Each year the Society for Clinical Trials presents an award to the randomized clinical trial published (either electronically or in print) in the previous year that best fulfills the following standards:
- It improves the lot of humankind.
- It provides the basis for a substantial, beneficial change in health care.
- It reflects expertise in subject matter, excellence in methodology, and concern for study participants.
- It overcomes obstacles in implementation.
- The presentation of its design, execution, and results is a model of clarity and intellectual soundness.
TRIAL OF THE YEAR 2012:
The Maternal-Fetal Surgery For Myelomeningocele Trial (MOMS)
The award for 2012 was presented by Catherine Spong, Elizabeth Thom and Jody Farrell at SCT’s 33rd Annual Meeting in Miami. Published in The New England Journal of Medicine in March 2011 (N Engl J Med 2011;364:993-1004).
The MOMS trial compared prenatal versus postnatal surgery for myelomeningocele (spina bifida). The trial was stopped because of superior results with the prenatal surgery after 183 patients had been enrolled (out of a planned 200). The primary outcome of fetal or neonatal death or the need for placement of a cerebrospinal shunt by one year of age occurred in 68% of those undergoing prenatal surgery and 98% of those undergoing postnatal surgery.
The MOMS trial faced great difficulties in recruiting women who had recently received a devastating diagnosis, entailing counseling and providing considerable information and resources about options and ethical considerations. Those randomized to prenatal surgery needed to remain close to the participating clinical center. The effort required to overcome the many obstacles in the conduct of this important trial was a key factor in its selection as Trial of the Year.
Fig: Mitka et al. JAMA 2012
Determining the sample of participants to be analysed is a crucial step in reporting clinical trials. For such analyses, the gold standard is the “intention-to-treat” principle.
Intention-to-treat analysis is a comparison of the treatment groups that includes all patients as originally allocated after randomization. This is the recommended method in superiority trials to avoid any bias.
- Retains balance in prognostic factors arising from the original random treatment allocation
- Gives an unbiased estimate of treatment effect
- Admits non-compliance and protocol deviations, thus reflecting a real clinical situation
Requirements for an ideal ITT analysis
- Full compliance with randomised treatment
- No missing responses
- Follow-up on all participants
- Estimate of treatment effect is generally conservative because of dilution due to non-compliance
- In equivalence trials (attempting to prove that two treatments do not differ by more than a certain amount), this analysis will favour equality of treatments
- Interpretation becomes difficult if a large proportion of participants cross over to opposite treatment arms
- Full application of intention to treat is possible only when complete outcome data are available for all randomised subjects
Application of ITT Analysis in clinical trials:
- About half of all published reports of randomised controlled trials stated that intention to treat was used, but handling of deviations from randomised allocation varied widely.
- Many trials had some missing data on the primary outcome variable, and methods used to deal with this were generally inadequate, potentially leading to bias.
- Intention to treat analyses are often inadequately described and inadequately applied.
Several steps have been taken by the Government, as follows, to strengthen the clinical trial approval procedures and their monitoring mechanism to ensure that safety, rights and well-being of clinical trial subjects are protected:
- 12 New Drug Advisory Committees (NDAC) consisting of leading experts mostly from the Government medical colleges and institutes from all over the country have been constituted to advise the Central Drugs Standard Control Organisation (CDSCO) in matters related to approval of clinical trials and new drugs. Fresh applications of clinical trial proposals of new drug substances excluding investigational new drugs (INDs) are being evaluated by these Committees.
- For INDs, two separate expert committees have similarly been constituted. Applications of Investigational New Drugs (IND) i.e., New Drug Substances which have never earlier been used in human beings are evaluated by an IND Committee, chaired by the Director General, Indian Council of Medical Research (ICMR). Similarly, for medical devices, six Medical Device Advisory Committees (MDAC) have been constituted.
- Registration of clinical trial in ICMR’s registry at http://www.ctri.in has been made mandatory.
- Guidelines for conducting inspection of clinical trial sites and sponsor / Clinical Research Organizations (CROs) have been prepared.
- Proposals to amend the toxicity study data requirements for approval of clinical trial / new drugs to make it harmonized with the international guidelines have been approved by Drugs Technical Advisory Board (DTAB).
- It has been made mandatory that Ethical Review Boards across the country are registered with the CDSCO and follow regulations laid down by the DCGI’s Office.
- GCP Guidelines for Clinical Trials in ASU (Ayurveda, Siddha, Unani) (auroushealthcare.wordpress.com)
- Why we need smarter clinical trials for cancer treatments (instituteofcancerresearch.wordpress.com)
- Videorecording of consent for clinical trials mandatory (thehindu.com)
Scientists have created a novel transparent skull implant, which may give neurosurgeons a “window to the brain,” according to a study published in the journal Nanomedicine: Nanotechnology, Biology and Medicine.
Researchers from the University of California, Riverside, say they hope the implant will lead to new treatment strategies for those with life-threatening neurological disorders, such as traumatic brain injury and brain cancer.
At present, the majority of neurological procedures involve craniectomies. A craniectomy is a neurosurgical procedure where a part of the skull is removed to give swelling in the brain room to expand.
Laser-based treatments have shown promise for many brain disorders in the past, but most medical lasers are unable to penetrate through the skull. Therefore, the scientists hope this novel implant will take laser-based neurological treatments to the next level.
The department of AYUSH has issued good clinical practice (GCP) guidelines for clinical trials in Ayurveda, Siddha and Unani (ASU) medicines which will facilitate the researchers and institutions in adopting a standard way of good clinical practice while conducting the ASU clinicaltrials.
The guidelines are addressed to investigators and all those, who are interested, concerned, involved and affected with the conduct of clinical trials on ASU drugs. These are timely in view of the focus being given for scientific validation and for promoting evidence-based use of ASU treatments and are meant for voluntary use, not linked with any provisions of Drugs & Cosmetics (D&C) Act, 1940, and the rules there under.
Good Clinical Practice is a set of guidelines which encompasses the design, conduct, termination, audit, analysis, reporting and documentation of the studies involving human subjects. The fundamental tenet of GCP is that in research on man, the interest of science and society should never take precedence over considerations related to the well being of the study subject. It aims to ensure that the studies are scientifically and ethically sound and that the clinical properties of the ASU medicine under investigation are properly documented.
The guidelines seek to establish two cardinal principles: protection of the rights of human subjects and authenticity of ASU medicine clinical trial data generated. These guidelines are formulated based on CDSCO Document on GCP Guidelines (2001) for Clinical Trials on Pharmaceutical Products. They should be followed for carrying out all ASU medicine research in India at all stages of drug development, whether prior or subsequent to product registration in India.
2. Pre-requisites for the study
4. Record Keeping and Data Handling
5. Quality Assurance
7. Special Concerns
Appendix I : Guidelines for Evaluation of Ayurveda, Siddha and Unani Medicine
Appendix II : Ethical Issues (Ethical Guidelines for Biomedical Research Human Participants, Indian Council of Medical Research 2006
Appendix III : Investigator’s Brochure
Appendix IV : Essential Documents
Download the GCP -ASU from here http://indianmedicine.nic.in/writereaddata/linkimages/5110899178-Final%20Book%2028-03-13.pdf