March 2018

The Pulse

A Successful Clinical Trial Begins with the Study Start-Up Phase

March 12, 2018

The study start-up phase sets the tone for a clinical research trial and is crucial to the overall success of a program. The critical nature of this phase places significant pressure on all stakeholders. The strength of the relationship between the site and CRO during study start-up is an important factor in creating a successful study outcome. Rather than a customer and vendor relationship, sites and CROs should strive to develop strategic alliances, partnering seamlessly through an entire clinical study and beyond. The study start-up stage offers ample opportunities for sites and CROs to establish the foundation of a trust-based relationship.


Tufts CSDD: Clinical Trial Startup Process Takes Longer Than 10 Years Ago

March 12, 2018

The process of selecting clinical trial sites and launching studies, beginning with site identification and ending with study start-up completion, takes an average of 31.4 weeks for Phase II and III studies — a full month longer than the average seen 10 years ago, according to a survey conducted by the Tufts Center for the Study of Drug Development.

Between 30 and 40 percent of 590 sponsors and CROs said they were somewhat or completely unsatisfied with their processes for site initiation, according to the study. Respondents reported that 61 percent of total cycle time was associated with study start-up activities such as contract and budget negotiations.

Tufts researchers found the widest variations among respondents in site identification cycle times, indicating “highly inconsistent practices,” the report said. Nearly three in 10 sites were new, with no prior history of working with a sponsor or CRO.

Tufts CSDD senior research fellow Mary Jo Lamberti, who led the analysis, said drugmakers are trying to improve the timeliness of the site initiation process.

Sponsors are investing in technology and working to make contracting and budgeting negotiations — which can be a significant drag on the process — more efficient, Lamberti told CWWeekly.

“It’s happening, but it’s just not happening fast enough,” she said.

Another potential solution, Lamberti said, is pooling data from clinical sites to counter the siloing of data common among drug manufacturers. Sharing information with sites early on to assess study feasibility could enhance the site selection process, according to the Tufts report.

Tufts researchers found that CROs are more efficient than drug sponsors, completing initiation an average of 5.6 weeks faster for repeat sites and 11 weeks faster for first-time sites. This was “very telling because there isn’t a lot of research out there comparing cycle times between sponsors and CROs,” Lamberti said.

CROs make more use of advanced technology solutions for the study initiation process than drug sponsors, according to Tufts researchers, with 47 percent of CROs saying they used clinical trial management systems compared to only 28 percent of sponsors. More than half of sponsors still rely on spreadsheets, compared to just under one-third of CROs.

In addition, 10.9 percent of initiated sites are never activated — a constant figure over the past 20 years, according to Tufts — with sites being managed by CROs being activated more often.

More information can be found at

By Zack Budryk


CTTI Investigates Barriers to Conducting Pediatric Antibacterial Clinical Trials

March 12, 2018

Pediatric antibacterial drug trials currently account for less than one percent of all interventional and observational pediatric studies registered on between October 2007 and September 2015, or only 82 out of 12,703.

According to a series of surveys conducted by the Clinical Trials Transformation Initiative, three of the four major barriers identified by respondents were related to parental involvement and consent.

They included obtaining consent when there is evident disagreement between two parents, parental concerns about the number of blood draws and invasive procedures required by the study protocol. Many parents are reluctant to give consent when they see no direct benefit for their child in a clinical trial and are happy with current care, one respondent said.

Interviews with parents found that each aspect of a study, from initial explanations to reporting the final result, can affect willingness to provide consent. Establishing trust and empathy, as well as providing clear transparency on any risks and benefits, were key decisionmaking factors, CTTI said, describing how parents’ priorities must be incorporated early into trial design for accrual to be successful.

All survey participants strongly preferred to hear about a clinical trial opportunity first from their child’s own pediatrician or from a doctor caring for them in the hospital — rather than being cold-called by a researcher or a stranger. In addition, being approached too soon or too often can be a detriment, such as during the first few days after birth, in the case of premature newborns in neonatal intensive care.

The remaining barrier related to overly narrow inclusion and exclusion recruitment criteria, including prerequisites disallowing the use of other antibacterial drugs prior to enrollment.

Additionally, finding study coordinators with sufficient experience was a significant challenge, with one respondent recommending long-term staff support to help avoid constantly training new staff for each trial.

CTTI’s study identified several recommendations to help facilitate more studies. For example, pediatric trial networks can facilitate development and eliminate the need for startup with each new trial, as well as help standardize site resources and funding.

Another main factor was the ability to recruit study participants directly from the investigators’ own practice, the surveys found. Having dedicated staff available to enroll patients in inpatient studies with little advance warning, potentially 24 hours a day, was described as a major benefit.

Established referral systems, interdisciplinary collaborations and access to the hospital inpatient database were all listed as crucial for recruitment, and supporting the buy-in of other practitioners for their pediatric patients to enroll.

—by Conor Hale @conorhale


EMA Revises Guidance on Biomarkers for Alzheimer’s Therapies

March 12, 2018

The EMA’s Committee for Medicinal Products for Human Use revised its guideline on the clinical investigation of treatments for Alzheimer’s disease, focusing on the design and analysis of safety studies and the potential use of biomarkers in various stages of development. The revision, which takes effect on September 1, separates biomarkers according to their potential use: diagnostic, enrichment, prognostic, predictive and pharmacodynamic. The guideline notes that while most biomarkers still require validation for these purposes, cerebrospinal fluid markers, as well as MRI and PET imaging markers, “are qualified for the enrichment of study populations,” even though the biomarkers have not been qualified for use in preclinical Alzheimer’s disease. Identified adverse events should be categorized in relation to the treatment duration, applied dosage, recovery time, different age groups and other variables, the guideline said, and all adverse events occurring during clinical trials should be fully documented with a separate analysis of adverse drug events that lead to drop-outs and fatal outcomes. The revised guideline is available here:


Pipeline new from Seattle Genetics, Daiichi Sankyo, Aimmune Therapeutics, Polyganics and more

March 12, 2018

Company Drug/Device Medical Condition Status
Seattle Genetics, Inc. SGN-CD48A Relapsed or refractory multiple myeloma Phase I trial initiated enrolling 75 subjects
Daiichi Sankyo Company, Ltd. DS-8201 HER2-expressing advanced colorectal cancer Phase II trial initiated enrolling 50 subjects in North America, Europe and Japan
GTx, Inc. Enobosarm Stress urinary incontinence (SUI) Phase II trial initiated enrolling 18 female subjects
InflaRx IFX-1 Moderate or severe Hidradenitis Suppertiva (HS) Phase IIb trials initiated enrolling 175 subjects in the U.S., Germany, Greece, Denmark and the Netherlands
Aimmune Therapeutics, Inc. AR101 Peanut allergy Phase III trials initiated enrolling 850 subjects ages 4-49
Vanda Pharmaceuticals, Inc. Hetlioz Jet lag disorder Phase III trials initiated enrolling 318 subjects
Biohaven Pharmaceutical Holding Company Ltd. Zydis ODT formulation of rimegepant Migraine Phase III trials initiated enrolling 850 subjects
Bioverativ, Inc BIVV009 Cold agglutinin disease Phase III trials initiated
MeiraGTx AAOO2 Achromatopsia PRIME designation grated by the EMA
Tocagen Inc. Toca 511 (vocimagene amiretrorepvec) & Toca FC (flucytosine) Glioma Orphan drug designated granted by the EMA
InVivo Therapeutics Holdings Corp. Neuro-Spinal Scaffold Acute spinal cord injury (SCI) FDA approval granted
Polyganics Liver and Pancreas Sealant Patch Fluid leakage after hepato-pancreato-biliary (HPB) procedures FDA breakthrough device designation granted
Trial Results

Bioverativ Announces First Patient Dosed in Study for Treatment of Cold Agglutinin Disease

March 12, 2018

Bioverativ announced that the first patient has been dosed in the Phase III clinical program of its investigational therapy BIVV009 for cold agglutinin disease (CAgD). The Phase III program includes two parallel Phase III trials, Cardinal and Cadenza, which are evaluating the efficacy and safety of BIVV009 in adult patients with primary CAgD, a disease with no approved therapies. The study assessed the long-term efficacy, safety and PK/PD profile of BIVV009 in six severely anemic primary CAgD patients. Primary and secondary outcome measures were achieved in the CAgD patients in the study. Hemoglobin levels increased in all six patients (median >4g/dl) which eliminated the need for transfusions while on treatment. There were no serious AEs assessed as related to BIVV009 by the investigator.

Research Center Profiles

March Top 10 Research Center Profiles

March 12, 2018

Research Center Spotlight is a monthly selection of clinical research centers who have Research Center Profile pages posted on Included in their annual subscriptions, company profiles are randomly selected to appear in this section, providing added exposure for their expertise and services in conducting and managing clinical studies. To learn more about becoming an Research Center Profile page subscriber, contact Sales at (617) 948-5100.

The Pulse

Evaluate New Investigative Sites Holistically

March 5, 2018

Investigational sites must be evaluated based on each element of contribution to form a fully dimensional picture for study consideration. Some sites excel at recruitment, but lack therapeutic expertise. Some sites with inexperienced staff have tactical/logistical expertise. Those sites lacking in some areas may tip the scales in their favor with other valuable strengths. We may miss out on good sites if we do not consider the entire picture.