Q&A: Precision for Medicine VP on the present & future of personalized medicine

© Andrew Brookes / Getty Images
© Andrew Brookes / Getty Images

Related tags Precision medicine Oncology Clinical trial Rare disease

Outsourcing-Pharma caught up with Esther Mahillo, VP of Operational Strategy and Feasibility, Precision for Medicine to talk about advancements in patient enrollment in oncology and rare disease clinical trials.

Outsourcing-Pharma (OSP): Could you please talk about the importance of centering cancer research on the needs of patients?

Esther Mahillo (EM): The low percentage of patients who participate in oncology clinical trials, reported as ranging between 3-8% (1,2), has been identified as a key factor hindering the clinical development of new therapies. This fact has many direct and non-direct consequences, such as that approximately 95% of all the oncology patients are missing the opportunity to access to new therapies through clinical trial offering and participation.

Additionally, this also affects the cost of new drugs (lower patient recruitment rates= longer timelines) and also prevents a broader population to access these new drugs at an earlier stage. There have been ongoing and multiple efforts, among all stakeholders affected by this situation, including Industry, investigators and Patients to analyze the main reasons behind these figures.

The competent authorities in US and European Union, among others, have diligently worked on finding solutions to promote clinical research among patients and enhance participation in clinical trials. As an example, FDA has released several guidance for industry on considerations to facilitate the participation in clinical trials (3), and the European Union has recently released the “Principles of Successful Patient Involvement in Cancer Research” (4) which next step is the broad implementation by National and European stakeholders. 

All parties have come to the conclusion that the next step is to focus on the patients´ needs, involve them on the clinical trial development, and listen to their feedback on barriers and solutions to facilitate their participation in the studies.

OSP: How do needs of patients in clinical studies change when the cancer in question is a rare cancer?

Esther Mahillo headshot
Esther Mahillo, VP of Operational Strategy and Feasibility, Precision for Medicine

EM: Patients with rare indications, including oncology ones, usually face multiple challenges, including late or misdiagnosis (which usually impacts on life expectancy), wrong treatments, and logistical and practical difficulties to access to the appropriate therapies.

Some of these rare pathologies, like those affecting the central nervous system, may require specific technology or specialized personnel, which may be only available at a limited number of institutions per country. This implies the need for the patients (and their families) to travel to these locations and potentially stay there for extended periods of time.

When the performance status of the patients gets deteriorated, as a consequence of the pathology, travelling can become an issue. Therefore, identification of patient-centric solutions are paradigm to balance the therapeutical needs with the quality of life.

OSP: Could you please share some of the challenges the trial teams themselves face when their study centers around a rare cancer?

EM: We can establish 3 different categories of challenges that trial teams may face when running clinical trials in rare disease indications:

-        Study design: Sponsors and Regulators have established guidance and rules around designing clinical protocols for the research of rare indications, that may clash with the reality of the patients´ lives. We recommend to involve the patients or their representatives during the protocol development, through some of the professional organizations which can conduct feasibility pools to check the viability of study processes and visits schedules. Any design which translates into extra burden, or excessive hospital visits, or both, should consider the offering of adequate mitigation measures, such as home nursing, telemedicine, conduct of certain study visits at centers located near patients ‘homes, etc. Feasibility of certain tests should also be assessed before the protocol finalization, especially for pediatric or vulnerable populations.

-        Bridging therapeutical options: Sponsors and Regulators should consider in advance of the clinical trial how its results will influence the patients´ lives once their participation has been completed. Expanded access studies is one option to allow for continuation of study therapies, but it is equally relevant to accelerate the access of the broader population to new effective therapies

-        Patients´ beliefs and prejudices: the journey of patients with rare diseases (and their families) is generally arduous and difficult. Patients may be reluctant to participate in clinical trials with innovative drugs, like gene therapies, which imply a high level of uncertainty and long safety oversight. Additionally, taking part in studies with drugs never tested before in human beings, or with a placebo control arm, may contribute to grow this resistance, unless the rationale, risks and potential benefits are carefully explained in a language accessible to plain people. The extra burden (visits, tests, travel, etc.) related to participation in clinical trials, may influence the patient´s decisions, unless they are offered a solid mitigation plan, as discussed before. Even so, we need to consider that 1 out of every 3 potential patients may decline participating in clinical trials.

OSP: Specifically, what are some of the challenges they face identifying and enrolling patients?

EM: There are usually well-established networks of investigators specialized on certain rare indications. Therefore, identification of investigators who will take part in a rare-disease study should be feasible. The main challenges are related to the identification of potential patients to participate in the clinical trial.

The investigators usually hold an internal database with the patients diagnosed, treated and/or followed at their respective institutions. However, the pool of patients gets restricted when checked for protocol eligibility criteria. Normally, the trial team will need to implement additional measures to enrich the potential patient’s population, such as:

  • Study advertising and promotion through social media
  • Interaction with advocacy groups
  • Network of referral sites- which implies also implementation of DCT measures to facilitate the patient’s participation (for example, concierge services to coordinate travel and stay for patient and/or family; investigational drug delivery at patient´s home; telemedicine for selected study visits; etc.)
  • Some clinical trials in rare or ultra-rare disease indications may need a high number of extra activities in order to secure a timely enrolment of patients.

OSP: You mention that new biological targets often have a low level of prevalence—how does that require study personnel to get creative and smarter in their approaches?

EM: The so-called “patients funnel” may require the pre-screening of hundreds, even thousands of potential patients, to finally enroll several dozens in the clinical trial. Access and engagement of these potential patients is the main challenge in the context of rare disease clinical trials. Apart from the activities mentioned above, the conduct of these studies may require the implementation of a screening study to be run separately from the clinical trial itself.

The screening study is intended to triage eligible patients based on one specific biomarker, for example, a certain HLA allotype required to elicit a drug-mediated immune response. As of September 2022, the search in clinicaltrials.gov of screening trials renders 160 results, of which, 60 correspond to active screening studies.

Other creative solutions include partnering with internal stakeholders, like Precision Biospecimen group, which can leverage their biobank information to identify potential patients based on a biomarker-specific search or can create and manage a biospecimen collection for the pre-screening or screening in a specific context.

OSP: Please talk about the increasing complexity in biomarker-driven studies and how that specifically makes a trial team’s job harder.

Some biomarker-driven therapies were developed decades ago, like those prescribed for some hormone-related tumor types, like anti-estrogen or anti-progesterone treatments in breast cancer, or anti-androgen therapies in prostate cancer. However, with the rapid advances in the understanding of the role of genes and gene modulation in the oncogenesis, as well as the accelerated technical developments in gene sequencing and analysis, have driven the identification of many biomarkers which, although low prevalent, may present a high carcinogenesis impact, and a high biological complexity (for example, families of biomarkers with different prevalence and impact, depending of the tumor type).

To give an example of the level of complexity of biomarker-driven studies, the fibroblast growth receptor (FGFR) family spans 4 different receptor types: FGFR1, FGFR2, FGFR3 and FGFR4. FGFRs play an important role in cell proliferation, survival, and migration, as well as angiogenesis, and can be involved in development of several oncology diseases.

The 4 members of the FGFR family can be involved in oncogenesis processes, through multiple somatic aberrations, such as chromosomal amplification of FGFR1; mutations and multiple dysregulations of FGFR2; and mutations, translocations, and significant amplifications of FGFR3 and FGFR4 (5). To contribute to the level of complexity, these FGFR alterations may occur at the same time, and their frequency varies depending of the tumor type, as summarized in the picture below (6).

Cancer types for Precision for Medicine article


Drug development plans for targeted therapies need to consider both the frequency of expression of the specific biomarker in a patient population, and introduce upfront the concept of patients ‘identification in advance of site selection, and not the other way round. And once again, the study plan should consider all and any possible activities aimed to facilitate the enrolment and retention of the patients in the clinical trial, especially those falling under the umbrella of the so-called decentralized clinical trials management.

OSP: Could you please talk about the recent advancements in personalized medicine—in general, and with rare cancers specifically?

EM: Personalized medicine consists of the timely​ administration of a medical treatment tailored to the individual characteristics​ of each patient.

Probably, the paradigm of personalized medicine is the autologous cell therapy, which manipulates the individual patient´s cells to transform them in drugs. The FDA has approved 5 different autologous cell therapies in the last 5 years, for the treatment of 11 different hematology malignancies. These cell therapies have addressed unmet medical needs for rare oncology indications with poor prognosis, which previously had none or scarce therapeutical options. The table below summarizes the key information related to these cell therapies (7):

CAR-T Product





3L+ Large B cell lymphoma


Locke et al, The Lancet Oncology, 2019


3L+ Indolent (FL, MZL)


Jacobson et al, The Lancet, 2021


2L Large B cell lymphoma


 Locke et al, NEJM, 2022


2L Large B cell lymphoma


Kamdar et al, The Lancet, 2020


3L+ Large B cell lymphoma


Abramson et al, The Lancet, 2020


R/R Mantle cell lymphoma


Wang et al, NEJM, 2020




Shah et al, The Lancet


3L+ Large B cell lymphoma


 Schuster et al NEJM, 2019


3L+ Follicular lymphoma


 Fowler et al. Nat Med, 2022


4L+ Multiple myeloma


Munshi et al, NEJM, 2021


4L+ Multiple myeloma


Berdeja et al, NEJM 2021


All these 6 drugs are autologous cell therapies, based on the genetic manipulation of T-cells obtained from each individual patient, usually through a viral vector. The process to develop each treatment is lengthy and complex. Patients are first treated to enrich their T-cell population, then subject to apheresis to harvest these cells, which need to be sent to a central manufacturing location qualified for the genetic manipulation and growth of selected T-cell clones. Hospital needs a special qualification and premises to conduct cell therapy studies, same as their staff. The complexity of conducting these clinical trials is usually compensated by their positive results and accelerated approval of these new therapies for patient populations in dire need of them.

Autologous cell therapies are under development also in other therapeutic areas, such as cardiovascular disease, peripheral arterial disease, liver disease, diabetes, neurodegenerative disorders, bone repair, and spinal cord injuries, with more than 1,000 active studies found in clinicaltrials.gov by September 2022.

OSP:In your recent presentation, you talk about your organization’s ‘paradigm’ and how it: 1. Fosters a study-individualized approach, 2. Encompasses fit-to-study strategies, 3. Is based on fluid interaction with partners. Could you please elaborate?

EM: As previously discussed, conducting clinical trials with personalized medicine encompasses multiple layers of complexity, including the difficulty to identify, enroll and retain patients in these studies; the limited number of investigational sites qualified for the conduct of these trials; and the recommendations from the Regulators, which often require long, and complex safety follow up periods. All these factors contribute to a significant cost increase in drug development, which ultimately translates into high prices, often unaffordable for patients and health systems.

Precision for Medicine is shifting the paradigm of clinical research in the context of personalized medicine, and specially for rare indications, and/or low frequently expressed biomarker targets.

The first step in our process is to identify where the eligible patients are, to later define the best option to enroll and treat them, in the context of a fluid environment where the study gets adapted to each patient´s needs. There is not one simple or unique solution. Just the opposite. Precision´s teams work on the principle that many different approaches, either facilitated by us, or by our partners, will be needed to succeed. Some of these options are listed below:

  • Precision´s Biospecimen Solutions team can scan their biobank to identify potential patients, or can set up a pre-screening study to triage those patients who qualify for participation, therefore narrowing the patient´s funnel
  • Precision´s HeOR can facilitate the technology to support sites with HER data mining, in order to accelerate the identification of study patients
  • One partner company can leverage this same approach, data mining, through their site network, to identify and refer potential patients for participation in the clinical trial
  • Precision can conduct expedite feasibility among the Precision Site Network (PSN) sites, to identify trends, risks and potential solutions to the challenges posed by personalized therapies under development
  • Several partner companies can provide blinded data on next-generation sequencing (NGS) requested or conducted for a certain biomarker, with a level of granularity allowing to know which are the hospitals involved in these requests and therefore, where the potential patients are located.

These are some of the strategies that can be utilized for the identification of the study patient population, which will determine the best option for site selection (one central institution (hub) with multiple referral (spoke) sites just-in-time activation of sites located close-by the patients, Etc.

Lastly, Precision´s teams work in parallel on implementation of strategies aimed to facilitate the participation and retention of the patients in the clinical trial, which is also critical for the analysis of results. These strategies, like concierge services, telemedicine, home nursing, home IP release, supporting technology, etc. can be provided by Precision for Medicine, and/or our partner.

OSP: Do you have anything to add?

EM: To conclude, personalized medicine is our present and future way to advance in the development of new therapies in many therapeutic areas, but prominently in oncology and rare disease indications. Industry and CROs have got quickly adapted to this new environment, where collaboration among institutions but also between different companies is a key to success, but there is a lot to do to get patients aligned to this new way in drug development process.

We need to better convey the message for our patients, that their biological sample analysis may be key for present and future access to new personalized treatments. Finally, we need to work together with patients’ associations to overcome cultural and ethical concerns that interfere with access to novel advanced therapies in clinical trials.


1.- “Trial-In-A-Box” to help more practices take part in clinical trials.
Tanya Albert Henry​.  MAY 27, 2021. AMA digital publication. https://www.ama-assn.org/practice-management/digital/trial-box-help-more-practices-take-part-clinical-trials

2.- Joseph M Unger, Riha Vaidya, Dawn L Hershman, Lori M Minasian, Mark E Fleury, Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation, JNCI: Journal of the National Cancer Institute​, Volume 111, Issue 3, March 2019, Pages 245–255, https://doi.org/10.1093/jnci/djy221

3.- https://www.fda.gov/news-events/fda-brief/fda-brief-fda-takes-new-steps-broaden-patient-participation-cancer-clinical-trials-advancing

4.- https://www.gesundheitsforschung-bmbf.de/files/2021_06_01_Principles_Paper_bf.pdf

5.- Ardizzone A, Scuderi SA, Giuffrida D, Colarossi C, Puglisi C, Campolo M, Cuzzocrea S, Esposito E, Paterniti I. Role of Fibroblast Growth Factors Receptors (FGFRs) in Brain Tumors, Focus on Astrocytoma and Glioblastoma. Cancers (Basel). 2020 Dec 18;12(12):3825. doi: 10.3390/cancers12123825. PMID: 33352931; PMCID: PMC7766440.

6.- Helsten T. et al. The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing. Clin Cancer Res 2015;; 22(1); 259–267.

7.- REFCAR (quarto.pub)



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