New FDA draft guidance points to problems with multiple endpoints in clinical trials

FDA clinical trials draft guidanceThe US FDA released draft guidance this week on the “problems posed by multiple endpoints in the analysis and interpretation of study results and how these problems can be managed in drug and biologic clinical trials,” Zachary Brennan of RAPS reports. The FDA justifies the guidance due to the greater likelihood of making false conclusions about the effects of a given drug as the number of endpoints in a single clinical trial increases.

The FDA states that the guidance serves to “describe various strategies for grouping and ordering endpoints for analysis and applying some well-organized statistical methods for managing multiplicity within a study in order to control the chance of making erroneous conclusions about a drug’s effects.” (FDA Draft Guidance). Efficacy endpoints measure a drug’s effects. They may include assessments of clinical events (e.g. mortality, pulmonary exacerbation), patient symptoms (e.g. pain, depression), measures of function (e.g. ability to walk or exercise), or surrogates of these events or symptoms. The draft guidance lists the three families for classifying endpoints within a clinical trial: primary, secondary, and exploratory. To demonstrate the study objective of effectiveness, a statistical analysis must be performed to rule out chance as the explanation for a trial’s results. The guidance goes on to discuss the test of hypothesis and several other statistical methods used within clinical research to test against the probability of chance.

The FDA’s explanation of various statistical models and their usage cases dominates the rest of the draft guidance. However, this in-depth analysis drives home the message of this guidance. The FDA states that “the chance of making a false positive conclusion, concluding that a drug has a beneficial effect when it does not, is of primary concern” (FDA Draft Guidance). Our team of experts at Pearl IRB strive to stay up to date with FDA’s guidance to ensure that our clients remain informed about the necessary regulations. This allows clinical trials to run smoothly as our clients march towards product commercialization. If you have a study that needs reviewed or are in the beginning phases of research for a new treatment, please contact us today.

FDA Issues Official Withdrawal of Proposed Rule Concerning Public Disclosure of Unapproved Gene Therapies

Two weeks ago, the US Food and Drug Administration (FDA) announced the withdrawal of a proposed rule from 2001. The rule would have required the public disclosure of summaries of safety and effectiveness data from pre-market clinical trials of gene therapies and transplanted non-human tissues to humans.

In its notice of withdrawal, the FDA announced “[we have] reconsidered our position on the issue and deemed our concerns from 2001 outdated. We will continue to assess whether rulemaking in this area is necessary, and if so, we will proceed with a new proposed rule.”

RAPS explains that “non-proprietary and non-trade secret information and data related to investigational new drug applications (INDs) for xenotransplantation and gene therapies would have been disclosed.” RAPS goes on to detail the categories of information that would have been disclosed under the rule:

  1. product and patient safety data and related information, including results from preclinical and clinical studies and tests that demonstrate the safety and/or feasibility of the proposed procedures
  2. the name and address of the sponsor
  3. the clinical indications to be studied
  4. the protocol for each planned study, including a scientific abstract and a nontechnical abstract, a statement of the objectives, purpose, and rationale of the study, the name and address of each investigator, the name and address of the official contacts of each local review body as appropriate (IRB, IBC) and dated copies of approval by each group, the criteria for patient selection and exclusion, an estimate of the number of patients to be studied, a description of the treatment that will be administered to patients, and the clinical procedures, laboratory tests, or other measures to be taken to monitor the safety and effects of the drug in human subjects and to minimize risk
  5. written informed consent forms
  6. identification of the biological product(s) and a general description of the method of production, including a description of product features that may affect patient safety
  7. IND safety reports
  8. information submitted to FDA in an annual report
  9. the regulatory status of the investigation, the date of such action and the reason for such action
  10. other relevant data and information that the director of the Center for Biologics Evaluation and Research determines as necessary for the appropriate consideration of the public health and scientific issues, including relevant ethical issues

The FDA closed their notice of withdrawal by stating “the withdrawal of these proposals identified in this document does not preclude the Agency from reinstituting rulemaking concerning the issues addressed in the proposals listed in the chard. Should we decide to undertake such rulemakings in the future, we will re-propose the actions and provide new opportunities for comment.” If your company needs help navigating the FDA’s ever-changing rules and the complex regulatory landscape, please contact us.

Obama nominates Robert Califf as FDA commissioner

With the previous resignation of Commissioner Margaret Hamburg, there has been talk that current deputy commissioner for medical products and tobacco, Robert Califf, may soon be the new US FDA commissioner.

Concurrently, the US Senate is working to permanently expedite the process of FDA drug approval through legislation. For Zachary Brennan’s full article, click here. For an additional article on this topic, check out Medscape.

Pearl Employee Publishes Article on

Pearl Pathways is proud of employee Heidi Strunk, as she earned a publication in the RAPS online journal Regulatory Focus.  The article is located on (Login and Password required) and is entitled Types of In Vitro Diagnostics: Clearing Up the Confusion.”

By definition, all in vitro diagnostics (IVDs) for human use are medical devices. This is easily understood – however, with an abundance of acronyms, IVD classification can become complicated. To clear up the confusion, this article considers six types of IVDs:

  • Research Use Only (RUO)
  • Investigational Use Only (IUO)
  • Analyte-Specific Reagents (ASRs)
  • Laboratory-Developed Tests (LDTs)
  • Companion Diagnostic IVDs
  • In Vitro Diagnostic Multivariate Index Assays (IVDMIAs)

There are a number of hurdles to bringing a new medical device to the market, but product classification does not have to be one of them.  This article is a must read for anyone involved in the development of IVDs. Read full article on here.

Join Pearl Pathways at the 5th Annual Clinical Affairs and Regulatory Approvals for Diagnostics Conference

Pearl Pathways is excited to be attending and presenting at the Annual Clinical Affairs & Regulatory Approvals for Diagnostics Conference next week in Alexandria, VA. This conference provides a forum for discussion on the challenges regulators face and strategies used to successfully bring a companion diagnostic to market. This year’s attendees include FDA reviewers, accomplished industry representatives, and numerous regulatory experts.

We encourage you to stop by our booth to meet our talented staff. In addition, we invite you to join us for the Clinical & Regulatory Strategies for Companion Diagnostics Workshop on Wednesday, October 29. Pearl Pathways’ own Gretchen Bowker will be serving as the moderator for the 11:20 discussion on Establishing Realistic Timelines for Companion Diagnostics & Personalized Medicine Development.

Click here to register for the conference. We hope to see you in Alexandria on Monday!

2014 RAPS features Gretchen Bowker as a speaker

Pearl Pathways’ own Gretchen Bowker will be speaking at the 2014 RAPS Preconference Workshop entitled Regulatory Strategy Forum for Biologics. She will be presenting at the 11am session on conducting clinical trials, which will cover the roles and responsibilities of sponsors, investigators, IRBs, and regulatory authorities as they relate to the development of biologic products.


What: Regulatory Strategy Forum for Biologics

When: 9 a.m. to 5 p.m. on Saturday, September 27

Where: 2014 RAPS Preconference Workshops (Meeting Room 16A)

Register here!


We hope to see you soon at 2014 RAPS: The Regulatory Convergence in Austin!

FDA adopt guidelines from ICH

Alexander Gaffney from has just released an article on regulators releasing the latest guideline on electronically transmitting individual case safety reports (ICSR) from the International Conference on Harmonisation’s (ICH). ICH is a pharmaceutical harmonization group that is run by US FDA, European Medicine Agency (EMA), and Japan’s Ministry of Health, Labor and Welfare (MHLW). ICH aims to have regulatory processes better align with different administrations allowing for greater efficiency between industry and regulators. The final guideline, E2B(R3) Electronic Transmission of Individual Case Safety Reports Implementation Guide — Data Elements and Message Specification, provides an outline for the data, terminology, and exchange standards for ICSR submissions to improve the quality of data and improve the analysis of the documents. To read the full article click here.

Setback for EMA’s vision of transparency journalist, Alexander Gaffney reported that an EU court has surprisingly issued an interim order that the European Medicines Agency (EMA) should stop publishing any more information or documents until a final order has been passed regarding public information. This is a setback for the EMA, whose goal is to make public all clinical and non-clinical data.  Proponents of data transparency include the people behind the AllTrials campaign, whom have the same goals as the EMA. Companies such as Abbvie and Intermune, leaders in drug and medicine innovation, have fought the idea of transparency. They have sued the EMA on grounds that the information publicized is “commercially confidential information”, in which the EU court agreed with.  EMA’s head of communication, Mark Harvey, commented on the situation via Twitter saying “disappointing, but not the end”. EMA will appeal the court’s ruling and continue with their battle to make all data and information publicly available. Is this the next step in clinical data? To read the full article click here.

Save the Date: February 25, 2013 RAPS Indiana Chapter networking event

Join Pearl Staff at the ‘Celebration of Life Sciences in Indiana Networking Reception’ hosted by the RAPS Indiana Chapter.  The focus of the event is to promote new connections among local regulatory professionals. A BioCrossroads representative will also provide an update about the life sciences in Indiana.

What: Celebration of Life Sciences in Indiana Networking Reception

When: February 25, 2013

Time: 4:30-6:30pm

Where: Faegre Baker Daniels LLP, 600 E. 96th Street Suite 600, Indianapolis, IN

Directions are available online or by calling +1 317 569 9600

Contact Cindy Killion at to RSVP.

To learn more about RAPS Indiana, click here.

September 11, 2012–RAPS presents “The New FDA Landscape in Medical Device Development”

The RAPS Indiana Chapter presents the expert presentation, “The New FDA Landscape in Medical Device Development.”

Where: MED Institute Inc., West Lafayette, IN

When: September 11, 2012 from 5:15 – 8 p.m.

Cost: $40 for non-members and $25 for members

Stay current on FDA activities that are affecting device development and exchange ideas with other local regulatory professionals.

This interactive discussion will include a meal for all participants, and attendees may claim two RAC recertification points.

To register and learn more about this event, click here.