Oxford funded by the Wellcome Trust. I have worked in tropical medicine for the last 20 years, mainly working on malaria, worms, leishmaniasis and so on, so we are used to setting up clinical trials in vulnerable populations in resource limited settings with low capacity on the ground. Previously I worked in Africa and Asia, 
and for this we worked in Liberia and Sierra Leone.

So what happened when you first went over there to get involved on the ground?

We worked with local investigators, with Médecins sans Frontières, with their treatment centres and with local clinicians, and we had a small clinical operations team that went into the tents to work with local healthcare providers and local researchers on the ground, so there was a lot of partnership. We were the sponsor, we wrote the protocol, planned the research, and gave as much support as we could, but what we really need to think about in the future is helping countries like Sierra Leone and Liberia to be able to lead these themselves. The research capacity gap is really the key, and it's important that they have more local capacity to allow them to operate their own trials. The only way they will do that is by working on other trials and having research as a normal part of operations in those countries, where now it really isn’t happening.

You mentioned the time taken to sort trial contracts out for the Ebola trial – what lessons does that hold?

Yes, we all know it takes far too long to set up any clinical trial and there are things you could do differently, contracts are always a problem, and then we were in this Ebola situation. But the same things come up – IP, time to publication, future pricing of drugs – so we should get ourselves sorted out and try to make sure we are prepared for the next time. We can have meetings with the WHO, have cross-stakeholder meetings, drop-down boxes and template contracts that we could pull off the shelf, but you know this takes work and time and resource and it is very, very difficult to get funding for this kind of research preparedness and capacity development, which is a massive gap.

Was it difficult to draw up a protocol in an on-site situation where there was a disease outbreak?

We are quite experienced in designing clinical trials to work in those settings and do quite a lot of work on being lean and agile, so I think actually the science was the easy bit. We were quite bold in our trial design and we had to work within the situation we were faced with: we couldn't do randomisation, for example – that would have been completely unethical – but we used a design that oncologists use, in that we were looking for big difference in drug effect so we could use historical controls and this was a perfectly legitimate scientific approach. But although there were big scientific challenges in terms of design of protocol, they weren’t necessarily logistical or organisational system challenges.

You mentioned it would have been easier to have access to commercial back up from industry.

I think it's more a question of commercial involvement rather than back up – they have an awful lot of expertise in running trials. I do a lot of research skills training, and I always say to people that a clinical trial is a clinical trial – most of us had never worked on an Ebola trial before and yet we were able to walk in and write a protocol and set up a trial because the skills you need to set up an Ebola trial are not really any different from oncology trials in Washington or Paris. But you need to be a trialist, and we need to be working much more in partnerships – industry has a lot to bring.

Have you been engaging with industry since this happened? Is there a forum where you can talk about this?

The WHO is writing a blueprint on what to do next time, and on the question of research readiness. I think it would be great to involve pharma more in some of this capacity development effort if there was interest, and of course these are emerging markets, so why not? Perhaps there is not the immediate commercial incentive to do so because it is not about a particular product, but it is about preparing the ground for clinical trials for a product. So should there be another outbreak and we want to test a vaccine, then it would be good to get some of this groundwork under way. So it would be interesting to work with pharma if anyone was wanting to get involved, but that might be a tall order because there is no in immediate commercial viability. But maybe some corporate social responsibility activities would be attractive to groups.

Have you learned enough from these experiences to really make a difference next time?

I think we made an enormous amount of progress, we ran trials within this outbreak and that has never been done before. We need to keep that corporate knowledge, if you like, between all the organisations and hope that we do better next time in having international leadership and so on.

Where might future outbreaks happen? 

Who knows, this is the thing isn’t it? We may well have another Ebola, a haemorrhagic fever type viral infection, a respiratory disease outbreak. There will be other outbreaks, and there will be other therapies and vaccines that will need to be evaluated, so we need to work at the global level to make sure we deal with some of these issues.

Wednesday, November 18, 2015

Partnerships, patients and what to do with data

It's the end of day one of the PCT meeting here in Hamburg. The sessions are over, company execs (well, some of them) have danced to the Beatles tribute band, and now it's time for a quick overview of the tastiest topics of the day.

The big theme of this year's event is "patient centricity" – getting patients more closely involved in clinical trials – which means finding out what they want from trials, taking their views into account in trial design, and how to work out where the patients are that will make your trial worthwhile running.

For me one of the most interesting presentations on this theme came from Vincenzo Garzya of Astrazeneca, who summed up "patient centricity" as "open and sustained engagement of the patient" to get the best outcome for them and their family.  

Patient centricity is now the focus across the healthcare landscape, Garzya said, noting the various initiatives under way such as the US Patient Focused Drug Development (PFDD), PCORNet – a large, national network for conducting clinical effectiveness research with a $250m investment, the European Medicines Agency's move to incorporate patients into its benefit-risk decision-making, and the UK NHS "No decision about me, without me" campaign.

That's all very well, but what is pharma doing about it? Companies apparently are becoming more interested in working with patients – and some would say that's none too soon – but as Garzya noted, it is a cultural change that "needs to come from the top." AZ, for example, had taken the initiative through forging a collaboration with PatientsLikeMe, which has access to data from around 300,000 patients and more than 2,500 conditions across a range of diseases.

David Wright of Amgen said there were pockets of patient engagement activity, but this was still really fragmented, and "not stitched together well." Companies don’t share information well internally among the different parts of the organization, he observed. "What does patient centricity actually mean?" 

The point was made that in practice it is quite challenging to get the right people round table to talk about what patients really want. In any case, there are two types of patient – those who are experts, for example because they are working actively in the charitable sector, and they have real value in terms of disseminating information to patient groups; and those who have to trek into hospitals to give blood samples or have biopsies taken, who feel tired or sick on chemo, and so on. These are the people you really need to talk to in order to get an idea of what is really on patients' minds, and the factors that will determine whether they are willing to enter a trial or not.

One session examined the concept of "social listening". Now, while this might sound suspiciously like something the intelligence services are doing behind your back, it is apparently a good way of finding out what your potential trial subjects might need before they do. It could involve scanning the social media communications of patients in a network, such as that for lupus, for example, to find out what their worries and priorities are and then addressing these issues when designing recruitment programs.

Also on the menu today was the future of clinical trial partnerships, in a session chaired in typically witty and provocative style by Dr Phil Hammond, UK GP and media personality rolled into one.
It seemed that partnerships weren't all they should be. Some speakers suggested there were no truly strategic partnerships that had stood the test of time, and that a new partnership model was needed. Sponsors needed to consider what they wanted the future landscape to look like, it was suggested. 

One issue that cropped up several times during the session was the fact that while new tools and technology are allowing us to gather more and more patient data, we don't know exactly what to do with it when we've got it. "The challenge is to transform that data so that we can read and interpret it," said Christian Tucat of CRO INC Research. "This will be the biggest challenge over the next five years." Others pointed out that the data is likely to be in many different places, and that ways would need to be found to bring it all together in one place.

The interesting question was asked: how far are the regulators enablers or limiters when it comes to clinical trials? Opinion differed, but the general agreement seemed to be that they should be involved in some way, as should all other stakeholders – indeed the Transcelerate initiative is trying to do just that in an effort to forge more meaningful partnerships. But what scope is there for greater collaboration among pharma firms? Could we see the day when several major companies come together to work on big trials for, say, combinations of their own drugs? One day perhaps, but not quite yet, it seemed.

At the end of the day, the impression I came away with was that there is a great deal of potential for collaboration among sponsors, CROs, patients, regulators and other stakeholders when it comes to efficient and practical clinical trial design, but that there is still some way to go before this becomes a reality. Where the roadblocks are depends on where you stand, but there seemed to be a strong feeling that sponsors need to be less cautious, more open to collaboration and more prepared to bring the patient much more nearer to the core of the clinical trial process. 

An early summary of PCT's first day

Some very interesting presentations on PCT's first day. A a quick summary of the hot issues so far, with more detail to follow in a subsequent bulletin.

We may be getting more and more patient data through new technological tools, but how do we analyse and interpret all that data? Where is it all stored and how do you access it?

Do regulators help or hinder the trial process? They don't help us, but neither do we help ourselves, said one speaker; for others this is the perfect time to partner more closely with the regulators.

The folk from Transcelerate explained their approach to getting stakeholders together to reduce  the cost and risk of running clinical trials. They also suggested that getting big companies to collaborate to run bigger trials is a key goal - but will it ever happen?

What about the patient perspective? "Patient centricity" is the new buzzword: a whole afternoon here was devoted to the importance of getting the patient's view all the way along the development pathway, so the idea must be making waves (and not before time, some might say).

Another engrossing presentation: Trudie Lang of Oxford University on the difficulties of testing the Ebola vaccine in Africa and the lessons learnt. We'll be bringing you an exclusive interview with Trudie, so watch this space.

Ian Schofield
Scrip Intelligence

Tuesday, November 10, 2015

Experts gather to address key clinical challenges at PCT-Europe

Informa Life Sciences is predicting record attendances at its Partnerships in Clinical Trials(PCT) Europe Conference in Hamburg, 17th to 19th November 2015. Experts from all over the world are preparing to gather in Hamburg to address the issues facing the complex partnerships involved in delivering patient-centric clinical trials and bringing new therapies to market.

This year, PCT-Europe 2015 will focus on delivering fresh and inspirational stories and speakers discussing solutions to the challenges faced by all those involved in delivering patient-centric clinical trials.
With outsourcing of clinical trials efforts increasing at a rate of over 40% a year, making partnerships work for everyone involved is of critical importance to the industry and those relying on the development of new therapeutics.

Ensuring alignment between the multiple parties and stakeholders involved in recruiting and caring for patients, collecting data and delivering meaningful submissions to regulators is a significant and multi-faceted challenge.

These challenges will be addressed in detail at this year’s conference that will be held at the CCH Congress Center. With more than 120 speakers from leading biotech, pharmaceutical and contract research organisations (CROs) attending, PCT Europe is a must for any industry professional.

Tuesday, November 3, 2015

Biomarkers in Life Sciences/Healthcare Convergence Lead to Better, More Personalized Healthcare

By MaryAnne Rizk, PhD., Vice President, Global CRO Partnerships, Oracle Health Sciences

One of the great challenges for the effective use of pertinent data from multiple sources is to be able to integrate, standardize and normalize those data, which include clinical, outcomes, financial, administrative and genomic data into a single repository upon which one can query and analyze to create actionable information. What’s needed to advance personalized or individualized medicine is the effective utilization of all available data to develop the optimal treatment plan for an individual patient for improved outcomes. Genomic biomarkers are becoming the Holy Grail for Pharma and Biotech companies to find these right treatments and for clinical care providers to improve patient care.

In many diseases, there is a direct link between certain genes and the disease itself.  These genes, as well as the proteins that are derived from them, are collectively referred to as “biomarkers” and often are indicative of the presence of a disease, the potential to develop a disease or indicators for targeted drug treatments. The costs for whole genome analysis, targeted DNA sequencing and other molecular diagnostic tests are dropping, the sophistication of the tests is increasing and more tests are being developed, all of which are having a positive effect on R&D and clinical care. With biomarkers being the first step in personalized medicine, Pharma and Biotech companies are aggressively incorporating biomarkers into their R&D efforts and clinical research programs. 

The Center for Drug Evaluation and Research (CDER) at the FDA recently boasted of the Department’s strides in precision medicine, demonstrating that since 2012, CDER has approved thirty targeted (biomarker –related) therapies, eight of which were approved in 2014. Personalized medicine is rapidly coming of age, with 42% of all compounds and 73% of oncology compounds in the Pharma development pipeline have the potential to be personalized medicines. In addition, Pharma has nearly doubled their R&D investment in personalized medicines over the past five years, and expect to increase their investment by an additional one-third in the next five years. Also, Biopharmaceutical researchers are predicting a 69% increase in the number of personalized medicines in development over the next five years.

The importance of biomarkers in personalized medicine is to define which patients would benefit most from which therapies, at the right dose with the lowest risk. During clinical development, Pharma and Biotech companies are now using the presence or absence of biomarkers as key inclusion/exclusion criteria for their clinical trials. Taking this approach, along with greater use of adaptive study designs, are being employed to improve the chances of including the right patients that have the best chance of demonstrating a beneficial effect of the experimental drug being tested, thereby reducing the time, cost and risk of development and accelerating the availability of effective treatments sooner. 

As clinical development proceeds, Pharma, Biotech and CRO’s are expanding their data needs to include clinical outcomes, comparative efficacy and cost effectiveness. Historically, these needs could only be partially met, since the technology to effectively integrate these data from multiple disparate sources didn’t exist, or was too cumbersome.

Personalized drug safety, the practice of determining which patients are more likely to experience a serious adverse event, is another area of focus for Pharma, Biotech and CRO’s. Patients who experienced a serious adverse reaction to an experimental drug in a clinical trial are evaluated in an attempt to identify biomarkers that may be correlated to that event/reaction. Once a biomarker has been shown to be correlated with an untoward event, that biomarker can be used to exclude patients from being treated with a given drug or prevented from being enrolled in a clinical trial. The effective use of biomarkers as a risk/safety mitigation tool can be extremely beneficial by excluding patients that may be at risk for an untoward event from being exposed to the drug, thereby avoiding adverse events that could be very costly. 

In any clinical research project for any Pharma or Biotech company, mitigating risk, reducing time, minimizing cost and improving the probability that the right patients will be enrolled to optimize beneficial effects are critical to the overall success of the project.  For the scientific and healthcare community, it’s exciting to see precision medicine and the use of biomarkers “going mainstream” since improving patient care, optimizing outcomes and reducing costs are common goals.  Cracking the code on personalized medicine takes a true collaboration between Pharma/Biotech and Healthcare organizations.  Creating a technology platform that fosters the collaboration of all key stakeholders, Pharma/Biotech, Healthcare and CROs provides the basis for the growth of personalized medicine.