gr-cis.com

In 2011, Mary Elizabeth Williams was diagnosed with metastatic melanoma, a finding that usually means a patient has six to seven months to live. Knowing melanoma doesn’t respond well to traditional cancer treatments, she decided to take a chance on a phase I immunotherapy trial of a new drug. Williams wrote about her experience in her book, A Series of Catastrophes and Miracles: A True Story of Love, Science and Cancer. It was a journey, she says, from last resort to hope and possibilities.

Lindsay McNair, chief medical officer of WCG, spoke with Williams in a webinar last week, discussing the patient perspective on clinical trials, what they do right and how to change what they do wrong.

Q: Given your options — treatment that didn’t offer a good success rate, death or participating in a clinical trial — do you feel that you were well informed on your options and what participation in a clinical trial entailed?

A: At the time, Yervoy (ipilumumab) was a very new drug on the market and had a 30 percent success rate. It’s scary embarking on a course of treatment for which there is very little precedent. There were not a lot of human subjects who had come before me, and I knew that the risks could be great. There was a risk, not only of it not working, but of dying from the treatment, which did happen to some people on this trial. I had great conversations with the immuno-oncology team and they were very clear about why I would be right for this trial. It was a choice that was made, not just based on the drug and the cancer, but very much on the patient. And that was a turning point for me — that I was being listened to and that I was going to be collaborating with a group of people who believed in me as a patient.

Q: When you were approached about the trial — the informed consent process — what was the hardest thing for you to understand as people started to talk to you about what the trial entailed, etc.?

A: My understanding of clinical trials was limited, and my understanding of immunotherapy was nil. I had a lot of questions and concerns and there was a lot for me to process. My oncologist did the best she could in terms of explaining treatment. My initial conversation with the immunotherapy team at Memorial Sloane Kettering was the first time that I really felt that maybe I wasn’t going to die. That maybe treatment in a clinical trial would work, but with the understanding that maybe it wouldn’t. I was in a state of desperate, deep panic. I had a conversation with someone who said that maybe participating in a clinical trial didn’t have to be a last resort for me. Maybe it could be my first resort. And that really changed the game for me.

Q: How much of your information and your understanding about what the study would entail for you came from the process, this conversation you had with study team members as opposed to literally reading the paper document that you were handed?

A: I had an initial meeting with a nurse. I was handed the document, and we sat down together and the expectation was that I would sign it on the spot. Even though we went through the document thoroughly, I remember feeling that I would have to sign the document whether I fully understood it or not. I also recognize that there were a lot of things that just couldn’t have been understood at that time because it was such a process and a new form of treatment, but I am really struck with how vulnerable I was, how much I didn’t know and that there was such an expectation of me. And I don’t know, in retrospect, if there was a lot of understanding by the study team that I was not fully competent. I wasn’t. I was a complete mess — physically, mentally, emotionally. These decisions often need to be made under very difficult circumstances, quickly, and you do the best you can with the timeframe that you have. But I recognize now how hobbled I really was. And I don’t think that is unusual.

Q: How do you believe that the informed consent form and process in a phase I trial should talk about the possibility of benefits? How should we express the truth about the odds of success in a very early study, which are low, but still leave people with hope? How can we balance that?

A: That’s a very difficult question especially because in phase I trials, there is not a whole lot of expectation of success. My consent form was pretty clear about that. I felt that I had an understanding that there was a hope of success. But at that point, we were not talking about the word cure. There was no evidence of possibility that I would have all of my disease eradicated. It was really just about efficacy and potential tumor reduction. That is what was communicated to me. And the bar was set low. And my expectations were reasonable.

I’m grateful that the way it was communicated to me was, “We are going to try.” It was about time rather than about the disease. That is a smart way to approach it. Maybe this is about, “We can extend your life.” Because, ultimately, that’s really what we want. I would be happy to live with tumors if it meant I would live longer. That’s what I think most people approaching cancer now are really looking at management. So, I think that’s fine to communicate it that way.

For the rest of the interview, please go to WCG’s website: https://bit.ly/2U9qzqu.

Two kinds of data integrity problems cast shade on research results and erode trust in scientific inquiry: questionable research practices and flat-out misconduct, a data integrity expert says. And while intentional misdeeds can result in regulatory, or even criminal, action, both categories can cause irreparable damage to clinical trials, companies and individuals.

Most data integrity problems in research fall into the questionable practices category and are not due to intentional acts, said Donna Kessler, research integrity officer at Duke University, during a recent CenterWatch webinar. They result from professionals who take shortcuts, rush research or just make bad decisions.

Questionable research practices (QRP) are generally understood across the research community and include failure to properly cite sources and methods, sloppy or incomplete documentation of results or, most commonly, failure to retain data and results.

Intentional misconduct, however, is defined by regulators. Researchers who fabricate data, falsify existing data or plagiarize the work of others can be subject to legal penalties and or debarment from participating in government-funded research.

Misconduct and questionable practices across the spectrum are more prevalent than some think, Kessler said, citing research that found 2 percent to 3 percent of researchers admit to fabricating or falsifying data, 14 percent have observed a colleague falsifying or fabricating data, and 33.7 percent admit to using QRPs. More than 70 percent observed others committing QRPs, Kessler added.

Research misconduct can be a result of bad judgment, lack of training or poor oversight, she said. In other cases, misconduct stems from competition for funding and recognition, or a sense of entitlement.

Researcher Eric T. Poehlman, for example, served a year in prison and was barred from getting any additional federal grants after he falsified data in 17 NIH grant applications and 10 of his papers. He later said he was motivated by his desire to advance as a respected scientist. He felt his area of study was important enough to warrant what he considered “minor” misconduct.

The repercussions of QRPs and misconduct are many, Kessler said. They can not only skew results and erode public trust, they can do serious clinical harm, as well.

In one of the most notorious and harmful cases of research misconduct, British surgeon and medical researcher Andrew Wakefield in 1999 published a paper claiming a link between childhood vaccines and autism. Not only did he falsify his data, his sample size was only 12 children, and he did not have ethics board approval for the study.

Wakefield was ultimately barred from practicing medicine and the study was retracted, but the ripple effects and the debate over childhood vaccines continues. Vaccination rates dropped globally thanks in part to intense press coverage of the Wakefield study. Further studies have shown there is no link between vaccines and autism.

Both the Wakefield and Poehlman cases and others show the potential long-term effects of misconduct on public health and the harm it can do to the credibility of researchers and scientific knowledge, Kessler stressed.

Not all data integrity issues are covered in federal regulations, and Kessler stressed that researchers and institutions must go further to protect the reliability and validity of research results. “The regulations are really the floor; they’re the starting point. To have integrity in research, you have to go beyond the regulations,” she said.

You can’t really prevent wrongdoing if a researcher is bent on misconduct, Kessler said. But researchers and institutions can step in when problems are caused by lack of training, sloppy methods or bad judgment, especially if the problems are caught early in the research process.

You also can prevent intentional misconduct by providing integrity education and training, reviewing and improving research and data practices, and encouraging reporting and investigation of possible misconduct.

To encourage integrity review, Kessler said, make reporting easy, with anonymous or online reporting options, stand firm against retaliation and take credible allegations seriously. Organizations also can implement tools for mentors and trainees, such as plagiarism detection software.

“Raising awareness of these types of wrongdoing is helpful, but you have to have some more active programs and changes in order to create a culture and a climate where integrity is at the forefront,” Kessler said.

To listen to the webinar, go here: https://bit.ly/2V2m8uR.

In 2014, The Tufts Center for the Study of Drug Development estimated the cost of bringing a drug to market to be $2.6 billion.¹ With such escalating costs and drug pricing discussions at an all-time high, many companies are exploring ways to continue to innovate and bring novel drugs to patients while reducing the overall costs of drug development process. Enter… remote clinical trials.

Sometimes known as digital or virtual trials, remote clinical trials are a distinct sign of the times we live in and the future we are marching toward. With the digital age as its guide and patient-centricity at its core, the remote clinical trial model aims to accomplish better results (and less costly ones) through a significantly reduced number of investigator sites, the use of digital apps and equipment, remote monitoring, and protocol requirements that center around the patients and their homes. But in addition to the patient-centric aspect and the competitive advantages that remote trials offer, such as efficiency and speed, do these trials also present cost saving opportunities, or can additional costs be expected? While virtually (no pun intended) every aspect of a clinical trial is impacted when going from a traditional to a remote model, in this article we will explore some of the main categories where we already see cost savings and potential cost challenges. Let’s first look at some of the main areas that offer opportunities for cost savings.

Saving Costs Through Remote Trials

Investigator Fees

With investigator fees responsible for about 40 to 60 percent of a total clinical trial budget, it is no surprise that when this cost category is impacted, it brings significant change to the bottom line. While various investigator fee subcategories are impacted due to the nature of remote trials, some of the top ones are derived from the actual number of investigator sites involved in these trials, costs for patient visits (procedures and staff costs), and other site costs (i.e., start-up fees, pharmacy fees, overhead costs, other administrative fees, etc.).

For example, remote trials will not require what we sometimes refer to as the traditional brick-and-mortar setup of multiple study sites. Instead, by using technology to reach and engage the patient directly throughout the trial, remote clinical trials use fewer physical sites, requiring fewer investigators. Some trials may only have a few, or even just one central site coordinating patient involvement in the trial. Although site staff will still be required to a certain degree, the number of actual sites participating is significantly less than in traditional trials. The sheer reduction in the number of investigator sites is one of the biggest, if not the biggest, driver of cost savings when conducting remote clinical trials.

Another example in this category is the reduction in patient visits and site costs. Remote clinical trials look to also streamline protocol visit procedures and requirements in addition to many of the procedures being conducted directly by the patient alone without the need for oversight by site staff. This has a direct impact on costs for site staff time and effort and overhead associated with such procedures. Additionally, with the elimination or at least significant decrease of traditional on-site patient visits, associated site fees costs that are currently covered by many sponsors are reduced, even for central coordinating sites participating. You can read a previous article on this specific topic here.

Site Monitoring And Site Management

Monitoring is another very costly aspect of clinical trials, with on-site monitoring making up around 25 to 30 percent of the overall cost of clinical trials.² As a direct result of drastically reducing the number of investigator sites, traditional on-site monitoring and management costs are also reduced. Additionally, remote site monitoring is likely used, which further reduces the need for site monitors and all the travel, hourly rates, and expenses associated with this type of personnel.

Patient Travel Costs

Patient travel is a cost that is significantly reduced with remote trials due to the simple fact that most of the protocol visits take place in or around the patient’s home. This is not only helpful to the bottom line but also for the convenience of the patient and is especially helpful for patient populations for whom travel is challenging.

Patient Recruitment And Retention

While not a cost savings at the level of the previous categories, patient recruitment and retention are areas where many sponsors may see some cost savings, especially if they have not already been utilizing digital means for these activities in their traditional trials. Social media and other digital efforts drive patient recruitment and retention strategies in remote clinical trials and have innately lower investment costs. Retention is also expected to be greater for these trials, as many of the barriers to patient participation, such as travel to the investigator site, are eliminated. This in turn reduces the cost of having to recruit new patients to the trial, although this piece is still something to keep an eye on.

Potential Cost Challenges

It is important to note that despite the cost savings associated with remote trials, there are also potential cost challenges. Let’s look at some of these…

Harmonizing Platform

The first area to consider when thinking about potential cost challenges in remote trials is the investment in a technology platform to harmonize all the different digital efforts in the trial. From patient wearables and apps, to data from local labs and data at central coordinating sites, there is a fundamental need to make sure all the data is harmonized for analysis, monitoring, cleaning, and eventual submission. While likely one of the biggest costs associated with remote trials, it is imperative that the right platform and partner are used to pull everything together. The ROI on this expenditure will only be seen over time and with the scaling of these types of trials for the sponsoring company.

Patient Equipment

One forgotten area of cost is the equipment the patients will use for remote trials. With a traditional trial, sponsors are accustomed to having investigator sites that own standard equipment for standard visit procedures. This is different for remote clinical trials, as the patients are essentially performing most of the study visit procedures themselves in their homes. When the strategy is laid out for these trials, the costs for any equipment, app, wearable, service, or other items that will be needed at or near the patient’s home in order to accomplish the protocol requirements must be considered.

Learning Curve Associated Costs

As these trials are relatively new to our industry, there is a natural learning curve and thus associated costs with it. For example, there may be a need for additional training of all stakeholders, additional personnel time across the different vendors, sponsors, coordinating sites, patients and ancillary staff, or even the additional costs associated with a major failure of an early clinical trial in this space. This is a cost that companies considering embracing this model need to anticipate, at least for the near future.

Commercial Impact of Reduced Physician Involvement

Although sometimes forgotten in the clinical development stage, from a commercial perspective, it is very important that physicians remain engaged throughout the drug development process, even within remote clinical trials where the number of investigator sites and, as a result, the number of physicians are drastically reduced. If physicians do not feel involved throughout the clinical development process, they may not feel comfortable enough with what they know about the drug itself to recommend it to their patients once the drug goes to market.³ This is something that, if not well-planned by study sponsors, may have a negative budgetary impact post-approval.

Conclusion

Although the mentioned cost observations showcase the current state of remote clinical trials, it is important to note that such trials are relatively new to our industry. Lessons are being learned and things are constantly changing, as would be expected in our digital age. These trials should not be thought of as something that will necessarily decrease costs in and of themselves, simply because remote clinical trials should cost less. Rather, it is the scaling of such trials over time that has the greatest potential for cost savings and opportunities. Lastly, due to the fluidity of the topic, there is a good chance that new costs, of which we are not yet aware, may arise. But I guess that is the beauty of diving into an exciting and new way of doing something – there is great potential for risks and amazing rewards with it.

In this age of smart phones, cloud-based voice helpers and all things “Google” the public and medical profession have many ways to find a clinical trial. The most comprehensive listing of clinical trials in the world can be found at www.clinicaltrials.gov but when you get to that site it’s often difficult to navigate and understand, even for those of us in the research field and biopharmaceutical industry. Imagine a patient or caregiver who has received an unexpected diagnosis and is searching for information.  “Frustrating,” “confusing” and “not helpful” may best describe their first impression.

To be most patient centered, researchers and industry must consider the how and where information is available for clinical trials and treatments. It’s important to provide high quality information in a way that can be easily understood while helping to direct patients and their caregivers to centers of excellence for additional consultation.  If we don’t take the lead for our areas of interest, some other information source will likely fill the void.

Important Considerations for Clinical Trial Awareness:

• Each of our organizations should consider  a “wiki” page for the compound or treatment being investigated. Is someone in your organization monitoring associated and relevant Wikipedia content?
• If “newly diagnosed xyz” is searched, what is the search result? Where does that information lead the searcher? Is the information helpful/harmful?
• How buried is the trial in the www.clinicaltrial.gov  ocean of information? Would you or your family be able to navigate to the right information to find a center of excellence or an expert?
• Would your trial benefit from a stand-alone digital presence? Would a social media presence be helpful? Knowing how often the public is searching for information for patients seeking treatments or trials in a specific disease area provides good insight into whether or not a digital presence is important to patients and caregivers.

These questions are relevant and timely for researchers and industry. Enrolling clinical trials is time intensive and costly, speeding or slowing new treatments being researched to potentially be available to help more patients. The more transparent clinical trial information is to patients and their families, the more informed questions they can ask their healthcare providers.

There are many ways to find medical information, but they are not all equal. We place great trust in our medical professionals to give us the best information, but they cannot be expected to keep track of every new biomarker and treatment option being investigated. They too turn to “Google” hoping to find updated and understandable information to share with patients. We should always consider how best to help provide good information to the medical community in the forums they are using! It’s likely they might say be the one asking, “Hey Alexa, find me a clinical trial…..”

Clinical research associate (CRA) turnover has long been a complex and challenging issue. We can recruit more CRAs, increase publicity in colleges, and introduce assessment standards. I could quote various statistics regarding turnover, but I won’t. This article is not about those things. This article is first in a four-part series that will look at how employers can make effective changes in the workplace that will empower both line managers and CRAs to take control of their own mental health resilience in light of their demanding role. A happier CRA is more likely to stay with an employer and will lead to greater productivity, resulting in better efficiencies within our clinical trials. To quote the renowned American thought leader on positivity psychology, Shawn Achor, “The greatest competitive advantage in the modern economy is a positive and engaged brain.”¹

This article is the first of a four-part series that will investigate the disillusionment CRAs today experience with their role, why they do, and what we can do about it. I conducted a survey completed by 700+ CRAs, so let me start by explaining why I did.

An Inherently Stressful Lifestyle

The idea for this article came when I read a book by Stephen Ilardi, “The Depression Cure: The 6-Step Program to Beat Depression without Drugs.”² I read this book because I have severe depression, and when you have depression you try to “fix yourself,” so you read a lot of self-help books. Due to my background in sciences and clinical research experience, the book made me think about how vulnerable CRAs are to developing mental health issues in the working environment.

The book outlines six key lifestyle elements that can protect against depression by reducing your stress-response-circuit activity. By reducing your “runaway” neurological stress response, you increase your resilience to depression and anxiety.

So, taking it back to the daily role of a traveling CRA, how are they at risk? Let’s briefly look at the six lifestyle elements researched by Ilardi:

1. Exercise – This tricks your stress response into down-regulation. CRAs have a sedentary lifestyle due to office work and traveling. Reduced exercise does not lower stress hormones, so the body can remain in a fight-or-flight status.
2. Natural sunlight exposure – Natural daylight is 100 times more powerful than indoor artificial lighting. The lighting levels have a direct impact on stress hormones and levels of vitamin D, and low levels of Vitamin D have been found in people with depression. Sunlight exposure allows our bodies to convert cholesterol into vitamin D3. CRAs monitoring inside, working in offices, and on transport may not get enough natural sunlight, so they are potentially at risk.
3. Restorative sleep pattern – This is required for processing of neurochemicals accumulated in the day. CRAs’ sleep patterns can be affected by travel, staying in hotels, and workload. This was mentioned by some CRAs who completed the survey I conducted.
4. Social connectedness – Brain activity is regulated by social connections. Periods of isolation can up-regulate stress hormones. CRAs who often work in isolation, are home-based, and travel have reduced social connectedness.
5. Value-related activity – This is engaging activity related to your own personal values. If work takes precedent and you are unable to construct a meaningful work/life balance around your values, your stress response will increase.
6. Omega-3 fatty acids – Studies indicate these help regulate brain function more effectively. Our bodies cannot make omega-3 fatty acids, and our diets do not provide the optimal omega-3 to omega-6 ratio necessary for antidepressant effects. The ratio should be 1:1 Omg3:Omg6. In the average diet, it is now 16:1, and this can affect a person’s stress-response resilience. CRAs may not be any more at risk of this than the average person; however, a CRA’s food choices may be limited when traveling, working late at the office, and monitoring on-site.

I remember what it was like to be that typically tired CRA — traveling on my own somewhere strange; tired; checking into a hotel room late at night; searching for some high-calorie, high-sugar processed snack in my bag; powering up my device to do some work (when it is already 11 p.m. and I need to be on-site at 9 the next morning).

The CRA Role — Then And Now

I was that CRA 15 to 20 years ago, and my on-site monitoring day looked like this:

• Review hard copy medical patient notes and source data, including patient diaries and questionnaires.
• Review the hard copy case report form and perform a source data verification check, noting any monitoring discrepancies.
• Visit the pharmacy, and conduct drug accountability. Return to the clinic for a short meeting with the site staff, hopefully the investigator! Go home; write the visit report and follow-up letter the next day. No mobile phones, no technology.

Nowadays, we may expect to see this type of daily routine:

• all of the above tasks, although now working on much more complex, higher-risk trials involving biological agents, rare orphan diseases, and advanced technology
• managing constant information notifications via mobile phones and other devices, i.e., we don’t stop working
• conducting teleconferences on the road
• more guidelines and documents to review in line with the risk-based approach
• perceived organizational and cultural expectations that multitasking and extreme busyness are now the norm and to be expected
• being out of the office for an increased number of days at a time (on-site visits).

I am not suggesting CRAs 15 or 20 years ago had it easier or harder than CRAs today. I am saying recent developments in the way employees work and the technology that has since developed are not conducive to good mental health, i.e., never completely switching off from work and increased expectations of multitasking. However, each trial is unique and affected by factors such as study training, user-friendly guidance documents, a good team structure with clear line-of-sight objectives, and feeling supported by management.

The Relationship Between Mental Health And Burnout

After reading the book, I was interested in how CRAs manage their mental health in line with their day-to-day roles. So, I conducted an anonymous survey with nine questions, the results of which will be revealed in the subsequent parts of this series. The survey was distributed via several forums, such as The Association of Clinical Research Professionals, Clinical Leader, a clinical research group on Facebook, LinkedIn CRA-specific groups, and my personal connections.

I vastly underestimated the huge response to this survey — over 700 responders from many different countries and organizations. There were no monetary incentives, just the chance for CRAs to provide their own perspectives and ideas.

For the majority, this survey provided an outlet for current difficulties our CRAs face in their day-to-day lives. It also prompted some strong feelings about what mental health actually is, e.g., a few responders were very unhappy I asked about mental health, as they feel it is a private matter and not related to burnout. I believe chronic stress can result in burnout and if burnout is left untreated, it can lead to a decline in your mental health.

What is burnout? Here is an explanation from Robert Ballard, head of the American Psychological Association’s Psychologically Healthy Workplace Program:³

“Burnout is an extended period of time where someone experiences exhaustion and a lack of interest in things, resulting in a decline in their job performance. A lot of burnout really has to do with experiencing chronic stress. In those situations, the demands being placed on you exceed the resources you have available to deal with the stressors.”

According to the World Health Organisation,⁴ overall health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. This definition was established in 1948 and has remained unchanged since. I believe any individual’s mental health is always in a fluid state, moving along a continuum.

So, where do you think a CRA should be on this continuum?

The answer is anywhere. No one “should” be in any particular zone at any dictated time. Where you are depends on you as an individual, your coping resources, and your external environment.

Figure 1: Mental Health Continuum Model

It is important to recognize that someone with a diagnosed mental health condition can be in the healthy green zone, and someone who has not been diagnosed with any mental health conditions and was in the green zone two weeks ago can be in the orange or red zone now, perhaps due to a house move or database lock.

A 2013 National Survey⁶ found one in five Americans lives with mental illness. And, according to a U.K. survey conducted in 2017,⁷ three out every five employees (60 percent) experienced mental health issues in the preceding year because of work. Just 13 percent felt able to disclose a mental health issue to their line manager. Those who do open up put themselves at risk of serious repercussions. Of employees who disclosed a mental health issue, 15 percent were subject to disciplinary procedures, demotion, or dismissal. This also came up in the CRA Burnout survey.

As the statistics above show, there is much stigma surrounding mental health. Even more so in the clinical research industry, where importance is placed on being a productive, professional academic working to high standards within regulations, usually on a tight timeline.

In part two, we will reveal what CRAs had to say about their jobs and their mental health. We will look at the answers to questions such as:

If you have depression and/or anxiety, have you been able to inform your employer and/or your line manager? Have you ever left a CRA role because you were concerned your mental health would deteriorate?

Stay tuned.

Contract research services are now the largest single cost category in pharma R&D spending, accounting for almost $90 billion last year, according to Tufts Center for the Study of Drug Development.

All in, CROs raked in about $33 billion last year for services including project management, trial monitoring, biostatistics, site management and medical writing — an increase of 12 percent from 2017, Tufts researchers found.

And it looks like sponsors are getting their money’s worth in terms of development speed. Sponsors that used CROs with established relationships with sites shaved 39 days off study initiation compared to sponsors that retain control. And CROs working with sites for the first time got studies started 77 days faster, on average. Time to build and release a database was 21 days faster when handled by CROs.

This kind of acceleration in trial timelines may be a factor in recent increases in drug development. The number of active drugs in worldwide research or development has risen steadily from almost 8,000 between 2007 and 2010, to nearly 11,000 between 2015 and 2018. There were nearly 3,500 companies with at least one drug in the development pipeline over the same period, a dramatic increase from the 2,000 companies between 2007 and 2010, Tufts found.

CRO advocates were cheered by the results of Tufts’ study. “The report clearly shows that clinical research and technology companies get you there faster,” said Matt Feldman, spokesman for the Association of Clinical Research Organizations. “Whether it’s risk-based monitoring (RBM) or decentralized trials, CROs are continuing to innovate and drive improvements in the drug development process in ways that are valuable to sponsors.”

Still, sponsors aren’t completely on board with the outsourcing model. Few companies reported using contract researchers in any kind of systematic way and only one-third of drug sponsors surveyed reported feeling satisfied that outsourced oversight processes are well established. Fewer than one-fifth of the drug companies, in fact, rated these processes “highly effective.”

The outsourcing rush also has led to more concentration in the CRO market, Tufts found. The 10 largest CROs controlled 57 percent of the money spent on outsourcing in 2018, a 12 percent increase in the past seven years.

Niche, or specialty, CROs have seen strong growth — about 10 percent per year — but medium-sized companies have grown only about four percent per year since 2011, Tufts researchers found.

But it’s not clear that outsourcing has cut drug development costs, which have continued to rise between six percent and seven percent per year. Tufts has previously reported that the average drug costs $2.6 billion to bring to market.