With the most comprehensive survey of clinical success rates across the drug industry to date1 suggesting productivity may be even lower than previous estimates, and other sources quoting failure rates at over 90% for Alzheimer’s drug trials, it is easy find fault with the current clinical trials model. Yet viewed from another angle, the approval rate for new molecular entities and drug applications filed with the FDA has remained fairly constant over the decade,2 so the industry must be doing something right.
The drugs being developed today are targeting many of the least understood, most difficult to treat diseases
The drugs being developed today are targeting many of the least understood, most difficult to treat diseases. Many such drugs are often aimed at older patients, already undergoing several treatment regimes for multiple and complex diseases – diabetes, heart disease, cancer and Alzheimer’s, making end points difficult to achieve.
Some industry estimates suggest that clinical trials account for 40% of overall drug research costs and those costs are rising. A report from market research company Visiongain predicts that the world market for pharma clinical trial services will be worth US$30.6bn in 2015.3 But with fewer blockbuster drugs likely in the future, and growing price pressure from payers, it is important that pharma companies become more efficient and increase the success rate of clinical trials.
Recognising the difficulties, the regulatory authorities have tried to make the clinical trial and drug authorisation process more efficient. The European Medicines Agency (EMA) has streamlined the authorisation process so that all clinical trial applications in the EU will in future go through an EU portal with one application, regardless of the number of Member States in which the trial will take place.
Only time will tell if this level of disclosure improves drug industry performance
The EU Clinical Trials Regulation, now published in the Official Journal of the EU and expected to apply from 28 May 2016, also introduces the requirements for greater transparency. The EU clinical trials register run by EMA plans to make the summary results of clinical trials conducted in Europe publicly available and free to download, although EMA has now postponed formal adoption of the policy on publication of clinical trial data until October, pending further clarifications on wording and practical arrangements.
Only time will tell if this level of disclosure improves drug industry performance – however, the ability to download such data was something that some pharma companies had argued against. There are many who believe such full disclosure of data has drawbacks in terms of protecting patient data and intellectual property, and the potential for misinterpreting specific data or using it out of context.
Shortage of people
One of the major problems when conducting trials is the lack of professionals able to run them and a lack of suitable of patients to recruit. A whole host of web-based tools for streamlining patient recruitment for clinical drug trials have been introduced as a result. More pharmaceutical companies are realising the value of focusing trial activities around large hospital clusters where a large population of patients already exists. The global contract research organisation, Pharmaceutical Product Development (PPD), and one of the largest university hospitals in Europe, Charité–Universitätsmedizin Berlin, are the latest to collaborate with the aim of increasing the volume of clinical trials conducted in Germany. PPD hopes the collaboration will shorten study start-up times, maximise the number of patients recruited for clinical trials, generate better data and ensure all site staff members are trained as necessary for the conduct of clinical studies.
In the UK, the Department of Health is funding a Health Research Authority (HRA) business plan to deliver a single approval system for all health research studies in England. This means streamlining the complex process of clinical research studies: making the setting up of such studies faster and easier by reducing bureaucracy and duplication.
The FDA argues that pharma companies routinely exclude the sickest patients from studies, fearing complications they may suffer from the drug candidates
Against this backdrop of recruiting difficulties, the FDA is looking for clinical trials to include more patients with multiple chronic conditions, believing such patients are too frequently excluded from new drug studies. The FDA argues that pharma companies routinely exclude the sickest patients from studies, fearing complications they may suffer from the drug candidates, but, as a result, the studies don’t reflect the treatment’s real effect. To counter this, the FDA recently issued a memo to its new drug reviewers asking them to work with drug manufacturers to include a broader population in trials. There is also a move to learn more from patient feedback on trials.
In addition, the regulators are calling for more ‘risk-adapted approaches’ to management and monitoring of clinical trials4 and use of ‘adaptive designs’ that allow for evidence accrued throughout the course of an ongoing clinical trial to shape the trial. This has led companies such as CluePoints to introduce ‘intelligent risk-based’ monitoring platforms, said to enable sponsors to better determine the quality and integrity of their clinical trial data.
Other moves to improve drug assessments could involve the use of more ‘real world’ data. Not only are electronic collections of health information about individual patients or national populations more widely available and searchable, social and mobile media are also enabling new means of collecting and checking data. It has even been suggested that incidental comments on Twitter could be used for data on adverse reports on drugs – the flip side, however, is the potential for clinical trial patients who share experiences on social media to ‘unblind’ clinical trials.
As data banks fill, organisations are seeking more efficient ways to accelerate and streamline data collection and management. Not surprisingly, the global clinical trial management system market, valued at $844m in 2013 is expected to grow at a CAGR of 14% from 2014 to 2019, to reach an estimated $1.85bn in value in 2019, according to a report on clinical trial management systems.5 The report also notes that the number of trials being carried out in the US and Western Europe has decreased, while more are being undertaken in regions such as Eastern Europe and Asia.
With the advent of personalised or stratified medicine, Big Pharma has had to be more collaborative and innovative in finding and trialling drugs. This has led to Cancer Research UK partnering with AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer. Over the course of the trial, up to 14 medicines in total from the companies involved may be tested at the same time, within one trial. Researchers will use the genetics of each lung tumour to identify small groups of patients who, because of the specific genetic changes causing their cancer, are more likely to benefit from a certain drug.
Medicines that show promise in the small groups of patients may be fast-tracked into larger trials involving more patients with the same genetic changes. New medicines may be added to the existing trial as new experimental treatments filter through from the lab. The move shifts the emphasis from designing trials around a specific drug, to designing them around selecting from a range of drugs for a specific patient.
References
1. M. Hay, DW Thomas, JL Craighead, C Economide and Jesse Rosenthal, Nature Biotechnology 32, 40-51 (2014). Published online 09.01.14
2. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm381397.htm
3. https://www.visiongain.com/Press_Release/344/'Pharma-clinical-trial-services-market-will-reach-30-6-billion-in-2015'-Predicts-new-Visiongain-report
4. FDA Guidance http://www.fda.gov/downloads/Drugs/.../Guidances/ UCM269919.pdf
5. www.transparencymarketresearch.com/clinical-trial-management-systems-market.html