PPI Treatment Studies. The truth about how they are done and why it may not be as scary to use them as you think.
There are typically news headlines about certain drugs being associated with assorted adverse effects. This is also true for PPI drugs. Since PPIs are amoung the most commonly used medicines in the world it's natural that the media will latch on to a medical report when it comes out. After all that is how they make headlines.
The key is to not freaking out (for lack of a better term) when you read a headline that you or a family member or child may be taking is to understand a few words and concepts used in these common reports. There is a lot of fear mongering going on out there concerning PPI use warnings in the treatment of baby reflux.
This article is going to address those studies and shed some light on how they were done so you can draw your own conclusions and how they really apply to the treatment of baby reflux diseases. Because as we've stated time and time again, "Medications such as H2 blockers and proton pump inhibitors should only be considered when the reflux symptoms become a disease. Also, remember that untreated (or poorly treated) GERD has risks as well. The cost benefit of using any medications must be weighed out and a decision must by made using science, the input of your medical care team and family if necessary. But you are the one caring for your infant and making medical desicions for your child.
This page is a great resource for the medical definition of GERD for both adults and infants.
In a 2018 abstract: Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit. Reference
In a March 2019 study: Proton pump inhibitors (PPIs) are used worldwide for the treatment of gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD). Although considered to be widely safe, PPIs have been associated with the potential risk of adverse effects such as infections including pneumonia and Clostridium difficile, malabsorption of vitamins and minerals, dementia and more recently with chronic kidney disease (CKD). Evidence including large cohort studies suggests that there is a greater risk of developing CKD in chronic users of PPIs. However, the association of CKD with PPI use reported in these studies is weak and does not establish a clear causality. This review aims to further investigate the association of CKD with PPI use by including studies with various study designs.
A literature search of published articles with no start date restrictions was undertaken in May 2018 in three electronic databases (PubMed, ScienceDirect, Google Scholar). Search terms included ‘Proton Pump Inhibitors’, ‘chronic kidney disease’, and ‘association’. Both observational and randomized controlled trials (RCTs) investigating the association of CKD with PPI use were eligible for inclusion.
Ten observational studies with 1,005,899 patients contributed to the review. No experimental study was available for inclusion in the review. Of the included studies, six used a retrospective study design, while the rest were prospective (two) or a case-controlled studies (two). A large prospective cohort study with 144,032 patients conducted in the USA reported that PPI use compared to no PPI use was associated with an increased risk of CKD Hazard ratio [HR] 1.28; 95% Confidence Interval [CI] 1.22–1.34. However, the observational study design of this study together with other studies included in the review suggests that the strength of evidence associating PPI use with CKD is weak and does not establish true causality.
The current evidence related to the potential association of CKD with PPI use remains inconclusive in establishing true causality. Further prospective studies including randomized controlled trials and cohort studies would be required to confirm the findings reported in this review and to draw any conclusions.
The list can go on but I think it’s important to understand why these studies don’t validate any dangers associated with long term PPI use. That comes with understanding the difference between prospective and retrospective studies.
What is a Prospective?
A prospective study (sometimes called a prospective cohort study) is a type of cohort or group study, where participants are enrolled into the study before they develop the disease or outcome in question.
The opposite is a retrospective study, where researchers enroll people who already have the disease/condition. Prospective studies typically last a few years, with some lasting for decades.
Study participants typically have to meet certain criteria to be involved in the study. For example, they may have to be of a certain age, profession, or race. Once the participants are enrolled, they are followed for a period of time to see who gets the outcome in question (and who doesn’t). Usually, the research is conducted with a goal in mind and participants are periodically checked for progress, using the same ans questions for each person in the study. Follow ups might include:
• Email questionnaires,
• Phone, internet, or in-person interviews,
• Physical exams,
• Imaging or laboratory tests.
Participants are followed for years and data is collected on the factors of interest, which might include:
• When the subject develops the condition,
• When they drop out of the study or become “lost,”
• When their exposure status changes,
• When they die.
Advantages and Disadvantages
1. Disease outcomes and prevalence are east to calculate.
2. Multiple disease and conditions can be studied at the same time.
3. Researchers don’t have to deal with ethical issues like who receives which treatment (or none at all).
1. All cohort studies can be expensive and time consuming.
2. Confounding variables can be a larger problem with this type of study.
3. Sample sizes are typically very large.
4. Selection bias may be an issue.
1. What is a Retrospective Study?
A retrospective study is an observational study that enrolls participants who already have a disease or condition. In other words, all cases have already happened before the study begins. This is how PPI treatment studies were conducted. Researchers then look back in time, using questionnaires, medical records and other methods; Basically, you just dig into the data and see what you find. The goal is to find out what potential risk factors or other associations and relationships the group has in common.
The opposite of a
retrospective study is a prospective study where participants are
enrolled before any of them have the disease or outcome being
investigated. When both retrospective and prospective methods are used
at the same time, the study is said to be ambi-directional.
Unlike most other studies, a retrospective study collects data that have been previously collected for some other reason than research (Hess, 2004).
2. Terminology Note
In epidemiology (i.e. in clinical studies), “case-control” and “retrospective study” are used synonymously. That’s mostly because when dealing with diseases and conditions, you always want to have a control. A historical epidemiological study without a control would be unthinkable, and perhaps even useless. Therefore, if you look at clinical studies, medical sites, or anything to do with medicine, you’ll find the two terms are interchangeable.
However, in other areas (e.g. education, the social sciences), there are different types of possibility for studies such as a retrospective case series, which do not use controls at all.
3. Advantages and Disadvantages
• Useful for rare diseases or unusual exposures.
• Smaller sample sizes.
• Studies take less time, because the data is readily available (it just has to be collected and analyzed).
• Costs are generally lower.
• Missing data: Exposure status may not be clear, because important data may not have been collected in the first place. For example, if the study is investigating occupational lung cancer rates, information about worker’s smoking habits may not be available.
• Recall bias: Participants may not be able to remember if they were exposed or not.
• Confounding variables are difficult or impossible to measure.
• Retrospective studies are considered to be inferior to prospective studies, so prospective studies should always be used if there is a choice.
• As this is a relatively weak type of study, you cannot make causal statements, although correlations are okay (see: causation vs. correlation). Therefore, getting the study read and/or published may be difficult.
We want to support you in any choice you make when caring for your baby. But it’s important to know all the information prior to making those choices. Yes there is always a cost/benefit to using medications at any age. But over all PPIs are very, very safe for the time frame you would use them to treat your child’s acid reflux.
We hope this information has helped you.