Canvassing: Recruitment of Patients with Rare Condition in Clinical Trials – Sharing Experience from our Perspective

By Ranita Kirubakaran (Clinical Pharmacist, Hospital Sultan Abdul Halim, Kedah), Vijaya Kumar L. Suppan (Head of Orthopaedic Department & Clinical Research Centre, Hospital Sultan Abdul Halim, Kedah)

 

Acute hematogenous osteomyelitis (AHO) is an inflammatory disorder of the musculoskeletal system and mainly, a disease of growing bones. It is a common invasive infection in paediatric and the incidence is 8 cases per 100,000 children/year [1, 2]. In children, osteomyelitis (OM) arises from bacteremic seeding of the bone metaphysic [3]. Primary bones affected are femur, tibia, humerus and less frequently, pelvis and vertebra [3]. Staphylococcus aureus is the most common pathogen, causing between 25 – 60% of cases with known etiologies [4, 5, 6].   Other causative bacteria include Streptococcus pyogenes (Group A streptococci), Kingella kingae and Haemophilus influenza type b [4, 5]. Children are treated empirically with intravenous (IV) therapy directed against the likely pathogen and then, guided by culture results with continued IV or oral therapy.

Recently, our institution was selected to conduct an orthopaedic based Industry Sponsored Research (ISR). The study is a multicenter, randomized double-blinded comparative study to evaluate the efficacy, safety, and pharmacokinetics of an investigational product versus an active comparator in paediatric subjects with AHO due to gram-positive organisms.  The study   was   approval by  Medical Research and Ethics Committee (MREC) and only four public hospitals in Malaysia were involved in this ISR. The target was to recruit at least 3 patients per centre. As the coordinating principle investigator in Malaysia, our institution aimed to recruit and enroll at least one patient for the study, despite the fact that we were given only 3 months for patient recruitment, bearing in mind that AHO is a rare case with poor patient pool at our institution.  Also, the study protocol was quite challenging. The study required us to recruit children with acute onset of OM, fulfilling 3 clinical symptoms parameters (pain, inflammation and limb function) with radiologic confirmation of AHO. In addition, subject should not have prior exposure to any effective antibiotic therapy for AHO.

Being a novice in ISR, our team brainstormed on ways to recruit such rare subjects for the study. Our institution decided to opt for a special approach, namely canvassing where our team consisting of doctors and pharmacists would canvas the nearby public hospitals and district health clinics during lunch break. We provided a short power point presentation to the doctors on the patient pool that we were looking for and ways for them to refer potential patients to us. Slide presentation handouts were distributed to healthcare professionals together with our team investigators contact numbers to facilitate referral. Refreshments were provided for those who attended the talk thereafter. Sponsor approval and budget allocation were obtained prior to canvassing. We managed to cover 4 district hospitals and 3 district health clinics. Permission was obtained from the hospital directors and family medicine specialists at the district health clinics prior to our visit.

 

Flow chart from canvassing till patient recruitment:

One Medical Officer (MO) was elected as a coordinator at each health setting to facilitate referral and patient recruitment irrespective of time with prior consent from the parents and patient to be transferred to our hospital for further management. We emphasized that their support for the study, in the form of patient referral, would be greatly appreciated as we assured them that the patients will be given high standard of care. Our involvement will be strictly study-related and referral doctor(s) will be notified if patient is enrolled. In addition, we decided to provide referral fees to doctors who referred potential patients to us, if the patient is successfully recruited in the study.

From our approach, we managed to recruit one patient into the study through referral from one of the public hospitals which we covered during canvassing. The 1 year 4 month old child was transported and admitted to the orthopaedic ward in our hospital at 5.00 pm. Patient’s parents were explained regarding the intensive study protocol especially on the frequency of blood taking and were given adequate time to think and read the consent form. Once consented, we conducted steps as per protocol such as blood taking, magnetic resonance imaging (MRI) which was done externally and etc. Once inclusion criteria were fulfilled, randomization was made at 12.00 am. The first dose of drug was given to the patient at 1.00 am.

We were the sole institution in Malaysia which managed to recruit patient for the ISR. Thus, canvassing is a way to go for patient recruitment in rare conditions for any clinical trials.  Our method of recruitment  was audited  by  a Senior  Consultant  from Falcon

Consulting Group, Inc, America and we were awarded with a Good Clinical Practice Services Audit Certificate. Lastly, we would like to take this opportunity to thank all the team members who worked very hard to ensure the study was a successful one.

 

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Acknowledgement to the team members:

  1. Dr. Choo  Chong  Ming,  Head  of Paediatric Department & Infectious Disease Consultant
  2. Dr. Kartina Binti Md Noor, Head of Pathology Department
  3. Dr. Tan Chin Siong, Medical Officer (Orthopaedic)
  4. Dr. Chew Yu Wei, Medical Officer (Orthopaedic)
  5. Dr. Vijay Kumar A/L Nanta Kumar, Medical Officer (Orthopaedic)
  6. Dr. Wong Bor Chern, Medical Officer (Orthopaedic)
  7. Dr. Kelvin Anak Polycarp, Medical Officer (Paediatric)
  8. Dr. Firdaus Bin Izhar, Medical Officer (Paediatric)
  9. Madam Hasliza Binti Halim, Study Coordinator
  10. Madam Law Yen Sin, Pharmacist
  11. Miss Nor Suhada Binti Sooaid, Pharmacist
  12. Mr. Amme Bin Ammeran, Microbiologist
  13. Mr. Mohamad Raheimi Bin Md Saad, Microbiologist
  14. Staff nurses from Kenanga 6

 

 

References:

  1. Howard-Jones, A.R., Isaacs, D.Systematic review of duration and choice of systemic antibiotics therapy for acute haematogenous bacterial osteomyelitis in children. J. Paediatr. ChildHealth. 2013;49:760–768.
  2. Yeo,A.,Ramachandran,M.Acutehaematogenousosteomyelitisinchildren.BMJ 2014;348:66.
  3. KrogstadP.Osteomyelitis.In: FeiginRD,CherryJD, Demmler-HarrisonGD,KaplanSL, editors.TextbookofPaediatricInfectiousDiseases.6thEdition.PA,USA:Saunders Elsevier;2009.pp.725–742.
  4. Pääkkönen,M.,Peltola,H.Boneandjointinfections.Pediatr.Clin.N.Am.2013;60: 425–436.
  5. Chiappini E,  Camposampiero  C, Lazzeri S,  Indolfi G,  De Martino  M, Galli  L. Epidemiology andManagementofAcuteHaematogenousOsteomyelitisinaTertiary Paediatric Center. International Journal of Environmental Research and Public Health. 2017;14(5):477.
  6. Street, M., Puna, R., Huang, M., Crawford, H.Paediatric acute hematogenous osteomyelitis. Journal of Paediatric Orthopaedics. 2015; 35 (6):634-9.