Data Sharing in Drug development - Benefits

Access to full, appropriately de-identified datasets from clinical trials can benefit the biopharmaceutical industry by improving the efficiency of drug development, enhancing comparative-effectiveness analyses and reducing duplication of effort among trial sponsors.

1. Not sustainable

Industry is right to be concerned about the sustainability of the existing drug-development and business model. 

In Pharma Industry, the timelines and costs of clinical drug development are increasing relentlessly, and the attrition rate of assets in development remains high.

At the same time, growing cost pressures in all healthcare environments are forcing restrictions on drug use, aiming to limit coverage only to patients who can be expected to benefit from a given intervention and for whom that intervention is clearly cost-effective. 

2. Design and analysis

Access to the full datasets of completed clinical studies would, in the first place, lead to improvements in the design and analysis of subsequent trials.

To quote an example, available information about numerous variables can be used to identify and validate prognostic factors. Relevant validated prognostic factors can then be selected for use in the stratification of subsequent trials to reduce unwanted variability, minimise type I and type II error rates, and inform pre-specification of statistical modelling and subgroup analyses.

The identification and validation of factors that predict treatment response also enable active sampling or population enrichment in subsequent clinical trials, to avoid having a treatment appear ineffective because the trial has been conducted in a diluted population.

Enrichment can reduce sample sizes as it makes larger treatment effects easier to detect. 

The inclusion of patient-level data can also generate comprehensive, quality-controlled databases with potential to inform future research projects and questions.

3. Heterogeneity of effects

Moreover, lessons from past clinical trials about the heterogeneity of treatment effects will not only streamline drug development but may also enhance a drug’s value in the marketplace. 

Identifying a population with high unmet need in which a new treatment may be more cost-effective than other available options can help sponsors during reimbursement negotiations.

4. Comparative effectiveness

They also emphasise the growing importance of comparative-effectiveness insights to patients, prescribers and positioning of new medicines.

Data from individual patients on both outcomes and co-variates can alleviate some of the weaknesses of this approach, such as the need to make assumptions about heterogeneity and consistency of effect on the basis of the summary data that are currently in the public domain.

Wider access to patient-level data from clinical trials will allow sponsors to present more robust comparative-effectiveness information about their product soon after licensing and at a very limited cost compared with head-to-head trials.

5. Doomed from the outset

Finally, one of the “inherent inefficiencies” of data secrecy is the repetition of trials and projects that are doomed from the outset. 

Drug developers may continue to pursue a given target even though clinical trials conducted by others have demonstrated the effort’s futility. With patient health at risk and limited resources for research, the high opportunity cost of clinical-data firewalls is difficult to justify. 

6. Addressing concerns

Given the array of potential uses for patient-level data in facilitating research and development, it is surprising that few drug developers have been sharing data voluntarily.

Commonly voiced concerns, they note, include the risk of jeopardising patient privacy, of clinical trials being misinterpreted due to “inappropriate” analyses, and of commercially confidential information being disclosed to competitors.

Secondary analyses

While a “truly open” approach to clinical-trial data does carry a risk of inappropriate secondary data analysis and conclusions, this risk “exists for any type of secondary analysis, regardless of the nature of the data.

Clearly, though, legitimate interests in intellectual property and the protection of private investments “must be weighed against other legitimate interests, such as transparency regarding the outcomes of clinical trials and the protection of public health”.

Striking the right balance of these interests, they insist, “is a duty for all responsible stakeholders involved, not just for regulators.

Technology Impacts in Clinical Research

Much advancement in technologies such as Open standards, Cloud computing,  Mobile access and tablets (computing devices) have been utilized in the life science sector especially in Clinical Research Industries. However, despite the cost and compliance advantages offered by many of these advancements, clinical research firms are still slow in adopting them. Research conducted across various analysts shows this dynamics is about to change.

Technology Shift:

In the recent years, many CRO’s and pharmaceutical companies are now meeting compliance regulations with less complexity and cost when compared to the past. There is also a technology shift that the peer organizations are starting to take advantage of. A very good examples is that Sanofi Aventis, when the company first adopted an open platform, it estimated the changes being made would remove over $9 million per year in costs associated with time wasted in managing documents.

Open Standards:

Various surveys were conducted to determine the impact of these technology shifts on clinical research. One of the main impacts was on Microsoft’s SharePoint and the other on adoption of electronic trial master files (eTMF). This shows us a very clear and increasing shift to open software platforms. Looking back, this trend started in 1990’s when clinical research industries started managing documents electronically ( REF: 21 CFR Part 11). This is a stark difference from the newer solutions hitting the market which now reside on open, non-proprietary platforms.

In its SharePoint for Life Sciences Survey, NextDocs asked if firms were scaling back on proprietary systems in favor of more open-standard platforms like Microsoft’s SharePoint. In 2012 only 22% of respondents said yes. By 2013 that number had grown to 35%. The survey also asked what system most firms were replacing when they made the switch to SharePoint. Almost half of those surveyed were replacing EMC’s Documentum, followed by Oracle WebCenter, OpenText Livelink, CSC FirstDoc, Master Control, and IBM Content Manager.

EMC’s Documentum is a multipurpose document management solution not specifically built for the life sciences industry. In Earlier days, pharma companies had large IT budgets and IT staffs, and were growing fast. Today that growth rate has been cut in half, and many applications no longer meet the needs of customers looking for mobile access and cloud computing capabilities. Those same firms are now finding commercial, off-the-shelf collaboration platforms from trusted vendors like Microsoft which can run applications purpose-built to manage clinical trials.

SharePoint And eTMFs Reduce Cost

A second trend is platforms like SharePoint managing regulated content, a space that hasn’t traditionally used SharePoint. Most life science companies have SharePoint running somewhere in the organization. Historically, companies have been using SharePoint to manage their intranets and create project team sites. While these applications were important for collaboration, they were not regulated.

It is been observed that the use of SharePoint in clinical trial document management, FDA submission documents, clinical trial activities, change controls, and complaint management has tripled when compared to earlier. These are areas where firms are required to show they have an audited process, and SharePoint can be used to prove compliance.

The third trend is the use of electronic trial master files (eTMFs) to manage the large volume of clinical trial documents. Over half of the companies participating in the survey indicated they were using some type of eTMF for all or part of their studies, or were currently evaluating it. Only one-third of respondents had no plans to use it, or weren’t sure.

This below example is the best one to show how important is eTMF and its reduced cost. 

In 2007 Sanofi looked at the paper generated from one of their trials. One trial can easily generate over 25,000 documents. When you consider that a company like Sanofi will run anywhere from 150 to 200 clinical trials per year, moving to electronic master files will result in a tremendous amount of savings both in cost and in human labor required to manage all of that paper.

Advantages of eTMF:

• Increased productivity.
• Improved audit results.
• Reduced time to prepare study milestones and events.

Mobile Devices & Cloud Computing Simplify Access

The fourth and fifth trends involved the increased use of mobile devices and cloud computing in clinical trials. While eTMFs will substantially reduce the amount of paper in clinical organizations, the content of those documents still has to be reviewed by investigators around the world. More and more, those investigators want to access content using mobile devices like iPhones and tablets. This trend creates additional challenges for firms.

Access to eTMFs has to be regulated, both in terms of who can access them and how they do so. A clinical study might take place at 50 different sites, and each site will have several investigators. These investigators, typically physicians, don’t want to have to log into a content management system. They just want to quickly find the document they need, sign it, and submit it. They realize the easiest and quickest way for them to do this is via a mobile device. The use of tablets in clinical trials is not common right now, but the industry believes it will soon be taking off.

Finally, the increased use of cloud platforms for regulation and compliance. For years companies were not sure if the cloud could be used for compliance, or if the FDA would accept its use. Now it is believed that more clinical firms are finally getting past the fear stage and adopting the technology. One of the big drivers of that change is the need and desire of clinical firms to collaborate with individuals outside the company, including investigators, CROs, universities, and pharmaceutical and medical device companies.

What is holding companies back is not the cost of these new technologies, but the fear of going to something new. But we are to the point where companies can see the advantages of going to an open, collaborative platform. Up until now, dealing with technology issues has been like playing Whack-A-Mole. Each time you knock down one issue, another one pops up. CRO’s are aware of the limitations of their systems, which is allowing market analysts to help them understand how open solutions fit their specific needs, and help them to finally get past that inherent fear of change.

Indian Pharmaceutical Industry - Main Hurdles

Main hurdles in Indian Pharmaceutical Industry

During the recent years, there has been serious concerns among US businesses and lawmakers over IP in India where Clinical Trials, Infrastructure and Policies are the biggest hurdles in driving research and development in Indian Health care Sector. While both global and Indian industry leaders opine that India's intellectual property (IP) situation needs to be addressed and clarified, they have highlighted that in fact clinical trials, infrastructure and policy are the biggest obstacles for India to meet its potential of driving R&D innovation at scale. 

Recent reports from 'Crossing the Next Horizon: Will India play a Meaningful Role in Global Biopharma Innovation?'. lays out the myths and facts about the biopharma innovation in India. The findings would help senior management of biopharma companies fine tune their R&D strategy and help leverage India's pockets of R&D strengths.

According to excerpts of the report, many global R&D heads and CEOs emphasise the need for Indian companies to shift from 'deals' that offer only cost arbitrage to alliances that focus on innovation, quality and service. The report notes that emerging markets such as India can play a significant role in collaborations, providing not only more cost effective innovation, but access to new talent, technologies and assets to fill currently dry pipelines. 

The Indian healthcare sector has tripled in size in the last decade from USD 23 billion in 2002 to USD 70 billion today, but India continues to lag peer countries in spending, outcomes, health manpower and infrastructure, it said. Within healthcare, the Indian pharma market has also shown strong growth from USD 6 billion in 2005 to USD 18 billion today and is expected to grow to USD 45 billion by 2020.

Discussions with several global and Indian industry leaders indicate a widespread acknowledgement of India's potential for R&D innovation and while the fundamental drivers of the 'India advantage' exist, the opportunity has not played out as expected.

India holds a vast and largely under-tapped pool of drug innovation resources and capabilities. 

While the report recommends that the Indian government fix and clarify relevant policies and regulations around clinical trials and IP; focus cross-border and cross-entity collaboration on building talent and infrastructure across clinical trials, PI training and basic research. These strategic partnership not only enhance to overcome the hurdles of healthcare sector in India but also improve the quality of life.

Greater use of electronic medical records could help pharma companies cut recruitment times for trials and reduce development costs.

Main Outcomes:

1. Use of patient data collected by healthcare systems can identify potential clinical trial participants more quickly and with better precision than traditional procedures.

Example: Dr Eriksson (pictured), a former senior director at Merck & Co, noted that a recent study by Parexel managed to knock 12 months off the estimated 24 month recruitment time.

2. Such efficiency has the potential to cut down research costs tremendously, with the price of getting a drug to market now well over the oft-quoted $1bn figure.

3. The use of electronic medical records – the medical history of a patient kept in a digital format – to support clinical trials has been encouraged by other prominent figures in healthcare, especially in the UK, which, in the NHS, has a healthcare system that covers the entire country.

4. Establishing EMR will attract new clinical studies across UK. 

5. Also, how use of this data can help, saying that researchers had the ability to use electronic medical records to accurately isolate a specific cohort of patients with a certain condition, and then run this cohort against patient profiles – such as demographic, age, gender, etc – to have representativeness in clinical trials.

6. Being a crucial development, said Dr Eriksson, considering that between 50 and 65 per cent of potential clinical trial participants fail at the screening stage because they are found not to meet one of the study's crtieria.

7. Ease of Market Access.

8. This protocol can then be used to run a report to find out where relevant patients are being treated and what patients are being treated by physicians registered as investigators, while electronic medical records can then be used to demonstrate suitable patients to investigators.

Drawbacks: 

One of the greatest burdens in using electronic medical records is uptake and compatibility among healthcare systems, which varies between different countries.

Alternates: 

This is changing, however, according to Dr Eriksson, who said that countries are now following the route of South Korea and Turkey who became the first two countries in the world to have a healthcare system with 100 per cent electronic medical records that are connected to each other and managed by a central office.

The situation is also improving in the US, where uptake has increased since President Barack Obama introduced an order that all healthcare providers need an electronic medical record system by 2014.

By 2020, I imagine the whole world will be using electronic medical records. Healthcare systems are also becoming more proactive in developing partnerships in clinical development, according to Dr Eriksson, who heads up a department at Parexel that is focused on building alliances between the CRO, industry and healthcare providers.

It is important to have partnership with healthcare and investigator networks to improve the services in the medical industry. 

New CRF in Dublin, Ireland

A €7 million clinical research facility has opened at St James' Hospital in Dublin, Ireland, to carry out early- and late-phase clinical trials across a range of therapeutic categories. The unit is a joint initiative between St James' and Trinity College Dublin, with funding from the Wellcome Trust and Health Research Board of Ireland, and launches with 25 research projects underway or at the planning stage.

These include an EU-funded project to develop a vaccine against hepatitis C in HIV-positive patients, as well as new therapies for oesophageal cancer, diabetes and Alzheimer's disease. This new facility is good news for patients as it will allow the testing of new and innovative therapies, technologies and products and should increase the speed at which these innovations and discoveries enter health care services.

The unit houses a research pharmacy capable of safely compounding cancer drugs and handling novel gene therapies and vaccines, in-patient isolation rooms to nurse patients with infections or compromised immune systems, and a neuropsychology suite that will enable high-quality studies of brain activity and cognition.

The Wellcome Trust provided €7.3 million in funding to construct the CRF, while the HRB has earmarked €5 million to cover operating costs and €8.2 million to fund projects carried out under the banner of the Dublin Centre for Clinical Research (DCCR). The DCCR provides the facilities and trained staff needed to support collaborative clinical research studies across Dublin involving the Trinity College, University College Dublin and Royal College of Surgeons in Ireland (RCSI) medical schools and their associated teaching hospitals.

The facility, placed at the interface between university and hospital, is an early model for the newly announced hospital groupings and academic medical centers. The unit will provide "greater integration between the healthcare agenda and the teaching, training, research and innovation agenda.

Decline in Clinical Trials for Cancer

The fall in the number of clinical trials in India together with blockbuster pipeline drying up from the global pharma majors are seen to seriously impact the access to newer drugs to treat tobacco related cancers. The fewer number of novel drugs is posing to be a huge challenge for oncologists to treat the growing number of cases.

With the stringent norms coming in from global regulatory majors where trial designs mandate use of electronic records, maintenance of total transparency from ethics committee registration, patient recruitment, monitoring of adverse drug reactions and reporting deaths have all resulted in a grinding  halt to novel medicines. There is a serious lack of the newer cancer drugs to treat oral cancer affecting the larynx, pharynx, food pipe, largely attributed to tobacco chewing and smoking, stated the cancer specialist hospitals.

Many patients in the early and late stages of lung, head and neck cancers were agreeable to be part of clinical trials because they did not have to pay for drugs which are expensive. 

Dr. S Krishnamurthy, Professor, Surigcal Oncology at Kidwai Memorial Institute of Oncology (KMIO) expressed that Kidwai was the centre for many of the cancer trials until recently. Also due to government restrictions, there are hardly any human studies being carried out.
As a result we are now forced to prescribe the patients with the existing drugs to treat cancer. Particularly for lung cancer Gemcitabine/cisplatin is among the most widely used regimens. There is also a class of platinum-containing anti-cancer drugs like carboplatin and oxaliplatin which are also popular along with Doxorubicin that is part of a group of chemotherapy drugs.

For the affordable patients, targeted therapies are seen to be the answer to treat cancers affecting the lung, head and neck areas. Currently the most opted commonly used drug is the epidermal growth factor receptor (EGFR) which is known to provide a big relief in terms of symptoms control and also enable patients to lead a somewhat normal life. 

While lung cancer which affects 90 per cent of the smokers is the most difficult to treat and a paucity of clinical trials is affecting patient care. For oral cavity and other tobacco induced cancers, oncologists would prefer to first consider surgery and remove the diseased cells. The second and third options put before the specialists are to go in for radiation and then chemotherapy. But these are known for side-effects. Now with a fall in the number of trails, oncologists are looking at targeted therapies where monoclonal bodies (MAbs) are seen to be an answer.

Oral Vaccines against Diarrhoea

A drinkable vaccine against diarrhoea causing bacteria is soon a reality, according to the Sahlgrenska Academy in Gothenburg.

Researchers at the institute have developed a vaccine against Enterotoxigenic Escherichia coli, one of the leading causes of diarrhoea in undeveloped nations, as well as among travellers. It has the potential to help millions of people around the world, say the researchers.

The researchers tested the vaccine on 129 healthy people. Three out four of the vaccine recipients responded to all five of the primary vaccine components. In addition, 85 per cent of subjects who received the vaccine co-administered with an adjuvant showed significant immune responses to all vaccine components.

The vaccine was also proven to be safe with few and mild side effects, say the researchers. Clinical trials are now planned in the future.

Each year the Enterotoxigenic Escherichia coli causes around 400 million cases of diarrhoea, of which around 300,000 are fatal. The majority of those affected are under 5 year of age, according to the Sahlgrenska Academy.

Globalized Clinical Trial Solutions

The discussion here is that 'Is it positive to have more globalised clinical trial locations’?

Clinical trial locations are no longer restricted to a handful of key scientific bases in the UK, US and Europe. In the first of our occasional series, we look at how this movement has impacted global skills needs. 

The horrific incident at Northwick Park Hospital in 2006 that left clinical trial lists critically ill not only shocked the British public, it coincided with a shift change in the type of subjects happy to take part in certain kinds of drug trials and, more pertinently, where those trials are now held. 

Emerging markets in Japan, Korea, India, Mexico and various Eastern European countries have radically changed what clinical trials are happening where, with whom and why. 

Local regulations are increasingly stringent and the sheer cost of running a clinical trial in the UK, France or the US is making it harder to justify and secure funding. 

Moving East is one way of getting round this. Foreign clinical trials create job opportunities for researchers, scientists and medical personnel. They can also lead to new therapies being available. 

Some locations make better sense for particular drug tests because of the prevalence of certain conditions and illnesses in those regions. 

And, of course, there can be financial advantages for companies dealing with budget restrictions. According to one study, the cost of conducting biomedical research in China is only around 20% of the cost for similar trials in the West.                                             (Source:http://www.pharmafocusasia.com/clinical_trials/biotech_trials_asia.htm) 

Is this a good thing? We know there are real concerns about how different populations affected by poverty, prevalent diseases etc. may metabolise drugs differently. How does that affect the skills needed to apply these study results to medicines on sale elsewhere around the world? 

Then there are the regulatory hitches and differences in local legislations. So do you feel it is positive to have more globalised clinical trial locations? Are pharma companies exploiting a less aware set of subjects and are the results always transferrable and reliable?

Importance of Regulatory Science

When someone uses the word “science,” we might think of chemistry, biology, or physics, to name just a few fields.

We probably wouldn’t think “regulatory science.”

But it’s a field that has a big impact on the daily life of the average consumer. The breadth and scope of FDA’s regulatory oversight is extraordinary, touching the lives of every individual, through the food we eat, the medicines we take, and the medical devices we use.

That oversight is based on the sound science, called regulatory science, that is the foundation of FDA’s day-to-day decisions. Scientists throughout the agency research the development of new ways to evaluate FDA-regulated products.

As new discoveries yield increasingly complex products, the agency must be able to make science-based decisions that result in sound regulatory policy.

And there’s a need for speed.

There’s a gap between research and discovery—which is ongoing and very vibrant—and the actual delivery of products to the market and to those who use them. So this is an area that we think is critical for making that link between discovery and the actual product on the market.

Focus Areas within Regulatory Science

In August 2011, FDA released its “Strategic Plan for Regulatory Science,” an initiative that identifies eight priority areas essential to the continued success of FDA’s public health and regulatory mission. The plan is wide-ranging, with its target areas including personalized medicine, food safety and medical countermeasures to protect against threats to U.S. health and security.

• Personalized medicine involves the development of treatments that are tailored to an individual patient or a group that shares certain genetic characteristics.
  
  
  Medical science is now capable of creating treatments that are guided by the patient’s unique genetic information, In June 2011, FDA approved a novel genetic test to determine if breast cancer patients are candidates for Herceptin drug treatment. 
  
  
  These treatments can be specifically tailored to provide individuals with maximum health benefits while posing the minimum of risks. We’re approaching an era when ‘one size fits all’ medications will no longer be the doctor’s only option.
   
• FDA’s long-range goal for food safety is to prevent food safety problems from happening in the first place. But the agency also needs the tools to contain problems if they do occur and to understand how they occur so they can be prevented in the future.
  
  
  Food safety can be affected at many points along the farm-to-table chain, and our goal is to establish preventive controls at each step to minimize hazards. But success requires the most advanced science and technology to know what preventive controls are needed, to detect problems when they happen and to minimize illnesses when outbreaks occur.
  
  
  The need for state-of-the-art know-how was shown in 2010, when an oil rig explosion dumped more than 200 million gallons of crude oil into the heavily fished waters of the Gulf of Mexico. When the crisis began, the chemical test to confirm that seafood was free from harmful oil residues took about a week to run—too long for the large number of samples that had to be analyzed.
  
  
  To solve this problem FDA scientists, working with state partners, developed a new testing procedure that could detect oil-based contaminants in seafood in just 24 hours. The time saved by using the new test enabled FDA and state authorities to safely reopen the Gulf for fishing weeks sooner than would have been possible using the existing test. This meant seafood harvesters could go back to work sooner and consumers could again safely enjoy seafood from the Gulf.
   
• Infectious diseases—including those that could occur from hostile attempts to harm Americans—can take many forms and present FDA with serious challenges. FDA’s Center for Biologics Evaluation and Research has been studying potential hazards that range from smallpox and influenza epidemics to anthrax attacks and radiation poisoning. 
  
  
  FDA is tackling these threats through research and collaboration focused on medical countermeasures. For example, the agency has worked with the Centers for Disease Control and Prevention and industry to help manufacturers develop tests to prevent transfusions of blood and transplantation of organs infected by the West Nile virus. FDA’s work was critical in facilitating rapid development and deployment of these tests. Other major objectives of FDA’s regulatory science research include:
  
  
  1. The development of technologies to accelerate the large-scale manufacture of new influenza vaccines.
  2. Creation and evaluation of rapid testing methods for the detection of infectious microorganisms in such biological products as blood and tissue.
  3. Finding new methods to improve the shelf-life and stability of products that have to be warehoused for use in an emergency.
  4. Formulating new ways, such as needle-free systems, for more rapid use and self-administration of drugs.

Other priority areas include improving the design of clinical trials and manufacturing processes.

Advances in these areas will bring more innovative medical products to the market to help people with chronic and life-threatening diseases. I think that’s where the consumer would really appreciate or feel the investments that are made in this area.

Tecfidera approved for Multiple Sclerosis

About Multiple Sclerosis:

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function (relapses) are initially followed by recovery periods (remissions). Over time, recovery periods may be incomplete, leading to progressive decline in function and increased disability. MS patients often experience muscle weakness and difficulty with coordination and balance. Most people experience their first symptoms of MS between the ages of 20 and 40.

 

Treatment:

No drug provides a cure for multiple sclerosis so it is important to have a variety of treatment options available for patients, said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. Multiple sclerosis can impair movement, sensation, and thinking and have a profound impact on a person’s quality of life.

 

Tecfidera:

Results from two clinical trials showed that those taking Tecfidera had fewer MS relapses compared to people taking an inactive pill (placebo). One of the trials showed that those taking Tecfidera experienced a worsening of disability less often than patients taking a placebo.  

Tecfidera may decrease a person’s white blood cell count (lymphocytes). Lymphocytes help protect the body from infection and low counts can raise the risk of infection, although no significant increase in infections was seen in patients taking Tecfidera in clinical trials. Before starting treatment, and annually thereafter, the FDA recommends that the patient’s white blood cell count be assessed by their health care provider.

 

Flushing (warmth and redness) and stomach problems (nausea, vomiting, and diarrhea) were the most common adverse reactions reported by patients receiving Tecfidera in clinical trials, especially at the start of therapy. These side effects may decrease over time.

Manufacturer:

 

Tecfidera is made by Biogen Idec, Weston, Mass.

Reference:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345528.htm

 

CRO Leadership Awards' 2013

Every year, Companies achieving top 20 percentile perception scores in the areas of Innovation, Productivity, Quality, Regulatory, and Reliability were recognized for their achievement. 
These categories were defined for the CRO's as follows:

1. Innovation
2. Productivity
3. Quality
4. Regulatory
5. Reliability

Life Science Leader’s readership of pharmaceutical and biopharmaceutical executives have revealed about their struggles in efficiently vetting potential CRO partners. In response to this input, Life Science Leader developed the CRO Leadership Awards based on the industry leading research conducted by Nice Insight. 

The awards incorporate the common filters used by pharma companies to vet CROs with the added filter of peer feedback. This will help pharma companies focus on potential CRO partners who can handle their projects and are considered reputable in the industry.

The CRO Leadership Awards are based on industry research conducted by Nice Insight. Nice Insight offers intelligence reports to give clients a clear understanding of how their industry perceives their business, and a much more informed basis for strategic decision‐making. Nice Insight combines surveying of thousands of industry executives with other key analyses to serve both partnering groups and facilitate better overall outsourcing collaborations.

Unlike other industry awards which are given based on a subjective voting or nomination process, the only votes that count towards the CRO Leadership Awards are those of the pharmaceutical and biopharmaceutical companies using CRO services. 

Reference:

http://www.croleadershipawards.com/index.php/winners

Drug Labelling

FDA Aims to Help Drugmakers Update Labeling Format

The FDA is seeking stakeholder feedback on a proposed initiative that would encourage drugmakers to use an updated drug labeling format even if they are not legally required to do so. The Prescription Drug Labeling Improvement and Enhancement Initiative and an associated pilot project would ask applicants with NDAs, BLAs or efficacy supplements (ESs) approved before June 30, 2001, and ANDAs for which the reference drug has been withdrawn for reasons other than safety or effectiveness to voluntarily convert their labeling to the “Physician Labeling Rule” (PLR) format and submit it for approval. The FDA intends to identify and prioritize certain drugs and drug classes for label conversion based on public health impact.

Washington Drug Letter

Reference:

http://www.fdanews.com/newsletter/article?issueId=16575&articleId=153378

Implant for Genetic eye disease

Retinitis Pigmentosa (RP) is a rare genetic eye condition that damages the light-sensitive cells that line the retina. In a healthy eye, these cells change light rays into electrical impulses and send them through the optic nerve to the area of the brain that assembles the impulses into an image. In people with RP, the light-sensitive cells slowly degenerate resulting in gradual loss of side vision and night vision, and later of central vision. The condition can lead to blindness.

FDA approved the Argus II Retinal Prosthesis System, the first implanted device to treat adult patients with advanced retinitis pigmentosa (RP). The device, which includes a small video camera, transmitter mounted on a pair of eyeglasses, video processing unit (VPU) and an implanted retinal prosthesis (artificial retina), replaces the function of degenerated cells in the retina (a membrane inside the eye) and may improve a patient’s ability to perceive images and movement. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the retinal prosthesis.    

 This new surgically implanted assistive device provides an option for patients who have lost their sight to RP – for whom there have been no FDA-approved treatments. The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities.

The Argus II system is intended for use in adults, age 25 years or older, with severe to profound RP who have bare light perception (can perceive light, but not the direction from which it is coming) or no light perception in both eyes, evidence of intact inner layer retina function, and a previous history of the ability to see forms. Patients must also be willing and able to receive the recommended post-implant clinical follow-up, device fitting, and visual rehabilitation. 

In addition to a small video camera and transmitter mounted on the glasses, the Argus II Retinal Prosthesis System has a portable video processing unit (VPU) and an array of electrodes that are implanted onto the patient’s retina. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the electrodes. The electrodes transform the data into electrical impulses that stimulate the retina to produce images. While the Argus II Retinal Prosthesis System will not restore vision to patients, it may allow them to detect light and dark in the environment, aiding them in identifying the location or movement of objects or people.

The FDA approved the Argus II Retinal Prosthesis System as a humanitarian use device, an approval pathway limited to those devices that treat or diagnose fewer than 4,000 people in the United States each year. To obtain approval for humanitarian use, a company must demonstrate a reasonable assurance that the device is safe and that its probable benefit outweighs the risk of illness or injury. The company also must show that there is no comparable device available to treat or diagnose the disease or condition. 

The FDA reviewed data that included a clinical study of 30 study participants with RP who received the Argus II Retinal Prosthesis System. Investigators monitored participants for adverse events related to the device or to the implant surgery and regularly assessed their vision for at least two years after receiving the implant.

Results from the clinical study show that most participants were able to perform basic activities better with the Argus II Retinal Prosthesis System than without it. Some of the activities tested included locating and touching a square on a white field; detecting the direction of a motion; recognizing large letters, words, or sentences; detecting street curbs; walking on a sidewalk without stepping off; and matching black, grey and white socks.

Following the implant surgery, 19 of the 30 study patients experienced no adverse events related to the device or the surgery. Eleven study subjects experienced a total of 23 serious adverse events, which included erosion of the conjunctiva (the clear covering of the eyeball), dehiscence (splitting open of a wound along the surgical suture), retinal detachment, inflammation, and hypotony (low intraocular pressure). 

Three government organizations provided support for the development of the Argus II. The Department of Energy, National Eye Institute at the National Institutes of Health and the National Science Foundation collaborated to provide grant funding totaling more than $100 million, support for material design and other basic research for the project.

Stivarga - GI Tumour

FDA approves Stivarga for advanced gastrointestinal stromal tumors.

GIST is a tumor in which cancerous cells form in the tissues of the gastrointestinal tract, part of the body’s digestive system. According to the National Cancer Institute, an estimated 3,300 to 6,000 new cases of GIST occur yearly in the United States, most often in older adults.

The U.S. Food and Drug Administration today expanded the approved use of Stivarga (regorafenib) to treat patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease.

Stivarga, a multi-kinase inhibitor, blocks several enzymes that promote cancer growth. With this new approval, Stivarga is intended to be used in patients whose GIST cancer cannot be removed by surgery or has spread to other parts of the body (metastatic) and is no longer responding to Gleevec (imatinib) and Sutent (sunitinib), two other FDA-approved drugs to treat GIST.

Stivarga is the third drug approved by the FDA to treat gastrointestinal stromal tumors. It provides an important new treatment option for patients with GIST in which other approved drugs are no longer effective.

Stivarga was reviewed under the FDA’s priority review program, which provides an expedited six-month review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. The drug was also granted orphan product designation because it is intended to treat a rare disease.

The safety and effectiveness of Stivarga for this use were evaluated in a clinical study of 199 patients with GIST that could not be surgically removed and progressed after treatment with Gleevec or Sutent. Patients were randomly assigned to receive either Stivarga or a placebo. All patients also received optimal supportive care, which includes treatments to help manage side effects and symptoms of cancer.

Patients in the study took Stivarga or placebo until either the cancer progressed or the side effects became unacceptable. Results showed patients who took Stivarga had a delay in tumor growth (progression-free survival) that was, on average, 3.9 months later than patients who were given placebo. Patients who received the placebo were given the opportunity to switch to Stivarga when their cancer progressed.

The most common side effects reported in patients treated with Stivarga were weakness and fatigue, hand-foot syndrome (also called palmar-plantar erythrodysesthesia), diarrhea, loss of appetite, high blood pressure, mouth sores, infection, changes in voice volume or quality, pain, weight loss, stomach pain, rash, fever and nausea.

Serious side effects, which occurred in less than one percent of patients, were liver damage, severe bleeding, blistering and peeling of skin, very high blood pressures requiring emergency treatment, heart attacks and perforations (holes) in the intestines.

Stivarga was approved in September 2012 to treat colorectal cancer and it is marketed by Bayer HealthCare Pharmaceuticals. 

Reference:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340958.htm

Working for a CRO's

What is it feels like to work in a CRO and how to start a career in this booming industry. The article in the web link shares us the most exciting views on this industry. With an average growth rate of 7% in R&D positions in CRO, seems to be a major player in bringing the drugs / life saving pharmaceutical products for the betterment of the society. Experts and well experience Professionals in this field share their views and experiences on the clinical research industry. 


CRO one acronym with two meanings ?

Contract research organizations and clinical research organizations share an acronym; sometimes the names are even used interchangeably. Whether this is one kind of company or two depends on whom we talk to.

While contract research organizations can span the entire pharma pipeline from drug discovery to clinical trials and beyond, a clinical research company mostly manages clinical trials. People in the R&D business often consider clinical research management companies a subset of the broader CRO category. 

But those in the medical and public health sector tend to consider clinical research organizations their own species, unrelated to CROs that focus on bench work. That’s something to bear in mind when applying for a CRO job: Make sure we research prospective companies well so we know what kind of company we're talking to.

Reference:

http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2012_05_25/caredit.a1200059

Clinical Trial Process

Drug Development Process:

Following figure shows the outline of the Drug development process during the various phases of Clinical Trials.

Cancer - Generic Drug -Approved by FDA

FDA approval of generic version of cancer drug Doxil is expected to help resolve shortage. FDA has approved its first generic version of the cancer drug Doxil (doxorubicin hydrochloride liposome injection). Doxil is currently on the FDA’s drug shortage list. For products on the shortage list, the FDA’s Office of Generic Drugs is using a priority review system to expedite the review of generic applications to help alleviate shortages.

The agency is committed to doing everything we can to address drug shortages so that patients can get the medicines they need when they need them. During the past year, FDA has been working to ensure that supplies of doxorubicin HCl liposome injection were not interrupted. Generic drugs approved by the FDA have the same high quality and strength as brand-name drugs. The generic manufacturing and packaging sites pass the same quality standards as those of brand-name drugs.

Manufacturer of Doxil : Sun Pharma Global FZE (Sun)

Mode of Administration of the drug: Doxil injection is administered intravenously by a health care professional.

Concentration: 20 milligram and 50 milligram vials.

In order to compensate the shortage of Doxil injection, FDA announced that it would exercise enforcement discretion for temporary controlled importation of Lipodox, an alternative of Doxil produced both by Sun and Caraco Pharmaceutical Laboratories Ltd, which is not approved in USA. Enforcement discretion was also used to release one lot of Janssen’s Doxil made under an unapproved manufacturing process.

For the present time, FDA intends to continue exercising enforcement discretion for importation of Lipodox, and limited supplies of Doxil are available. Once supplies of Sun’s generic doxorubicin hydrochloride liposome injection are sufficient to meet projected demand, FDA expects to stop exercising enforcement discretion for any unapproved doxorubicin HCl liposomal product.


Reference:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm337872.htm

IEC - Redefining benefits to Subjects - India

Ethics Committee - Redefining compensation benefits to the Individuals in case of SAE (Serious Adverse Events)

In India, Pharmaceutical companies conducting clinical trial of drugs in India will no longer be able to get away with meagre and arbitrary payment of compensation in case of injury or death of subjects participating in such trials. 

For the first time in the medical history in the country, the Government has notified rules for grant of compensation in case of Serious Adverse Events (SAEs) like death and injuries on account of participation in clinical trial of drugs including biologicals and medical devices. 

There were no compensation provisions so far under the Drugs and Cosmetics Rules which govern approval of clinical trials by the Government. 

Compensation would now be awarded within three months of the reporting of injury or death. In the past five years, 2,242 people have died during drug trials in India, with an average compensation being awarded per death being a meagre Rs 2.2 lakh as per Health Ministry data. 

"With the notification of procedures of compensation, the Government has ensured the safety and rights of subjects participating in clinical trials. Henceforth all trials will be monitored at all the stages," a senior Ministry officer said. 

Drug Controller General of India, the apex drug regulator, will be the final authority for deciding the causes of injuries or death in clinical trials and also approving the final compensation amount in each case. Categories for grant of compensation have also been fixed depending on death, severe injury and minor injury and minimum compensation amount would soon be notified. 

So far, Ethics Committees set up by the sponsors of clinical trials, have been deciding the amount of compensation to be awarded in case of drug trial related injury or death. 

The amount would often be very low, a fact also pointed out by the parliamentary standing committee on health in its report on drug trials. 

According to the new notification, Ethics Committee of the medical institute conducting the trial, the sponsor of trial and its principal investigator will have to report the injury or death within 24 hours and submit their separate reports to the independent expert committee set up by the DCGI to review the case. 

The DCGI would recommend the final payment based on the independent probe panel's report, thus ruling out bias and unfairness.

Reference:
Economictimes.inditatimes.com