The pivotal role of “big data” in understanding disease and new therapy development

The increasing use of clinical data is rapidly improving our understanding of many clinical conditions. By studying the natural history of disease progression and identifying objective disease biomarkers, we will move closer to identifying potential new treatments or develop a targeted strategy for the use of existing therapies in patient subgroups in order to obtain maximal benefit.

Our understanding of the value of “big data” in the development of new disease treatments has evolved significantly in the recent past with the development of combined data sets to ultimately improve patient outcomes in clinical practice and new drug development. Two years ago I, in collaboration with a number of colleagues, identified both the need and potential for such an approach to gain a greater understanding of Parkinson’s disease (PD). Other diseases have undergone efforts to standardise and integrate relevant data, which have advanced therapeutic trial designs and enabled model-based drug development and personalised medicine strategies.

A number of data sharing models had already been developed which could provide a model for the sharing of PD data

  • The Alzheimer’s Disease Neuroinaging Initiative (ADNI)
  • The UK Medical Research Council Dementia Platform (DPUK)
  • The European Medical Information Framework (EMIF)
  • Sage Bionetworks DREAM Data Challenge

A meeting was organised by Parkinson’s UK in collaboration with the Critical Path Institute to bring together all of the key players in the field . These included academic and clinical researchers, industry representatives, government agencies and regulatory authorities and resulted in a summary publication.

The first aim of the meeting was to identify the key gaps that existed in PD research. These included:

  • The need for regulatory approved endpoints, trial designs, and modeling tools
  • Identification of early diagnostic tools to maximize the impact of neuromodulatory therapies
  • Development of reliable biomarkers to monitor disease progression, particularly to assess agents that may modify the course of the disease
  • Understanding disease subtypes to enable the stratification of patients to allow for more efficient clinical trials and the development of a personalized medicine therapeutic strategy.

With these in mind, the meeting focused on the information that would be required to address these questions and in particular how the existing clinical data could be integrated into a combined platform to allow for a precompetitive data-sharing approach. This would allow the key questions to be addressed while reducing duplication and increasing the ultimate effectiveness of clinical research.

There are many different PD clinical datasets in a variety of formats and the challenge is to identify the key common data elements that can be combined in order to address the key questions that had been identified. The key questions to be addressed are:

  • Data transferability
  • Remote data accessibility
  • Privacy and consent issues
  • Data remapping to agreed standards
  • Data integration

But there are also challenges to data sharing including:

  • Different data formats
  • The need for reliable longitudinal (rather than single point) data
  • Access to datasets
  • Data protection and “ownership”, with particular reference to patient approval
  • Incentives and recognition for the researchers who have generated the data
  • The development of integrated infrastructures that will allow for the ready access of data
  • The cost of the maintenance and updating of a common data source
  • An understanding of new sources of data such as the use of remote monitoring devices

While these are not insurmountable, all of the potential barriers need to be highlighted and an appropriate strategy put into place. This will ensure that any initiatives will allow for the maximum benefit of the data sharing and that obstacles will be identified, wherever possible, in advance.

But we need to remember that the key stakeholder group in such a project is the patients. Informal discussions that I had with people with PD suggested that the vast majority were happy for their clinical data to be made available under certain conditions – primarily that it would be in an anonymous format and that it would be available for research free of charge. Their view was that, although it may not be of direct benefit to them, it will help to develop new therapies that will impact on future generations of people with PD. In particular, we will get to the stage where the treatments address the condition rather than the symptoms, as at present. But in order to achieve this, we need a much better understanding of the condition and the identification of biomarkers to objectively monitor the progression of the condition. The public view on data accessibility is also highlighted in the AllTrials campaign which seeks openness in the availability of clinical trial data to allow for an objective understanding of data obtained from drug trials. People who have participated in clinical trials would expect no less.

A plan is now being developed to establish a global database for PD. Specifically, it will require:

  • Identification of the key current databases
  • Agreement on data standards and common data elements
  • Establishment of guidelines for data sharing
  • Engagement of all stakeholders

Finally, patient datasets and registries are also being considered in the context of the future clinical trial development to maximise the benefit of patient datasets. The European Medicines Agency has established a Cross-Committee working group on patient registries. This will evaluate the potential use of existing and planned patient registries in the design of clinical trials. This will be a key step forward and it will provide yet another benefit for patients from the data that has been collected.

Posted in clinical trials, Research | Tagged , , , , , , | Leave a comment

Potential earlier access to new medicines?

The Prime Minister published a “Strategy for Life Sciences” in 2011 and one of the recommendations was to investigate the potential of making new drugs available to patients at the earliest possible opportunity. An expert working group was set up to investigate this and to make recommendations on how it could be implemented. This was led by the MHRA with representatives of the pharmaceutical industry, relevant government departments and research-funding charities. I was appointed as a member of the working group to represent Parkinson’s UK.  After a number of meetings, a report was published a couple of weeks ago which has now been submitted to the Government.

There are two main recommendations. The first was the launch of an Early Access to Medicines Scheme. This would be of particular importance for promising unlicensed medicines which are deemed to be safe and efficacious and which would address areas of “high unmet medical need”. This refers particularly to relatively rare conditions for which there are currently no treatments. Because of the library of drugs that is already available for the treatment of Parkinson’s, it’s unlikely that any new drugs would be covered by this programme.

The second recommendation was to develop an Adaptive Licensing Programme. This has already been proposed by the European Medicines Agency (EMA) and guidelines are being prepared. Essentially, medicines which have been shown to be safe and effective in early phase III multi-centre trials would be made available on prescription for people not in the study, but these people would be monitored closely for safety issues such as adverse effects of the drugs. It is likely that such an initiative will come from the EMA as the centralised licensing authority and this will then be implemented in member states (by the MHRA in the UK). It was considered that the existing legislation is sufficiently flexible for such a scheme to be implemented without legislative changes.

There are some examples already available of products which have been fast-tracked through the regulatory process. These are primarily for the treatment of medical conditions that are considered as being sufficiently rare that it would not be possible to access a large enough body of patients to carry out a normal clinical trial. 37 such therapies have been licensed within the EU since 2001. However, some companies said that they were unaware of such a programme, so a further recommendation from the working group was to publicise this pathway more widely within the pharmaceutical industry. There was also the suggestion that industry and the regulatory bodies should consult at an earlier stage to work together on medicine development. This would be of particular importance for novel therapies such as cell and tissue transplants.

So where do we go from here? The report has been submitted to the Government, so we will eagerly await the results. However, as there is a similar initiative planned by the EMA, the Government may be tempted to wait for Europe to take the lead. This is despite the fact that no new legislation would be required to implement the schemes in the UK. We shall await the results eagerly.

Posted in Research | Leave a comment

Emerging therapies for CNS diseases

I recently attended a conference which focussed on the development of new drugs for conditions such as Parkinson's and other neurodegenerative conditions. This included both the biotechnology and pharmaceutical industries as well as external funders such as Parkinson's UK.

A number of interesting themes emerged. Firstly, despite rumours to the contrary, the pharmaceutical industry remains committed to the area of neurodegenerative conditions such as Alzheimer's and Parkinson's. This is despite reports of a significant downsizing of the number of researches employed by the companies in this area. This is due to the emergence of a new strategy for drug development. In the past, the pharmaceutical industry would fund all stages from pre-clinical trials through early clinical trials to the marketing of the drug. This has now changed and the pharmaceutical industry now only gets involved in the process at a much later stage.

So initial research, such as the identification of drug targets or the screening of chemical compounds, usually takes place in academia or in small biotechnology companies. The lead compounds are then brought forward to the pre-clinical stage before initial phase I clinical studies to determine the drug's safety profile. All of this is likely to be carried out by small companies or in academia. There is an increasing trend for research funding organisations such as Parkinson's UK to support research within this space.

Once there is evidence that the drug is safe, and initial phase II "proof of concept" studies have taken place - does the drug have any clinical benefit - the pharma companies may be interested in purchasing the rights to the drug and then invest in the costly phase III multi-centre clinical trials. This provides a return on investment for the smaller companies while the larger pharma companies don't have to take the risk of investment in the early stages of drug development.

This may appear to be a a logical progression and in a lot of cases, it works. However, it is dependent on the ability of the smaller biotech companies to identify what targets and chemical compounds will be of interest for the pharma industry who will ultimately be purchasing the rights to the drug. The companies also carry out an assessment of the market. At the moment, there are over 20 drugs to treat the symptoms of Parkinson's with only four for Alzheimer's. And in the UK, there are 450,000 people with Alzheimer's and 127,000 with Parkinson's. So it's not difficult to work out where the priority is. Another area of interest is conditions where there are no therapies available such as Huntington's or MND.

From a Parkinson's perspective, while we would like to see investment going into the development of drugs which will treat the condition rather than the symptoms. However, the clinical efficacy of such drugs would be extremely difficult to measure, especially considering that people are likely to remain on their symptomatic medication while being treated with the drug that modify the progression of the condition. We also know that the placebo effect has a significant role in Parkinson's. So, based on clinical tests, it will be very difficult to differentiate between symptomatic and disease-modifying effects. For this, we need reliable biomarkers which can be quantified and provide an indication of the progression of the death of nerve cells. The "Tracking Parkinson's" study will provide us with a vast amount of information that may help us to identify such biomarkers.

So, despite the apparent lack of progress in this area, there is still cause for optimism. Funders such as Parkinson's UK can play a key role, by supporting early-stage research to understand the basis of the condition, the identification of biomarkers as well as campaigning for a continues investment in the area.

Posted in Research | Leave a comment

Increase in animal research – what does it mean?

Last week, it was announced that the number of animals used in medical research in the UK in 2012 had increased by 8%. This comes at a time when there is a lot of pressure on researchers to actually decrease the use of in vivo studies that are carried out and to move towards the use of alternatives. In particular, we are actively promoting the 3Rs – to reduce, refine and replace the use of animals in medicine.  However, a detailed analysis of the figures showed that the primary reason for the increase was the use of genetically-modified animals, particularly rodents.


Conditions such as Parkinson’s are extremely complex and while we can use model systems, such as nerve cells grown in a dish, to study the condition, we need to remember that the brain is three dimensional and that there are many different types of cells. Looking at one type alone will only provide us with a certain amount of information but if we are to really understand – and move closer to a cure for – conditions such as Parkinson’s, we then need to study the whole brain. We also need to consider the fact that other parts of the body may also be affected by the condition.


In order to study what happens in the brains of people with Parkinson’s, we need a good model system. In the past couple of years, we have made great strides in our understanding of the condition. In particular, the genome-wide association studies (GWAS) identified genes that may increase the risk of developing Parkinson’s. We also know about external factors such as organophosphate pesticides. So we can put these together. We manipulate the animal’s genetic makeup and treat them with low doses of pesticides. We are now developing models where nerve cells die in specific areas of the brain in a similar manner to those observed in Parkinson’s. This means that, for the first time, we can screen for drugs that may slow down, halt or even reverse the progression of the condition.


Many researchers are using subtle differences in their approach in order to determine what will be the best model. When this has been agreed, we expect to see a decrease in the number of animals used as rather than trying to develop the best model, we will be able to use one. This will bring us closer to a cure.

Posted in Research | Leave a comment

Vitamin D and Parkinson’s

A recent report has suggested that vitamin D may have a neuroprotective effect for people with Parkinson’s and taking vitamin D dietary supplements may slow down the progression of the condition. The study compared the development of Parkinson’s symptoms between a group who had received a vitamin D3 supplement and an untreated group. The study showed that people who took the vitamin supplement had a slower rate of symptom progression. However, the researchers said that they couldn’t discount the fact that this was a general effect of the vitamin supplement on ageing and age-related changes in muscle and bone rather than being a Parkinson’s specific effect.

However, previous studies have suggested that people with Parkinson’s may have lower vitamin D level than people without the condition and are more susceptible to develop conditions such as osteoporosis. This may help to explain why additional vitamin D supplements may appear be of benefit for people with Parkinson’s as they would bring levels back to normal.

This study underlines the importance of diet for conditions such as Parkinson’s and how something as simple as ensuring correct vitamin levels can make a big difference to your health. But it may not be necessary to take vitamin supplements as a balanced diet is also likely to give you the recommended daily amount. So it’s important to consult a dietician. They will assess your diet as well as well as advising on any additional supplements that you may need. In most cases, a modification of diet is usually sufficient. You can find out more from the Parkinson’s UK information booklet which gives advice about various aspects of diet for people with Parkinson’s.

Posted in Research | Tagged , , , , | Leave a comment