Beyond paper based PRO and now.. even beyond ePRO

Why should a sponsor look beyond ePRO?

It is a known fact that it take huge amount of capital, usually in billions of dollars to conduct and finally launch a dug into the market. It is also known that there are several studies that are either terminated or stopped half way due to several reasons technical and non-technical associated with it resulting in wastage of time and money both. Patient related data capture during a clinical trial plays an important role in the making of a drug. Through out the different phases of clinical trials information from patients are taken for efficacy, BA, BE measurements and make a considerable part of the trials or study. A lot of sponsors have been using ePRO to collect patient reported outcome, still makes only 30-40 % of studies being conducted using EDC and further less using ePRO.

It is time that sponsors look at more cost effective ways to gather PRO from subjects under trials and keep abreast with the pace of developing technologies. The next big wave in capturing PRO for clinical trials is the use of mobile phones and I am sure there are many a company that are working on it. Mobile phones are going to be the next computers that would enable users to manage all their communication and information transfer over mobile phones.

What can a sponsor look at from a mobile phone based PRO?

Well there are quite a few things for a Sponsor or for that matter a CRO to be looking at, when it comes to mobile based PRO system.

1. Faster reported outcome
2. Compliant to international regulatory bodies
3. Cost effective
4. Patient safety
5. Logistically simpler
6. Less erroneous data
7. Data integrity and security
8. New and improved features
9. An information management system that allows sponsors CROs to have instant access and action at different stages of the trial.

PRO as it is called - The Patient reported outcome may be defined is a questionnaire used in a clinical trial or a clinical setting, where the responses are collected directly from the patient. Typically in a clinical trial, when the drug is manufactured, the pharmaceutical company needs to test the drug at various stages and levels on patients or other wise called ‘subjects’. As the drug is tested over the different phases of the clinical trial on the patients, there is continuous testing that goes on at the back-end – done by the clinical research team. Every patient who is screened in for a particular trial and given their dozes, needs to comply to the medication guidelines prescribed by the investigator by taking the medication on time and then filling up a questionnaire – This questionnaire is called the PRO – The patient reported outcome that the patient needs to fill as mentioned by the investigator. – Well, I am not talking too much in detail in this blog, but will certainly elucidate on the different stake holders, terminologies and processes that go in while a clinical trial in is process –

As mentioned above the PRO that is usually a paper questionnaire comes with several questions ranging between a few to many- some times about 70- 100 questions. Well, it would be incorrect to state that these are the right numbers as the number of questions in a PRO may differ – case to case , Study to study.
A PRO (patient reported outcome) is usually used to assess a patient’s in any one of the following constructs:
1. Symptoms (impairments)
2. Functioning (disability)
3. Health related quality of life (HRQOL)
4. Quality of life questionnaires (QOLs)

A few examples of the types of PRO may be given below:
SF-12(Health Survey), SF-36 (Health Survey), Adult Asthma Quality of Life Questionnaire (AQLQ), Migraine Specific QOL (MSQOL).

You can check out about PRO related QOLs online, people have posted many sample questionnaires. EX: http://www.nephrology.rei.edu/SF36.pdf


Most often there is a little confusion when people talk about Patient reported outcomes and Patient based outcomes – There is a slight yet large difference in the two terms that is usually used in the clinical trials industry.

Patient PRO - Implies only that the patient provides the information. This information may, or may not, be of concern to the patient.

Patient Based Outcome – A patient based outcome implies that questionnaire covers issues of specific concern to the patient.

Clinical Trials - Yet another part of mHEALTH

Clinical Trials may be defined as voluntary research studies, conducted in people, that are designed to answer specific questions about the safety and/or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments. (Courtesy: FDA). Clinical trials have been existent since eleventh century wherein the learned lot of those times tried, tested and laid regulations for experimental use and testing of drugs and other related substances. Today in the 21st century, we have a whole population across the globe working on prevention and cure of diseases with latest technologies and science in a regulated environment put down by governing authorities and bodies like FDA, HIPPA, CDISC and others.

Clinical Trials can be classified into:
1. Observational Study
2. Interventional Study

There are different types of Clinical Trials specified by US NIH (National Institute of Health) as:

1. Prevention trials: look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.
2. Screening trials: test the best way to detect certain diseases or health conditions.
3. Diagnostic trials: conducted to find better tests or procedures for diagnosing a particular disease or condition.
4. Treatment trials: test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
5. Quality of life trials: explore ways to improve comfort and the quality of life for individuals with a chronic illness (a.k.a. Supportive Care trials).
6. Compassionate use trials: provide experimental therapeutics prior to final FDA approval to patients whose options with other remedies have been unsuccessful. Usually, case by case approval must be granted by the FDA for such exceptions.

The clinical trials process may be categorized into four major phases namely:
1. Phase I - Phase I trials are the first stage of testing in human subjects.
2. Phase II- Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered not to work as planned, or to have toxic effects.
3. Phase III -Here studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is.
4. Phase IV - Phase IV trial is also known as Post Marketing Surveillance Trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold.

Well, this is just a brief overview of what can be a Clinical Trial. It would come as an astonishing fact to those who are looking at it for the first time... This industry is typically conservative and a lot of people do not know what actually goes behind the scenes while making a drug. This industry is regulated by major regulatory and compliance authorities. There are a lot of other interesting things that make this a booming sector - EDC - Electronic Data Capture, ePRO- Electronic PRO, mPRO- Mobile PRO, about which I shall discuss in my forthcoming blogs.

Happy reading !! :)