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Introduction to clinical trials

Two great web-sites to get you started.

One is the National Cancer Institute, which carefully explains the differences between clinical trials, and clinical trial phases, and walks patients through options for enrolling in clinical trials themselves.

The other website is the main website for the United States, http://www.clinicaltrials.gov, which is supposed to list all clinical trials that will results in a drug approved (or not) by the US Food and Drug Administration.

Clinical study reports are written to compile data from clinical trials. The FDA needs to know about every patient who took any amount of drug, every patient who enrolled in the trial. The ICH E3 was compiled by a committee as a guideline of how to prepare a clinical study report. It was published in 1996 and is still the reference guideline. Some drug companies use this guideline as a template.

The essay by Dr Stephen de Looze was written after he served on the ICH3 committee. He is a very senior medical writing director at Sanofi-Aventis in Germany. He is British, went to Germany to do a PhD in insect biology. He lives in Frankfurt with his family.

Clinical Study Report Shells

A document shell is a template plus everything else except the results. A clinical study report template has details from the clinical trial protocol and the statistical analysis plan.

CSR shells are generally written while the medical writer is waiting for clinical data lock. Certainly written before the medical writer is given any data.

Clinical trial data comes in 3 sections: demographics, efficacy data and safety data.

Clinical Study Reports

Narratives

Adverse events result from life happening when the trial participant is taking a does or 2 of a drug a day, and is either spending the day going about normal business, or is in hospital (usually only cancer therapies).

The drug company consults with the FDA to decide when narratives need to be written. A general rule is if a trial participant is hospitalized or the event is considered serious, and the adverse event is known as a serious adverse event, or an SAE. The FDA wants to know if a serious adverse event occurs during a clinical trial, and the study co-ordinator is required to fax in or email notification.

You can see where this is submitted on the FDA website. This document is taken with the final data outputs from the case report forms and a narrative is compiled by the medical writer. These compiled narratives are included in the appendix of the clinical study report.

Every drug company has its own style of writing narratives. Here are 2 styles.

No matter what the style from individual sponsors, what the FDA wants to see are drugs given by their generic name (ibuprofen, acetaminophen) not by the brand names. The brand names can be different all over the world.

Investigator Brochures

An investigator brochure, or IB, can be a massive document by the time a drug is submitted for marketing approval. Everything is in the IB: all preclinical, nonclinical data, as well as clinical data. It is an evolving document, it must be updated even after approval, certainly if post-marketing trials are done.

Clinical Trial Design

Clinical Study Trial Processes