Clinical Intelligence Analytics - Growth Trends

Trial Growth Trends Dashboard

Growth Trends Dashboard provides insights into the growth trends of clinical trials over a period of time. This helps us gauge how the industry is growing. 

Below (Figure 2.1) is a snapshot of the dashboard without any data filters. Figure 2.2 is another representation to view the Year over Year growth. Year 2019 is the current year and hence the decline should not be viewed as negative growth. We still have few months remaining in 2019.

Figure 2.1

Figure 2.2

The Dashboard has the same summary tiles on top of the dashboard except a new metric to measure average number of days from registration to study initiation or enrollment. The average for prospectively registered studies is 107 days, which means that it takes 107 days on an average for a study to enroll its first patient after it has been registered.

Broadly, there are 4 times that are important milestones from study registration to the posting of results. The trends in this dashboard shows these 4 important milestones. The Growth Trends Dashboard can answer some of the following questions:
1. How the study registration in the US has grown over the last 20 years?
Registering the study is the first step and hence, it helps us in understanding how the industry is growing. A decline in study registration would mean less successful drugs or devices reaching the market. With patented drugs losing patent protection, a declining product pipeline can negatively impact the growth of the industry. CRO(Clinical Research Organisations) conduct the clinical trials on behalf of the sponsors and hence a decline in study registration can put brakes on the growth of CRO industry.
The study registration trend is increasing consistently except in year 2005 and 2008 that saw a sudden jump. International Committee of Medical journal Editors(ICMJE) began requiring trial registration as a condition of publication in September 2005. This explains the jump in 2005. The jump in year 2008 could be related to the recession period.
Beyond 2008, there has been consistent growth sometimes in double digits. The outlook for the industry as a whole looks positive.

2. Has the growth in the studies initiated been consistent?
Sponsors take lot's of efforts in initiating a study. It's a commitment they make in terms of money and efforts and hence it is an important indicator to see the growth in study initiation. The average duration for a study to go from registration to initiation is 326 days.
The growth in number of studies initiated over the last 20 years is also consistent until 2016. The growth has declined in last 2 years around -6.5% YOY. Year 2019 may also end up following the declining trend. The rate of YOY growth has consistently gone down from 42% in 2002 to -6.5% in 2018. If the trend continues, the coming years may prove to be difficult for the industry and companies need to start looking at alternatives to increase the product pipeline.
3. Are studies being completed growing consistently?
Completing the study is like clearing a big hurdle in drug development. Conducting a study is lengthy, costly, complex and risky and hence a successful completion is a big milestone and a big relief to sponsors.
The growth in studies completed over the last 20 years has been positive and consistent until last year 2018 when the growth was negative. The rate of growth declined consistently after 2007 with a recovery in 2014. The rate of growth came down to 1% in 2017 and then dropped to -8.5% in 2018. The current year 2019 doesn't look to be making any recovery. With just few months remaining, 2019 is 64% away from last year 2018. 
4. Are sponsors submitting study results growing?
ClinicalTrials.gov launched the results database in September 2008 and hence sponsors started posting the results after that. 
The trend shows that the posted results increased at a very high rate until 2014 recovering 39% in 2017 but again declined 20% in 2018. Current year 2019 seems to be matching up but it is yet to be seen if it will end with a positive growth.
If you notice, I compared the current year 2019 with last year 2018 to get an understanding of the current year performance. I did get some fair idea but I wanted to go one level down and see the current year has performed on a quarterly and monthly basis as compared to the last year. I wanted to see if there is any trend where there is high activity in certain months, so I created a dashboard which can provide some insights into understanding the current year performance in Figure 2.3.

Figure 2.3

The four tabular reports on the top row compares the monthly comparisons of current year months with previous year months. The increase column is the difference and appear in green or red based on whether the change is positive or negative. The bar charts on the bottom row compares the same metrics on quarter basis. Remember, August is the current month and hence the third quarter will not have complete values.
Let's take a look at all 4 metrics one by one and make some observations.
1. Study Submissions:
Current year has performed well so far and the number of studies have maintained a positive growth when compared with the same period of last year. Observe that last August had the highest number of studies submitted and unless there is a trend to submit the studies in the last few days of the month, we can expect August to play fairly well but may not be able to exceed. The lead current year has maintained in the first 2 quarters may help to gain a positive growth this year in number of studies submitted.
2. Studies Initiated:
So far, not a single month with a positive growth and the current year months have unperformed with a large margin. There are no months in the remaining period with unusually high or low activity and so if the trend continued, we may see a large drop in the 2019 study initiations as compared to 2018. I will keep an eye on that in the coming months and share with the readers here.
3. Studies Completed:
The monthly and quarterly numbers looks disappointing similar to study initiation. December month has high numbers possibly due to year end activities so we can expect some improvement in filling in the gap but the overall outlook doesn't look promising. 2019 may end up with a significant drop as compared to 2018.
4. Study postings:
The first two quarters have performed well and the current quarter also looking good. Hopefully, 2019 would see some positive growth. 
With that positive note, see you till next time. 

Clinical Intelligence Analytics - Summary

Clinical Summary Dashboard

Summary Dashboard gives an overall picture of clinical trials in a summarized form at a high level. 

Below (Figure 1.1) is a picture of the dashboard without any data filters. If I make any selection or filter, I will call it out and mention it.

Figure 1.1

The Dashboard tries to answer some basic questions to start with, and then we start looking at things from different angles and dimensions. 

The summary Dashboard can answer some of the following questions:

1. How many studies have been registered so far in the US?

This the total number of studies registered in the database. As on 09-Aug-2019, there are 313,345 studies registered in the US.

2. How many studies did actually started?

A study is considered to be started when it enrolls its first patient. It's an important milestone in the entire clinical trial process. 291,364 out of 313,345 which is around 93% of the studies did actually start by enrolling a patient.

3. How many studies did actually completed? 

Another important milestone is when a study completes and the patients who participated in the study stops receiving the drug. Of the 291,364 studies that started, 167,511 studies were completed, which is 58%. 

4. For how many studies did the sponsors posted the results?

Once the study is completed, the data collected is analyzed and the results are posted. Results Database was initiated in 2008 whereas the study registration began in 2000, so there might be studies without posted results. 38,127 studies have results posted out of 167,511 completed studies which is 23%.    

5. How many studies are currently recruiting patients?

A study recruits patients as study facility location called study sites. These study locations could be in many countries. 54,968 studies are presently enrolling patients including the ones that are enrolling only by invitation. This means 19% studies of the 291,365 studies that were started are still recruiting patients. 

6. How many patients were recruited in the past?

There were few enrollment values such as 99999999 that were converted to 0. About 490 Million people participated in the clinical trials across the globe from 210 countries. As per the recent United Nations estimate, the would population is 7.7 billion. We can say that 6.4% of world population has participated in clinical trials of the US. Other countries may have their own clinical trials registry.

7. What is the average duration of study completion?

Duration is the difference in the start and completion date of the study. 2.62 years is the average duration for a study to complete. Phase 3 trials are large scale studies and takes longer than phase 1 and 2, but we will look at that later. We can say that it will take around 8 years for a new drug to complete all the phases of clinical trials before it can apply to FDA for approval. Add another year or 2 for pre-clinical testing of the drug on laboratory animals. Now I understand how lengthy, complex and risky is the entire process of drug development. I will not go into the drug pricing strategies but you got a sense why those drugs are so un-affordable, even with insurance sometimes.

8. How many total sponsors registered the studies?

28,068 sponsors from both industry and non-industry (government agencies etc) have registered studies. We will see the ratio and proportions later.

9. What share of registered studies were interventional or observational?

Almost 80% of the studies are interventional studies where some kind of therapy is given to the participant.

10. What percentage of registered studies were sponsored by industry and non-industry sponsor?

Non-Industry sponsors leads with 3/4th of studies sponsored by them.

11. Top 10 sponsors who registered the most studies?

GSK is the leader. Pfizer and Astrazeneca are other sponsors from pharmaceutical industry following with a close margin. National Cancer Institute, a non-industry sponsor, is at a second position. 

12. What are the top medical conditions for which the studies were registered?

Surprised to see obesity at number 2. Asthma and depression are in top 10. I never thought they were so important but I guess our lifestyle changes are responsible for their growth. Breast cancer is the most studied medical condition.

13. What is percentage share by the overall status of the study?

Only a small portion of the studies were withdrawn and suspended, however, 5.65% studies were terminated which could be a cause of concern.

14. What are the top 10 countries that recruited the patients?

US has recruited about 18% of the total participants. 

Taiwan at no 2 surprised me. I found it enrolled around 67 million participants for an observational study but Taiwan's total population is around 25 million. The enrollment number is an outlier to me, however, I did not change it. Cambodia too has a study that enrolled 15 million participants for an observational patient registry sponsored by non-industry sponsor French National Institute. 

Since observational studies enroll large population of participants, let's look at who are the top countries who recruited for interventional studies only (Figure 1.2). Almost 82 million participants have been enrolled so far and US once again leads the chart with a contribution of little over 13% and China closing the gap at second position.   

Figure 1.2

You can always slice and dice the analysis to look at things from different perspective in a dashboard. It's real fun to create your own questions in your mind and then try to find out the answers yourself.

See you till next time.

Clinical Intelligence Analytics - Insights

Clinical Trial studies a new drug or device before it is brought to the market. The new therapy is tested on human subjects to evaluate its safety and efficacy.
Sponsors or investigators of certain clinical trials are required by U.S. law to register their trials on and submit summary results to ClinicalTrials.gov website. 
While working for a CRO as a Business Intelligence and Data warehouse Engineer, I gained some basic knowledge about the Clinical Research. I got so much interested that I decided to study Bio-sciences Management and Analytics subjects in my graduate MBA program. Unfortunately, my curiosity and the desire to learn more about Bio-sciences did not end there. 
I am passionate about creating insights out of data and I always try to unravel the layers of my curiosity by diving deep into the data. So, I decided to get the data from ClinicalTrials.gov and create Clinical Intelligence Analytics for myself. Here is the link in case you want to download it too.: https://aact.ctti-clinicaltrials.org/
The objective of creating this application is to share the insights with the community so that they know more about the things happening in this space. I would be really happy if this application could be of any benefit to patients, physicians,sponsors and other partners of the ecosystem. There are few online websites that helps patients find the recruiting study. However, I did not find any easy way that can help patients find out more about particular studies or sponsors or investigators in the past so that they can make informed decisions.
I used Talend software to get the data and used Qlikview BI to do data preparation and to create analytic dashboards. I have created more than a dozen dashboards so far and creating more as we go along. 
I would appreciate to leave a comment if you read the posts and find it useful. 
Since I do not want to make the posts boring for readers by putting a lot of information in one single post, I would be posting multiple posts in a series in coming days and update the link below in this post.

1. Clinical Summary Dashboard
2. Growth Trends Dashboard

Here are few links that would help in understanding basic terminology and basic information on ClinicalTrials.gov:
Common Terms
Trends Charts

Blockchain for Healthcare and Clinical Trials

Blockchain for Healthcare and Clinical Trials by Manohar Rana

The article is based on our 3rd place winner's proof of concept presented at Generation Blockchain Challenge.

          In general, healthcare and clinical trials are complex business environments mainly due to its direct impact on the human lives and various regulations built around them. There are various stakeholders in the entire ecosystem, and the need to improve on how these stakeholders collaborate and communicate with each other is ever increasing. Technological advancements from time to time have made significant improvements, but due to slow adoption of these technological advancements in healthcare in general, there is a great potential for newer technologies like blockchain to bring significant improvements in the overall systems.
          Healthcare organizations have made significant improvements through technological and process innovations that have benefitted and improved the entire customer experience. The most important customer in the ecosystem is a patient, and the entire healthcare business is centered around this customer. The ultimate aim of the various players like physicians, clinics/hospitals, pharmacies, drug manufacturers (pharmaceutical companies) is to bring value to a patient and enhance the overall customer experience. Then there are regulatory bodies like Food and Drug Administration (FDA), that oversees all these players, ensure the rights of a patient are protected and that they not misused in any way. A patient is the end consumer of the benefits in the entire value chain.
          On the other hand, in clinical trials, the drug manufacturer companies actually partners with human subjects aka patients to try their trial drugs on them before they bring the new drug to the market. Some of the key players in the clinical trials process are the Pharmaceutical company or the drug manufacturer, Contract Research Organisation (CRO) and Site Investigators (Physicians). Institutional Review Board (IRB) act as a regulatory body under the FDA. Since the other actors in the ecosystem are organizations that have their own technological infrastructure, the subjects remain at the receiving end. They have a limited role to play in the entire process and is limited by the technological capabilities of other's systems. Regulatory requirements make Organizations business systems slow, complex and inflexible. Generally, both healthcare and clinical trials partners have greater needs to collaborate and share the information through these complex systems.
          Attempts are made from time to time to come up with centralized systems that can facilitate greater collaboration and quick information sharing, but such systems pose their own challenges of ownership of data. Integrating data from different systems owned by different parties is a challenge. One alternative way could be to try to connect the trusted parties that are known to each other on a common platform. Blockchain technology has the potential to play that role. It may be too early to predict what role blockchain can play since there are not enough use cases that are being tried upon. It is difficult to say if Blockchain can displace the existing systems completely or complement them for some time before it actually does that. The objective here is not to speculate that possibility of whether Blockchain is a replacement for traditional Clinical Trial Management Systems but to explore the possibilities of small use cases that can actually bring value to the entire ecosystem.
     
Before we discuss how Blockchain can play an important role in clinical trials, it is important to understand the current challenges in the healthcare and clinical trials.

Few of the challenges in clinical trials are:

1. Subject Recruitment: To ask and convince a healthy subject to try a new trial drug is a challenge. There could be different motives for a healthy person to take that risk for monetary or personal reasons. Sponsor's find it very difficult to identify and recruit ideal subjects. A lot of times, the self-reported information provided by subjects cannot be authenticated leading to issues like dual enrollment, false disclosures, higher screen failures, a potential risk of severe adverse events (SAE's), and lawsuits leading to increased cost and bad quality of clinical research trial data.

2. Conducting trials: Sponsors make changes to the study protocols modifying inclusion and exclusion criteria mentioned in the study protocol after the study has started. At certain times the changes are genuine but sometimes the changes are made to widen the inclusion criteria or narrow down the exclusion criteria so that more subjects can be recruited easily.

3. Lack of trust and transparency.

4. Challenges in collaboration and communications.

Blockchain will increase and establish the trust in clinical research by the fact that tempering and manipulating the research data in blockchain is very difficult and easily traced. Self-reported data by the subjects generally lacks trust, which ultimately impacts the quality and cost of the drug trial. There is lack of trust in the way clinical research data is gathered, analyzed, and reported. Trust is further decreased because of unethical and unprofessional practices such as altering and not reporting the inclusion and exclusion criteria in a protocol to suit the interests of drug manufacturers. The timestamped block transactions can be easily traced and verified, making it less prone to manipulation and tempering. It would be worth reading the article about blockchain timestamped protocols here.

Blockchain will increase the transparency, collaboration, and communication in clinical trials. There are many partners in the clinical research ecosystem like Pharmaceutical companies(sponsors), CRO’s, study investigators (Physicians), hospitals, laboratories, insurance providers and patients, and there is a great need for all partners to collaborate and communicate effectively because human health is at stake.  The challenge is that every partner has their own technology systems which limit their ability to communicate effectively and efficiently. A lot of time and money is wasted in requesting, transferring, and communicating the information between different systems.
Blockchain brings all the trusted parties in the ecosystem to a common platform enabling them to see the clinical health records flowing through the system in real time and make timely decisions.
Not only that, Once the identity of a subject is established in the blockchain network, blockchain also addresses the issues related to subject’s dual enrollment in multiple studies at the same time saving the subject from being misused and exploitation. It is very difficult to find if a subject has enrolled in other studies. Ed Miseta, in his article, has highlighted the issue of dual enrollment in great detail here.
From sponsor’s perspective, it saves them lot of efforts wasted in subject recruitment causing higher screen failures.

Another important aspect of blockchain is that it enables a patient to play an important role as a participant. Currently, a subject is always at the receiving end of the value chain and has very limited or no access to his information. For example, in case of an adverse event, once a patient’s adverse event is notified to the physician, the patient has no idea how his case is followed up by a physician with other stakeholders. Blockchain system facilitates a patient to become an important participant in the whole ecosystem.

The inherent architecture and advantages of blockchain will make various processes and systems irrelevant and unnecessary, making the overall process of clinical research simple and cost-effective. The direct impact of this will be that it will help in bringing down the overall cost of bringing a new drug to the market, which ultimately will be passed on to the patients. More importantly, a subject would become a key participant in the clinical trial process and would be saved from misuse and exploitation.

Blockchain technology has the potential to bring disruptive changes in healthcare and clinical trials, that would make many of the current processes and businesses obsolete. It's in the best interest of the entire industry to explore the opportunities blockchain provides to remain sustainable in the longer run.

Tableau - Implementation Challenges and Best Practices

Hi All,

I thought of sharing my leanings and experiences with Tableau so far.

This post will describe some of the challenges you could face while implementing Tableau BI in your enterprise from architectural standpoint.

If you are evaluating BI tools or planning to start implementation, you will definitely benefit from this post. I would be highlighting some of the best practices that you can include in your list.

Tableau is flexible when it comes to playing with and analyzing your data. It gives you complete freedom to choose and connect to your data source, and quickly start building those nice Viz (reports or charts or dashboards).
You can do pretty much everything to join the data sources in a SQL, put filters to restrict your data. If you are a data analyst, you can build some really compelling data visualizations or charts in a very short span of time.
Now you show those nice visualizations with your team or department and they too get very exited.

Till here it was all cool stuff. The challenges starts from here.

1. Do I don't need a Datawarehouse star schemas.?
Datawarehouse star schema contains Fact and dimensions that gives you enormous benefits in simplifying your implementation. You won't believe how it can benefit in terms of performance, scalability and maintenance.
Some may argue that Tableau doesn't need any kind of warehouse or these fact and dimensions star schemas.
Well, if you are really a very small enterprise then you may not need it but otherwise if you have good amount of data and have various source systems and applications, then do not build your BI without a datawarehouse. Or sometimes, your organisation has a warehouse but as a data analyst you may be tempted to NOT use it.
Since Tableau does not have any centralized metadata layer, users are free to create their SQL the way they want. This freedom proves costlier in long term strategy.
Developers build their SQL's on top of OLTP or normalized data structures and the result is you have highly complex SQL's with large numbers of joins giving you poor performance.
Very soon you will have hundreds of those complex SQL's with lots of duplicate data/information where one SQL may differ from another SQL slightly. It's not so easy to debug those complex SQL's to make any additions or alterations. Now you understand how difficult it would be to maintain those SQL's.
Star schema reduces those joins and makes your SQL very simple, and of course the performance is way better.
Tableau can extract the data in extract mode and improves the performance to some extent but do not just ignore the other benefits.For some reason in future if you need to make your application in Live mode then you may need to completely redesign it. Such reasons could be more frequent data refresh or implementing row level security for which you need to have Live connection for your Tableau application.

2. Temptation to put ALMOST everything in one Tableau Workbook:
When you start creating an application, you start with small dataset providing answers to very limited or few business questions. This is what tableau is built for.

Slowly when more and more people starts looking at it, they start asking for more and more information. This is when we start adding new data sets, joins, transformations and conditions. And our application starts growing from all angles.
It becomes more complex, performance goes down and it becomes difficult to  scale.
If we take a break here and plan things, we can do it in much better way.
Once we realize that our application is growing, think of going to point no 1 above of creating/extending the dimensional model.
You need recreate your application using a dimensional model. If you think about this early, you will reduce the amount of rework you would have to do.
The ideal design would be to do all the data analysis/discovery using your source systems structures (assuming you do not have a warehouse or the required information is not present in a warehouse at all).
Utilize all the freedom Tableau provides here. But once you start thinking of making it available for mass consumption by enterprise users, design the required subject areas (Facts and dimensions) or extend the existing ones.
Build your application now using these subjects areas. Your application would be simple, fast, scalable and easy to maintain. Since the new SQL would be using less joins, fewer calculations and aggregations, it would be fast and easier to read.
You can now imagine the benefits. If you need more data elements or metrics, simply keep adding them to your subject areas.
This will enable you to extend or scale your application to a greater extent BUT this does not mean you can still put almost everything in one workbook.
Definitely there is some more work here but I am sure you would appreciate the benefits it would bring in the long run.

3. I Still want to put almost everything in one Workbook:
You may be wondering if I am against that. Well I am not.
There are many instances where we need to have information to be displayed on our dashboards side by side that may be coming from different subject areas or Stars but there are certain things we need to consider and remember.
Since Tableau does not have a Semantic layer (aka Common Enterprise Reporting Layer), we need to have all the tables added to that one workbook as Data sources.
Here the grain of the data plays an important role. If the grain of the data is same then all can fit in one data source/SQL.
But if the grain of the two data sources are different and there is a need to have an interaction between these data sources then the real trouble starts.
When I say interaction between these two data sources, I mean to say that we need to pass common filters between them or need to show the data coming from these two data sources into one Viz/report.
When we need to have an interaction, we need to have a join between these two data sources. Tableau allows joins across data sources or perform blending but it may prove to be very costly in terms of performance and stability.
You would be surprised that even if individual queries have sub second response time, after applying the join the response time may be in minutes.
If your individual queries have limited or small data, it may work for you in some cases.
Better always test it out. Even Tableau experts suggest to avoid using the blending.

4. OK. what is the Solution then:
I know its frustrating when we talk about limitations only. Here it is also important to understand why such limitations when Tableau is such a nice tool?.
Well, Tableau is a tool for data discovery. Quickly go grab your data and starts visualizing it. Maps are inbuilt and required no configuration like in many other tools. But once we have built those nice dashboards we need to make it available for the enterprise users. Tableau can do certain things here but its not made for that. Now you are trying to make it do something that some enterprise BI reporting tools such as Oracle OBIEE or Business Objects or Cognos are just made for that. These tools can do some data discovery but not the way Tableau does, similarly Tableau can do some dashboarding but not the way they do it.
Here I am not comparing Tableau with them since they are not comparable and have totally different use case and technologies.

5. What else can I do to?
All right. Here is the solution.
We need to design our Tableau workbooks and dashboards intelligently keeping in mind the limitations.
Think of having a common landing page workbook with hyperlinks to all the other applications. Think of having some very common filters on your landing page. So your first workbook have just dimension data for those filters.
Now you can also think of making one or more of these filters mandatory meaning users need to have a filter value selected in order to go to a specific workbook/dashboard.
This would help in cases when your workbooks/dashboards have tons of data and you want to avoid just showing all of that data and slow down your application.
Now, you can build your simplified workbooks based on individual common subject areas and link them to your landing page.
Since Tableau allows to pass the filters between workbooks, you can pass the common filters from one workbook to another.
There may be certain cases when we want to have a dashboard/report having data from 2 different data sources and in those cases you can consider blending. I know I said Tableau experts suggest to avoid it.
See if blending works fine for you else think of creating a physical table in database combining the two sets of data having different grains.
This table will have data at both the grains and some indicator column will tell the row has data for which grain. you will find any example on the web for such cases since this issue is not specific to Tableau but common to data warehouse.

6. THAT'S IT?
Well I guess So until something comes to my mind. Please post your comments and questions, and share your thoughts and experiences.

Thanks for reading.
Manohar Rana