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Patient Questionnaires in clinical trials: What are they and what are they used for?

Food and Drug Administration (FDA) defines a Patient-reported outcome (PRO) as any expression of the state of health made directly by patient without the response being interpreted by a doctor or anyone else. These PROs can encompass different types of measurements, depending on the clinical trial including symptoms, health status, participant satisfaction with the trial, treatment preference, etc. and are important in assessing a patients quality of life on a treatment.

There have been great advances in patient care over the years, with patients gaining more and more of a control in terms of their health and decision-making when it comes to selecting their treatments. PROs, are a great way to give patients a voice that can be captured in a structured way through validated questionnaires. This provides doctors with invaluable feedback to help them understand how their patients are tolerating a particular treatment.

What is a PRO or quality of life questionnaire like?

Specifically, PROs, can be in the form of a diary, scale, or questionnaire, and should provide some form of quantitative data. This type of numerical data, often in the form of a scaled rating system, allows investigators to track any changes in patient at any time during and after treatment and also helps to standardize answers so that they are not open to interpretation leading to bias in the assessment.

It is important for PROs to have instructions or guidelines so that it is completed correctly. They must have information about its validity, reliability and on how to interpret the data obtained, such as reference values ​​in populations.

What are the different types of PROs?

PROs can either be generic or specific.

Generic PROs are designed to be used with a wide range of populations and can cover a large number of measurements. There are numerous validated designs of this type of PRO. The EuroQol (EQ-5D) , is a commonly used PRO, which measures the general health status of any patient through 5 health dimensions (mobility, personal care, daily activity, pain/discomfort and anxiety/depression) with three severity levels (no issues, moderate issues, and severe issues). At the end of the questionnaire, there is an EVA (visual analogue scale), with a value from 0 to 100 to determine our general state of health.

There are already many questionnaires that have been developed and many questionnaire models can be modified. The specificity of the model can range from evaluating a symptom such as anemia (such as FACT-An ) to something a bit more general, such as the most widely used PRO for any type of cancer, the QLQ-C30 , developed by the European Platform for Cancer Research and Treatment (EORT), which assesses the quality of life of cancer patients through 30 questions divided into global health, functionality (physical, cognitive, emotional, social and daily activities) and symptoms (fatigue, pain, nausea, insomnia, etc.). They are evaluated using a scoring system from 1 (not at all) to 4 (very much), except for the last two questions, which deal with general health and quality of life and have a range from 1 (poor) to 7 (excellent).

There are also specific questionnaires that have been designed to assess a defined answered for a given pathology or a population group. There are a greater number of these PROs, and more and more are being developed.

Patients can also play a very important role in the creation of PROs, since they provide relevant information on the impact, on the patient's life, of the treatment that is being evaluated. Researchers can also utilize patients to identify or emphasize any relevant aspect that should be included in the questionnaire. A 2017 study on the level of patient participation in the design of the PROs, found that in most of the studies there has been some participation, but only in a few cases, the patients, have been involved in the complete process.

For diseases, such as cancer , where some treatments are palliative in nature, the quality of life must be considered to be just as important as the improvement in life expectancy of the treatment.

Are PROs used in clinical research?

The short answer is yes, but in many cases, not adequately. Despite the fact that PROs are increasingly integrated into clinical research, and also into regular clinical practice, there are many occasions when they are not used correctly. There is no official body that regulates the design, implementation and interpretation or publication of the results of the PROs.

In order to use a PRO in a clinical trial, you must first know what you want to measure. For some treatments (especially in the case of chronic ones) quality of life will be important, but for others, the reduction of a specific side effect may be more important.

Once the objective has been selected, the PRO must be designed, including both the questionnaire and the instructions for interpretation. Luckily, there are a large number of PROs already developed for very different situations. One of the great advantages of using a PRO that has already been developed is that it is validated, meaning it measures correctly, precisely, reproducibly and easily interpretable.

Just as in the protocol there is all the necessary information to carry out the trial, it should also be integrated, for example, the justification for the use of a specific PRO, what objective is sought when using PROs in the trial, how they are going to be measure and collect data. All this information, unfortunately, is not collected in many trials, which reduces the quality or reliability of the patient surveys.

To understand it better, let's look at an example:

In an oncology trial whose treatment was based on chemotherapy, a PRO was established to assess quality of life after drug administration.

The PRO had to be completed exactly every 21 days, coinciding with the most acute effect of drug administration. But, several patients for various reasons had to delay the administration of chemotherapy for a few days. Since the trial protocol did not specify that the PRO could be completed every 21 days with a window of 2 or 3 days, patients did not complete it when they should be in the acute phase of symptoms, thus rendering the PRO invalid for that period.

In a recent study, a review was carried out on the duration of PROs in different types of cancer, and more specifically those related to quality of life (QoL).It was found that most assessments were at the time the patient took the drug or within the trial but very few looked at QoL after treatment or completion of the trial. Few reached the progression of the disease and almost none reached death. Of the few studies that continued evaluation until the patient's death, only 20% reported improvements in QoL. The study concludes by cautioning that the typical duration of these questionnaires may be inadequate to fully capture the full outcome of treatment on the patient's quality of life.

In addition to better PROs, there are still remains some problems related to the statistical analysis of the results, the publication of results, the lack (although increasingly) participation of patients in the designs, etc... And, even though a notable improvement is being seen in recent years, there is still work to be done.

The importance of using patient questionnaires

Patients are demanding more and more involvement in the execution of clinical research, which will lead to the benefit of having new treatments that can give equal importance to both the efficacy of the treatment and the effects that it can cause on a day-to-day life.

Doctors and researchers have also started to change of treating patients and have started to move towards precision medicine approaches which take into account each individual patient. Some doctors say that years ago the way to help a patient was to run tests and compare the results with other patients, but rarely asked how they felt. With the use of PROs, more accurate and structured data can be obtained directly from the patient and personal information can be collected that would not otherwise be possible.

This development is also important for the pharmaceutical industry since, until recently, the entire flow of information was unidirectional, that is, it went from the patient upwards. But, through the use of new communication technologies and patient empowerment, that is changing. Now patients can research their treatment options and compare the advantages and disadvantages of each one. Due to this and other changes, the industry is placing more importance on the opinions and experiences of patients, while also focusing on seeking clinical benefit.

PROs represent one of the best tools that patients have to be part of clinical research, helping to improve future treatments based on their personal experiences told first-hand. However, there is still a long way to go. We have seen that to this day there is no clear regulation. Without such regulations, different failures that can occur in the process can lead to the PRO being invalid or conclusions unable to be drawn. Another issue is that we are still having researchers write the questions without taking into account the opinion of the patients about what would be important for them to answer.

Fortunately, we are in a process of continuous improvement, and hopefully little by little the necessary changes will be produced to solve all the current problems.


Badia X, Carné X. The evaluation of the quality of life in the context of the clinical trial. Med Clin. 1998 Jun; 110(14): p. 550-556.



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