Trial and Error

Clinical trials are an essential part of modern medicine. Trials like the ones run by Clinical Ink are how our medical professionals find out what works, why it works, what doesn’t work, and where they can improve. Without clinical trials, we would not have access to most of the medication and treatments that we take for granted today. Without doctors and researchers taking the time to properly conduct trials, taking note of any adverse effects, positive effects and after effects, medicine simply would not be what it is. 

Before we go into detail about the different phases of clinical trials, let’s take a look at some information about what clinical trials are from a medical point of view.

What Are Clinical Trials?

Clinical trials are a way for medical professionals to test new medications, new methods of diagnosing illnesses, and ways of slowing or preventing illnesses. The goal of any clinical trial is to determine whether these methods of treating or diagnosing medical conditions are safe and effective enough to offer to the general public. During the course of any clinical trial, many things are evaluated:

• Different combinations of medications
• One medication alone
• Medical devices
• New ways of using medications previously used for something else.

Intensive research is done before the trial can even begin, often using human cells or animals. Thankfully animal testing is becoming less prevalent. Funding may be secured for a full clinical trial if the initial results are promising. There are many phases within a clinical trial, each one building on the previous one. Let’s take a look at those phases now.

Phase O

This is the first and most minor phase of the trial, usually including no more than fifteen subjects. Medications or devices are tested in very low quantities or for very short periods. If there are no adverse effects for humans and the results are more or less what the researchers expected, the trial will scale up in the next phase.

Phase 1

During this phase, researchers take whatever time they need or are allotted to scale up their human trials. Now the testing to see how much of the medication or device a human being can handle, without adverse side effects, begins. At this stage, around twenty to eighty people are usually brought in as test subjects. Test subjects are monitored closely for reactions because the human body is unpredictable. In addition to the safety and side effects, researchers also test and take note of the safest and most effective ways to use devices or administer treatments. About 70% of trials make it past this phase.

Phase 2

The trial scales up again in this phase to as many as several hundred subjects. These subjects are people living with the disease that the client aims to help ease or cure, and they are usually given the same safe amount of the medication as the participants in the previous phase. This phase may last for months or even years as researchers monitor their subjects to see how long-term exposure to treatment will affect them. While this clinical trial phase is the largest yet, it is still not large enough to provide sufficient information about the treatment in question. The data collected in phase 2 assists researchers in phase 3. About 33% of trials make it to the next phase.

Phase 3

Once again, the trial will scale up. In Phase 3, trials usually use about 3,000 test subjects in varying stages of the condition in question. This stage of trials can go on for several years. The purpose of such a lengthy phase is to establish how the new medication or device performs compared to existing medications or devices used to treat the illness or condition. For the trial to move forward, there needs to be clear evidence that the new treatment is at least as safe as, but hopefully in some way superior to, existing ones. In this phase, the trial moves into something called “randomization.” Participants are either given the new medication or an existing one to test them against each other; this is usually done in a double-blind format, meaning that neither the researchers nor the participants are aware of who is getting which drug. This method eliminates any bias when interpreting the results. Phase 3 is usually the minimum trial phase for a medication to reach before the FDA will begin their approval process as it is the phase in which most long-term side effects will make themselves known. Between 25 and 30% of trials make it to the next phase.

Phase 4

Phase 4 of any trial only happens after FDA approval. Long-term effects and side effects are monitored as well as any other unexpected benefits. This phase also involves thousands of participants and can go on for many years.

Wrap Up

The numerous phases of clinical trials are all essential, and if any of them are skipped or undertaken without enough care, the results could be disastrous. If you’re applying to be part of a clinical trial, be sure to have all the facts about each phase before you sign up.

Since babies with low birth weight often have poor health outcomes, there is considerable interest in identifying the factors that affect birth weight.  Air pollution has been identified as one possible factor, however several studies have produced conflicting results and there is scarce data from the Middle East region.

A recent study, initiated by Professor Hagai Levine of the Hebrew University showed unequivocally that air pollution is associated with low-birth-weight babies. Using personal, anonymized data and detailed high-resolution pollutant data enabled the Hebrew U. team to produce more accurate statistical analyses. Indeed, Levine maintains, “it is now clear that governments need to set up the infrastructure to integrate environmental and health data at the personal level.”  

This study, led by Wiessam Abu Ahmad, a doctoral student of Levine and Prof. Ronit Nirel at HU’s Department of Statistics and Data Science, looked at the link between an air pollutant known as PM_2.5 and the birth weight of 380,000 singleton babies born to mothers all over in Israel during the years 2004-2015. Their findings were published this week in the prestigious journal Environmental Research.  

Israel, a country with the highest fertility rate among OECD countries and high levels of the air pollutant PM_2.5, made it an ideal location to look for an association between low birth weight and poor air quality. Abu Ahmad explained that as the model included siblings, it enabled the estimation of the variance in low birth weight to be accounted for by variances between different mothers, leading to more accurate estimates. The data used by the research team included: personal anonymized data on the mothers, including the area where they lived and the weight of their babies at birth (provided by Maccabi Health Services); and daily air pollutant concentration over each square kilometer of Israel, derived from satellite data (provided by Ben Gurion University).   

The study clearly showed the association between the level of the air pollutant PM_2.5 and low birth weight.  It also revealed that mothers who were underweight and those of lower socioeconomic status were more vulnerable to exposure to air pollution.  Further, the study found that the association with air pollution was stronger among female babies and first births – a fact that is thought to be due to a biological mechanism that has yet to be identified.     

The association of air pollutants with low birth weight raises the question of whether the Israeli government should take the impact on the developing baby into account and increase its efforts to reduce pollution.  That said, much of the pollution in Israel is carried in by the wind from other countries.    

The findings are, however, an important contribution in identifying a contributory cause to low birth weight. Most importantly, this study breaks new ground in establishing the value of collecting personal detail relating to individuals rather than taking averages over aggregated data.